Lenard A Adler, M.D.

Optimizing Clinical Outcomes Across Domains of Life in Adolescents and Adults With ADHD
Adler, Lenard A.; Mattingly, Gregory W.; Montano, C. Brendan; Newcorn, Jeffrey H.
2011 JUL ;72(7):1008-1014, Journal of clinical psychiatry
— id: 137032, year: 2011, vol: 72, page: 1008, stat: Journal Article,

Performance improvement CME: adult ADHD
Adler, Lenard A; Barkley, Russell A; Newcorn, Jeffrey H
2011 Apr;72(4):e15-e15, Journal of clinical psychiatry
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders and is now understood to be a lifelong condition for most individuals. Unfortunately, many adults with ADHD are not being diagnosed, possibly due to insufficient diagnostic criteria, the complex presentation of the disorder, and a reluctance by physicians to diagnose the disorder in adults. Additionally, many of those who have been diagnosed with ADHD do not receive adequate treatment despite the availability of established and effective agents. Performance Improvement CME (PI CME) is an educational activity in which clinicians retrospectively assess their current clinical practice, choose areas for improvement and implement interventions based on treatment guidelines and health care standards, and then re-evaluate their clinical practice to assess the improvements made. This PI CME activity focuses on improving the diagnosis and treatment of adult ADHD
— id: 131964, year: 2011, vol: 72, page: e15, stat: Journal Article,

Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study
Adler, Lenard A; Lynch, Lauren R; Shaw, David M; Wallace, Samantha P; Ciranni, Michael A; Briggie, Alexis M; Kulaga, Agatha; O'Donnell, Katherine E; Faraone, Stephen V
2011 Sep;123(5):71-79, Postgraduate medicine
Objectives: The study objectives were to 1) evaluate medication adherence for adults with attention-deficit/hyperactivity disorder (ADHD) treated with 3 times daily (TID) mixed amphetamine salts immediate release (MAS IR) versus once-daily (qAM) MAS extended release (MAS XR) in a randomized, crossover study; and 2) to examine the associations between adherence and efficacy for MAS IR and MAS XR. Methods: Sixty-two adults with ADHD were enrolled and 49 completed the study. The treatment condition order (TID-qAM or qAM-TID) was counterbalanced across participants, with an intervening washout period of >/= 7 days. Adherence was assessed via 3 measures: 1) self-report, 2) pill count, and 3) the Medication Event Monitoring System (MEMS((R))). The primary efficacy measure was the ADHD Rating Scale (ADHD-RS); secondary measures included the Time-Sensitive ADHD Symptom Scale (TASS) and Clinical Global Impressions-Severity of Illness (CGI-S) scale. Results: Adherence to treatment as measured by self-report and pill count was not significantly different between MAS XR and MAS IR. Adherence was significantly better for MAS XR than MAS IR for all of the MEMS((R)) measures. The mean change in ADHD-RS, TASS, and CGI-S scores at endpoint was significantly improved for both MAS IR and MAS XR and did not differ significantly between groups. There was not a significant adherence by efficacy interaction. Conclusion: Adults with ADHD adhered equally well with MAS IR as with MAS XR when assessed by pill count and self-report, but not by the MEMS((R)) measures. Both treatments significantly reduced ADHD symptoms, and efficacy was not significantly different between groups. Adherence was not associated with treatment outcome
— id: 137448, year: 2011, vol: 123, page: 71, stat: Journal Article,

Administering and evaluating the results of the adult ADHD Self-Report Scale (ASRS) in adolescents
Adler, Lenard A; Newcorn, Jeffrey H
2011 Jun;72(6):e20-e20, Journal of clinical psychiatry
Attention-deficit/hyperactivity disorder (ADHD) is a common condition that can be difficult to diagnose in adolescents, since symptoms may vary among patients, evolve over time, and mimic symptoms of other disorders. Various rating scales are helpful to the clinician when evaluating patients for ADHD and should be used as part of a thorough assessment. Clinicians should use both informant- and self-report rating scales to gather as much information as possible, while being aware that informants are subject to rater error and adolescents typically underreport symptoms. Rating scales can establish a baseline measure of the patient's symptom type and frequency, provide a framework for assessing symptom impairment, and aid clinicians in monitoring treatment response. The Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist is a reliable self-report rating scale for adolescents as well as adults
— id: 134928, year: 2011, vol: 72, page: e20, stat: Journal Article,

Assessing adolescents using ADHD rating scales
Adler, Lenard A; Newcorn, Jeffrey H
2011 May;72(5):e17-e17, Journal of clinical psychiatry
Children with ADHD will often continue to have the disorder through adolescence, although individual symptoms may lessen or change, so their symptoms will need to be reassessed over time. In addition, adolescence is a transitional period in which youths experience new tasks and developmental challenges that may reveal impairments due to ADHD that were not apparent earlier. Evaluating for ADHD can be complicated by the differing symptoms seen in adolescents compared with children and the difficulty in obtaining a longitudinal history of symptoms. Various rating scales are available that can help clinicians to evaluate symptom frequency and severity and establish impairment when diagnosing adolescents with ADHD. Rating scales are also useful for establishing a baseline for symptoms, delineating individual symptoms as treatment targets, and measuring treatment success in patients with ADHD
— id: 134455, year: 2011, vol: 72, page: e17, stat: Journal Article,

Long-Term Safety of OROS Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder: An Open-Label, Dose-Titration, 1-Year Study
Adler, Lenard A; Orman, Camille; Starr, H Lynn; Silber, Steve; Palumbo, Joseph; Cooper, Kimberly; Berwaerts, Joris; Harrison, Diane D
2011 Feb;31(1):108-114, Journal of clinical psychopharmacology
OBJECTIVE: : To evaluate the long-term safety of OROS methylphenidate in the management of attention-deficit/hyperactivity disorder (ADHD) in adults. METHODS: : This multicenter, open-label, dose-titration, flexible dose study enrolled adults with ADHD for 6 or 12 months of treatment with OROS methylphenidate. Dosing began at 36 mg/d, with titration in 18-mg increments every 7 days until a predefined outcome (efficacy threshold, maximum dosage of 108 mg/d, or limiting adverse event). Dose reduction occurred for prespecified reasons, and the subjects discontinued if unable to tolerate 36 mg/d. Assessments included ADHD symptoms, adverse events, vital signs, and laboratory results. RESULTS: : A total of 550 subjects received treatment (52% were men; mean age, 39 years; range, 18-65 years), and 57% (146/258) and 44% (129/292) completed their 6 or 12 months of treatment with mean durations of 128 and 213 days, respectively. The final prescribed dosages were 36 mg/d (22.4%), 54 mg/d (25.1%), 72 mg/d (22.0%), 90 mg/d (17.1%), and 108 mg/d (13.5%). Modest increases from baseline to final visit were observed in mean systolic (2.6 mm Hg) and diastolic (1.9 mm Hg) blood pressure and pulse (4.1 beats per minute). The mean weight decreased by 2.3 kg. No clinically meaningful changes in laboratory values or electrocardiogram parameters were observed other than increased heart rate. Most common adverse events included decreased appetite (26.7%), headache (24.0%), and insomnia (20.7%). No serious adverse event was considered related to study medication. Several measures of efficacy indicated improvement during the study. CONCLUSIONS: : OROS methylphenidate, in the flexible dosage range from 36 to 108 mg/d, was well tolerated for up to 1 year in adults with ADHD
— id: 117350, year: 2011, vol: 31, page: 108, stat: Journal Article,

Preliminary reliability and validity of a new time-sensitive ADHD symptom scale in adolescents with ADHD
Adler, Lenard A; Shaw, David M; Spencer, Thomas J; Newcorn, Jeffrey H; Sitt, David J; Minerly, Anachristina E; Davidow, Jennifer V; Faraone, Stephen V
2011 Sep;123(5):7-13, Postgraduate medicine
Objectives: To validate the Time-Sensitive ADHD Symptom Scale (TASS) in the assessment of symptom change during the day in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 40 participants with ADHD aged 13 to 17 years completed 1 or 2 visits, 1 to 9 weeks apart. The TASS and the ADHD Rating Scale-IV (ADHD-RS-IV) were completed twice at each visit: at the time of the clinic visit (in-clinic assessment) and 2 to 6 hours afterwards (evening assessment). Results: Internal consistency of the TASS was high, with Cronbach's alpha coefficients of 0.91 (in-clinic) and 0.90 (evening) for visit 1, and 0.88 (in-clinic) and 0.86 (evening) for visit 2. Pearson's correlation coefficients between the TASS and ADHD-RS-IV were significant at both visits (P < 0.0001). Stability analyses of the TASS found no significant effect between ratings performed at different visits (P = 0.936), but there was a significant effect of the assessment time within visits (P < 0.0001). There was not a significant visit by assessment time interaction (P = 0.924). Conclusions: The TASS showed high internal consistency and high concurrent validity with the ADHD-RS-IV. Results of this preliminary study indicate that the TASS is a valid and reliable self-report scale for adolescents with ADHD
— id: 137447, year: 2011, vol: 123, page: 7, stat: Journal Article,

Reliability and validity of the Time-Sensitive ADHD Symptom Scale in adults
Adler, Lenard A; Shaw, David M; Spencer, Thomas J; Newcorn, Jeffrey H; Sitt, David J; Morrill, Melinda; Davidow, Jennifer V; Glatt, Stephen J; Faraone, Stephen V
2011 Nov;52(6):769-773, Comprehensive psychiatry
OBJECTIVES: The objective of this study was to examine the psychometric properties of the Time-Sensitive ADHD Symptom Scale (TASS) to evaluate change of attention-deficit/hyperactivity disorder (ADHD) symptoms over the course of a day in adults. METHODS: Eighty adults with ADHD participated in 1 or 2 visits, 1 to 9 weeks apart. At each visit, participants completed the TASS followed by raters administering the ADHD Rating Scale (ADHD-RS). Additional TASS and ADHD-RS ratings were completed 2 to 6 hours after each visit via telephone. Internal consistency of TASS items was assessed by Cronbach's alpha. Convergent validity of TASS and ADHD-RS total mean item scores was assessed using Pearson's correlation coefficients. kappa correlations were calculated to assess item-by-item reliability between TASS and ADHD-RS items. RESULTS: Internal consistency of TASS items was high, with an overall Cronbach's alpha coefficient of .93. The Pearson's correlation coefficient between the TASS and ADHD-RS was significant for all visits (r = 0.70, P < .0001). There was moderate agreement between individual items on the TASS and ADHD-RS, with significant kappa coefficients for almost all items (P < .05). DISCUSSION: The TASS showed high internal consistency and concurrent validity with the clinician-administered ADHD-RS and is a valid and reliable scale for measuring change in ADHD symptoms over the course of a day in adults
— id: 139468, year: 2011, vol: 52, page: 769, stat: Journal Article,

Efficacy and safety of the novel alpha(4)beta (2) neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study
Apostol G; Abi-Saab W; Kratochvil CJ; Adler LA; Robieson WZ; Gault LM; Pritchett YL; Feifel D; Collins MA; Saltarelli MD
2011 Feb;219(3):715-725, Psychopharmacology
RATIONALE: alpha(4)beta(2) Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). OBJECTIVES: This study examined the efficacy and safety of the alpha(4)beta(2) NNR partial agonist ABT-089 versus placebo in adults with ADHD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled crossover study, subjects received placebo followed by ABT-089 (2 mg once daily [QD], 5 mg QD, 15 mg QD, 40 mg QD, or 40 mg twice daily [BID]), or vice versa, in a 2 x 2 crossover design. Each treatment period was 4 weeks, separated by a 2-week washout period. The primary efficacy endpoint was the Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS:Inv) total score at the end of each treatment period. Secondary outcomes based on clinician- and self-rated efficacy scales were evaluated. RESULTS: Of the 221 subjects enrolled, 171 met criteria for inclusion in the completers dataset for efficacy analyses. ABT-089 was superior to placebo on the CAARS:Inv total score at 40 mg QD and 40 mg BID (model-based least square mean difference from placebo: -4.33, P = 0.02; -3.02, P = 0.03, respectively). ABT-089 also demonstrated significant improvements on several secondary measures of efficacy. ABT-089 was generally safe and well tolerated. The most commonly reported adverse events (>/=5%) for total ABT-089-treated subjects at rates higher than placebo were headache, upper respiratory tract infection, irritability, insomnia, and nasopharyngitis. CONCLUSIONS: In this phase 2 crossover study, the NNR partial agonist ABT-089, at doses of 40 mg QD and 40 mg BID, was efficacious and generally well tolerated in treatment of adults with ADHD
— id: 147208, year: 2011, vol: 219, page: 715, stat: Journal Article,

Effect of atomoxetine on executive function impairments in adults with ADHD
Brown, Thomas E; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W; Padival, Anoop K; Schuh, Kory; Trzepacz, Paula T; Kelsey, Douglas
2011 Feb;15(2):130-138, Journal of attention disorders
OBJECTIVE: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. METHOD: In a randomized, double-blind clinical trial, adults with ADHD received either atomoxetine 25 to 100 mg/day or placebo for 6 months. Patients completed the BADDS to report their current daily functioning in 5 clusters of ADHD-related impairments of executive functioning: (1) Organizing and Activating to Work; (2) Focusing for Tasks; (3) Regulating Alertness and Effort; (4) Modulating Emotions; and (5) Utilizing Working Memory. RESULTS: Mean scores were significantly more improved in the atomoxetine group compared to the placebo group: total score, -27.0 versus -19.0 (p < .001); all 5 cluster scores, p < .01. CONCLUSIONS: Once-daily atomoxetine can improve executive function impairments in adults with ADHD as assessed by the BADDS
— id: 138354, year: 2011, vol: 15, page: 130, stat: Journal Article,

An exploration of site effects in a multisite trial of OROS-methylphenidate for smokers with attention deficit/hyperactivity disorder
Covey, Lirio S; Hu, Mei-Chen; Green, Carla A; Brigham, Gregory; Hurt, Richard D; Adler, Lenard; Winhusen, Theresa
2011 Sep;37(5):392-399, American journal of drug & alcohol abuse
BACKGROUND: Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). OBJECTIVE: Analysis was conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms and smoking cessation rates, and the effect of treatment on these outcomes would differ by type of site. METHOD: A total of 255 adult smokers diagnosed with ADHD were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and 104 in the mental health clinics. RESULTS: The three site-types were similar in demographic characteristics, smoking history, baseline level of ADHD symptoms, and history of psychiatric illness. Site-type but not a site-type by treatment interaction predicted prolonged smoking abstinence. A significant three-way interaction of site-type, treatment, and time-predicted improvement in ADHD symptoms. Moderate to strong effects of OROS-MPH relative to placebo were observed in the mental health and the ADHD clinics; a weak effect was observed in the tobacco dependence clinics. CONCLUSION: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. SCIENTIFIC SIGNIFICANCE: Assessment of site-type effects can indicate the generalizability of findings from multisite trials and should be routinely incorporated in the design of multisite trials
— id: 147207, year: 2011, vol: 37, page: 392, stat: Journal Article,

Divergence by ADHD subtype in smoking cessation response to OROS-methylphenidate
Covey, Lirio S; Hu, Mei-Chen; Weissman, Judith; Croghan, Ivana; Adler, Lenard; Winhusen, Theresa
2011 Oct;13(10):1003-1008, Nicotine & tobacco research
INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition subclassified in DSM-IV according to its core symptoms domains as (a) predominantly inattentive (ADHD-IN), (b) predominantly hyperactive/impulsive (ADHD-H), and (c) combined inattentive and hyperactive/impulsive (ADHD-C). Whether these subtypes represent distinct clinical entities or points on a severity continuum is controversial. Divergence in treatment response is a potential indicator of qualitative heterogeneity. This study examined smoking cessation response by ADHD subtype to osmotic-release oral system methylphenidate (OROS-MPH). METHODS: Male and female adult smokers (ADHD-C = 167 and ADHD-IN = 87) were randomized to receive OROS-MPH or placebo as augmentation treatment to nicotine patch and counseling. Logistic regression was conducted to test the effect of OROS-MPH versus placebo on prolonged smoking abstinence by ADHD subtype. RESULTS: The subtypes were similar in baseline demographic, smoking, and psychiatric history but differed in smoking cessation response to OROS-MPH or placebo as a function of nicotine dependence level. The 3-way interaction was significant; chi(2)(1) = 8.22, p < .01. Among highly dependent smokers, the prolonged abstinence rates were greater with OROS-MPH than with placebo in the ADHD-C group (60% vs. 31.3%, respectively, p < .05) but higher with placebo than with OROS-MPH in the ADHD-IN group (60% vs. 11.8%, respectively, p < .01). Abstinence rates did not differ by subtype or treatment among smokers who were less nicotine dependent. Conclusion: Contrasting treatment response and divergence in the impact of nicotine dependence level support the hypothesis of ADHD subtypes as distinct clinical entities and may indicate the need and directions for personalized targeted treatments of smokers with ADHD
— id: 147209, year: 2011, vol: 13, page: 1003, stat: Journal Article,

Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity
Ginsberg, Lawrence; Katic, Alain; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Lasser, Robert; Scheckner, Brian; Adler, Lenard A
2011 Jun;27(6):1097-1107, Current medical research & opinon
Abstract Objective: To examine the impact of baseline severity on lisdexamfetamine dimesylate (LDX) efficacy in a long-term study of adults with attention-deficit/hyperactivity disorder (ADHD). Research design and methods: Adults from a 4-week, placebo-controlled, forced dose-escalation study with LDX (30-70 mg/day) or placebo were enrolled in a long-term, open-label dose-optimization study for an additional 12 months. In post hoc analyses, participants were stratified by baseline severity (from the prior short-term study) with Clinical Global Impressions-Severity (CGI-S) scores of 4 (moderately), 5 (markedly), or >/=6 (severely/extremely ill). ADHD-Rating Scale IV (ADHD-RS-IV) with adult prompts (primary) and CGI-Improvement (CGI-I) were used to assess effectiveness. Clinical response was defined as a >/=30% decrease in ADHD-RS-IV from baseline and a CGI-I of 1 or 2; symptomatic remission was defined as ADHD-RS-IV </=18. Treatment-emergent adverse events (TEAEs) were monitored. Results: Participants had baseline CGI-S scores of 4 (n = 114), 5 (n = 188), or >/=6 (n = 43). At endpoint, mean (SD) change from baseline in ADHD-RS-IV was greater (p < 0.0001) for participants with CGI-S = 5 (-26.4 [11.77]) and >/=6 (-32.3 [9.81]) than for participants with CGI-S = 4 (-19.5 [9.97]). At endpoint, 81.6%, 84.6%, and 88.4% of participants were very much/much improved (CGI-I of 1 or 2) in CGI-S categories of 4, 5, and >/=6, respectively. Clinical response criteria were met by 78.9%, 83.5%, and 88.4% and symptomatic remission criteria by 64.0%, 65.4%, and 72.1% of participants with CGI-S = 4, 5, and >/=6, respectively. The most frequently reported TEAEs with participant incidence >/=10% for any LDX dose were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Conclusions: Some aspects of these analyses (e.g., open-label design without placebo control, inclusion and exclusion criteria of the demographic profile of participants, and the post hoc nature of the statistical analysis) limit interpretation. However, long-term LDX treatment demonstrated increased degree of symptom improvement with greater baseline symptom severity. Rates of clinical response and symptomatic remission tended to be greater for those with greater baseline severity. LDX demonstrated a safety profile consistent with long-acting stimulant use
— id: 134196, year: 2011, vol: 27, page: 1097, stat: Journal Article,

PDI-4A: an augmented provisional screening instrument assessing 5 additional common anxiety-related diagnoses in adult primary care patients
Houston, John P; Kroenke, Kurt; Davidson, Jonathan R; Adler, Lenard A; Faries, Douglas E; Ahl, Jonna; Swindle, Ralph; Trzepacz, Paula T
2011 Sep;123(5):89-95, Postgraduate medicine
Patients with nonpsychotic mental health and emotional problems are commonly seen by primary care physicians. The objective of this study was to expand the Provisional Diagnostic Instrument-4 (PDI-4) to include a short self-report screen for 5 common anxiety-related diagnoses: panic attack (PA), social phobia (SP), obsessive-compulsive disorder (OCD), hypochondriasis, and post-traumatic stress disorder (PTSD). Primary care patients (N = 343) were originally evaluated with a self-report screen comprised of 85 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptom-based candidate questions, then interviewed by a trained rater for Structured Clinical Interview Research Version (SCID)/Adult ADHD Clinician Diagnostic Scale version 1.2 (ACDS) assessment and diagnosis. Responses to screening questions were used to calculate sensitivity and specificity for an SCID diagnosis, and to select the optimal cutoffs in symptom frequency for 1 or 2 questions for each additional anxiety-related diagnosis. The PDI-4 Anxiety (PDI-4A) contains 6 items for provisional differential diagnosis of PA, SP, OCD, hypochondriasis, and PTSD in addition to items for the PDI-4. Sensitivities/specificities were: PA, 88%/68%; SP, 57%/70%; OCD, 88%/61%; hypochondriasis, 67%/85%; and PTSD, 71%/72%. Screening for multiple common anxiety diagnoses may be desirable, although limitations may include reduced sensitivity and specificity for selected diagnoses. The PDI-4A may additionally help primary care physicians identify patients with PA, SP, OCD, hypochondriasis, and PTSD
— id: 137973, year: 2011, vol: 123, page: 89, stat: Journal Article,

A provisional screening instrument for four common mental disorders in adult primary care patients
Houston, John P; Kroenke, Kurt; Faries, Douglas E; Doebbeling, Caroline Carney; Adler, Lenard A; Ahl, Jonna; Swindle, Ralph; Trzepacz, Paula T
2011 Jan-Feb;52(1):48-55, Psychosomatics
OBJECTIVE: To develop an adult self-report instrument for provisional diagnosis of four common mental disorders in primary care patients. METHODS: Primary care patients were evaluated during routine clinic visits with a self-report screening tool comprised of 85 DSM-IV symptom-based candidate questions. Patients with a physician-assessed provisional diagnosis for generalized anxiety disorder (GAD), major depressive episode (MDE), past/present mania, and adult attention-deficit/hyperactivity disorder (ADHD), or none of these, completed additional self-report clinical questionnaires, and then were interviewed on the telephone by a trained rater for a SCID/ACDS diagnosis. Responses to the symptom-based candidate questions were used to calculate sensitivity and specificity for a SCID/ACDS diagnosis (GAD, N = 24; MDE, N = 89; Mania, N = 24; ADHD, N = 65) and to select the optimal four questions for each diagnosis to be included in the instrument. RESULTS: Analyses resulted in a 17-item instrument for provisional differential diagnosis of GAD, MDE, past/present mania, and ADHD. Comparison of limited symptom-based versus full DSM-IV criteria-based diagnosis showed minimal differences for relative diagnostic accuracy. Sensitivities and specificities, respectively, were 83% and 75% for GAD, 80% and 80% for MDE, 83% and 82% for mania, and 82%and 73% for ADHD. CONCLUSIONS: Based on this preliminary work, the Provisional Diagnostic Instrument-4 is a brief, easily scored, self-report instrument that may assist primary care physicians to identify potential cases of GAD, MDE, past/present mania, and ADHD
— id: 134291, year: 2011, vol: 52, page: 48, stat: Journal Article,

A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults With ADHD
Rivkin A; Alexander RC; Knighton J; Hutson PH; Wang XJ; Snavely DB; Rosah T; Watt AP; Reimherr FW; Adler LA
2011 Nov 16;:?-? #, Journal of attention disorders
Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted in adults with primary ADHD. The primary end point was changed from baseline in total score on the Adult ADHD Investigator Symptom Rating Scale following a 4-week treatment regimen. Additional measures included Clinical Global Impression-Severity Scale, Hospital Anxiety and Depression Scale, and Brown Attention Deficit Disorder Scale and D4 genotype analysis. Results: No statistically significant treatment differences were found between MK-0929 and placebo in any of the primary or secondary assessments. Conclusion: Results from this study suggest that blockade of the D4 receptor alone is not efficacious in the treatment of adult ADHD. (J. of Att. Dis. 2011; XX(X) 1-XX)
— id: 147204, year: 2011, vol: , page: ?, stat: Journal Article,

Correlates of Alcohol Use in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Alcohol Use Disorders
Wilens, Timothy E.; Adler, Lenard A.; Tanaka, Yoko; Xiao, Feng; D'Souza, Deborah N.; Gutkin, Stephen W.; Upadhyaya, Himanshu P.
2011 JUL-AUG ;20(4):375-376, American journal on addictions
— id: 134905, year: 2011, vol: 20, page: 375, stat: Journal Article,

Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine
Wilens, Timothy E; Adler, Lenard A; Tanaka, Yoko; Xiao, Feng; D'Souza, Deborah N; Gutkin, Stephen W; Upadhyaya, Himanshu P
2011 Dec;27(12):2309-2320, Current medical research & opinon
Abstract Background: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied. Objective: To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults. Methods: Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale. Results: Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 - 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 -0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each). Conclusions: No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. Trial Registration (base study): ClinicalTrials.gov Identifier: NCT00190957
— id: 147206, year: 2011, vol: 27, page: 2309, stat: Journal Article,

Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder
Winhusen, Theresa M; Lewis, Daniel F; Riggs, Paula D; Davies, Robert D; Adler, Lenard A; Sonne, Susan; Somoza, Eugene C
2011 Oct;21(5):455-463, Journal of child & adolescent psychopharmacology
OBJECTIVE: Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. METHOD: Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). RESULTS: Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. CONCLUSIONS: With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence
— id: 147205, year: 2011, vol: 21, page: 455, stat: Journal Article,

ADHD screening and follow-up: Results from a survey of participants 2 years after an adult ADHD screening day
Adler L.A.; Ciranni M.; Shaw D.M.; Paunikar P.
2010 ;17(2):32-37, Primary Psychiatry
Background: This study evaluated participants 2 years after they had screened positive on the Adult ADHD Self-Report Scale version 1.1 (ASRS v 1.1) Screener for attention-deficit hyperactivity disorder (ADHD) at a screening day event to assess their clinical course in terms of a formal ADHD diagnosis and treatment. Methods: Fifty-one of the 228 participants who initially screened positive and consented to future contact for research were randomly selected to participate in a telephone survey. Results: Only 20 of the 41 participants with no prior ADHD diagnosis followed up to seek a formal diagnosis. ADHD was diagnosed in 90% of those who followed up. Between those who did and did not seek an ADHD diagnosis, there were no differences in the amount of contact with primary care and mental health providers. Discussion: The ASRS v1.1 Screener was effective at identifying individuals at high risk; however, <50% of at-risk individuals followed up for diagnosis. The amount of contact with the healthcare system was comparable between those who did and those who did not seek an ADHD diagnosis, but this regular contact with medical and mental health professionals did not lead to diagnosis and treatment of their symptoms. Conclusion: While screening for adult ADHD can identify adults who might have ADHD, screening alone is not sufficient to ensure subsequent evaluation and treatment. Regular contact with healthcare professionals also does not guarantee that individuals at risk for ADHD will be identified, indicating the need for additional follow-up for individuals who screen positive. copyright MBL Communications Inc
— id: 109195, year: 2010, vol: 17, page: 32, stat: Journal Article,

Open label pilot study of atomoxetine in adults with ADHD and substance use disorder
Adler L.A.; Guida F.; Irons S.; Shaw D.M.
2010 ;6(3-4):196-207, Journal of Dual Diagnosis
OBJECTIVE: The purpose of this 10-week, open-label trial was to evaluate the potential utility of atomoxetine for improving attention-deficit hyperactivity disorder (ADHD) and substance craving in abstinent adults with ADHD who were being treated at a residential treatment facility. METHODS: Eighteen adults were treated with atomoxetine (25-120 mg/day) for up to 10 weeks. Researchers assessed ADHD symptoms with the Adult ADHD Investigator Symptom Rating Scale (AISRS) and substance cravings with the Brief Substance Craving Scale (BSCS). Paired t-tests were used to assess changes in symptoms and craving. RESULTS: Among the 12 participants who completed at least 2 weeks of treatment, mean total AISRS scores improved (43.2 SD 7.4 to 25.8 SD 14.4, t = 5.0, p.001). Participants also reported improvement in some measures of cravings. CONCLUSIONS: These data provide preliminarily support for the utility of atomoxetine in abstinent adults with co-occurring ADHD and substance use disorder.
— id: 120665, year: 2010, vol: 6, page: 196, stat: Journal Article,

Monitoring adults with ADHD: a focus on executive and behavioral function
Adler, Lenard A
2010 Aug;71(8):e18-e18, Journal of clinical psychiatry
Deficits in executive function have been consistently demonstrated in adults with ADHD. Rating scales that measure executive deficits in relation to daily life are useful in assessing ADHD symptoms and in measuring responses to treatment, while neuropsychological testing can measure deficits in executive function that can cause additional impairment in adults with ADHD. Treatments, including psychosocial interventions and stimulant and nonstimulant medications, can be helpful in addressing these executive deficits and the symptoms of adult ADHD
— id: 147210, year: 2010, vol: 71, page: e18, stat: Journal Article,

Atomoxetine Treatment for ADHD: Younger Adults Compared with Older Adults
Durell, Todd; Adler, Lenard; Wilens, Timothy; Paczkowski, Martin; Schuh, Kory
2010 Jan;13(4):401-406, Journal of attention disorders
Objective: Atomoxetine is a nonstimulant medication for treating child, adolescent, and adult ADHD. This meta-analysis compared the effects in younger and older adults. Method: A post hoc analysis was conducted using data from two double-blind, placebo-controlled clinical trials. Data from patients aged 18-25 years were compared with data from patients older than 25 years. Results: In younger adults (mean age = 21.7), atomoxetine produces greater improvement than placebo on the Conners' Adult ADHD Rating Scale's total ADHD symptom score (p = .041, effect size = .797) and the clinical global impressions severity (p = .006, effect size = 1.121). In older adults (mean age = 43.4 years), atomoxetine also produces significant benefit on the CAARS-Inv:SV (p < .001, effect size = .326) and CGI-ADHD-S (p < .001, effect size = .346). The study findings reveal response rates to be 56.4% and 47.8% for the younger and older adults, respectively (p = .188). Tolerability is similar although older adults reported more sexual side effects. Conclusion: Younger and older adults show similar improvements at endpoint. The effect size is higher in younger adults, but this is due primarily to greater variability of response in older patients
— id: 104935, year: 2010, vol: 13, page: 401, stat: Journal Article,

"Interpreting ADHD rating scale scores: Linking ADHD rating scale scores and CGI levels in two randomized controlled trials of lisdexamfetamine dimesylate in ADHD": Erratum
Goodman, David; Faraone, Stephen V; Adler, Lenard A; Dirks, Bryan; Hamdani, Mohamed; Weisler, Richard
2010 ;17(5):18-, Primary Psychiatry
Reports an error in 'Interpreting ADHD Rating Scale Scores: Linking ADHD Rating Scale scores and CGI levels in two randomized controlled trials of lisdexamfetamine dimesylate in ADHD' by David Goodman, Stephen V. Faraone, Lenard A. Adler, Bryan Dirks, Mohamed Hamdani and Richard Weisler (Primary Psychiatry, 2010[Mar], Vol 17[3], 44-52). There was a typographical error on page 47 of the original article. The sentence read: 'Based on the link function from the adult study, baseline ADHD-RS-IV scores ranging from 13.5-7.4 are expected to correspond to CGI-S levels of mildly to moderately ill.' The correct range should be '13.5-37.4' as noted correctly in Table 2 on page 48. (The following abstract of the original article appeared in record 2010-07791-009). Objective: To provide additional understanding of the clinical significance of Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) total and change scores in relation to Clinical Global Impressions-Severity or -Improvement (CGI-S/-I) levels. Methods: Using two similarly designed pivotal trials of lisdexamfetamine dimesylate (Vyvanse, Shire US Inc), equipercentile linking was used to identify scores on the ADHD-RS-IV and CGI that have the same percentile rank. Results: As assessed by CGI-S levels, moderately, markedly, severely, and extremely ill adults had mean (SD) baseline ADHD-RS-IV scores of 36.2 (4.9), 42.1 (6.1), 45.4 (5.1), and 53.0, respectively. A similar relationship was observed in children. At endpoint, children categorized as minimally, much, or very much improved by CGI-I demonstrated mean (SD) ADHD-RS-IV changes from baseline of -9.9 (6.8), -25.5 (7.2), and -33.2 (9.3), respectively. Adults demonstrated a similar relationship between ADHD-RS-IV change scores and CGI-I ratings. Based on equipercentile link function, a change from baseline in ADHD-RS-IV total score of ~10-15 points or 25% to 30% corresponded to a change of 1 level in CGI-I score. Conclusion: This analysis makes possible the establishment of a clinical impression of severity of illness from total ADHD-RS-IV scores and may facilitate the clinical interpretation of improvement of ADHD-RS-IV change scores.
— id: 111394, year: 2010, vol: 17, page: 18, stat: Journal Article,

Interpreting ADHD Rating Scale Scores: Linking ADHD Rating Scale scores and CGI levels in two randomized controlled trials of lisdexamfetamine dimesylate in ADHD
Goodman, David; Faraone, Stephen V; Adler, Lenard A; Dirks, Bryan; Hamdani, Mohamed; Weisler, Richard
2010 ;17(3):44-52, Primary Psychiatry
[Correction Notice: An erratum for this article was reported in Vol 17(5) of Primary Psychiatry (see record 2010-13373-007). There was a typographical error on page 47 of the original article. The sentence read: 'Based on the link function from the adult study, baseline ADHD-RS-IV scores ranging from 13.5-7.4 are expected to correspond to CGI-S levels of mildly to moderately ill.' The correct range should be '13.5-37.4' as noted correctly in Table 2 on page 48.] Objective: To provide additional understanding of the clinical significance of Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) total and change scores in relation to Clinical Global Impressions-Severity or -Improvement (CGI-S/-I) levels. Methods: Using two similarly designed pivotal trials of lisdexamfetamine dimesylate (Vyvanse, Shire US Inc), equipercentile linking was used to identify scores on the ADHD-RS-IV and CGI that have the same percentile rank. Results: As assessed by CGI-S levels, moderately, markedly, severely, and extremely ill adults had mean (SD) baseline ADHD-RS-IV scores of 36.2 (4.9), 42.1 (6.1), 45.4 (5.1), and 53.0, respectively. A similar relationship was observed in children. At endpoint, children categorized as minimally, much, or very much improved by CGI-I demonstrated mean (SD) ADHD-RS-IV changes from baseline of -9.9 (6.8), -25.5 (7.2), and -33.2 (9.3), respectively. Adults demonstrated a similar relationship between ADHD-RS-IV change scores and CGI-I ratings. Based on equipercentile link function, a change from baseline in ADHD-RS-IV total score of ~10-15 points or 25% to 30% corresponded to a change of 1 level in CGI-I score. Conclusion: This analysis makes possible the establishment of a clinical impression of severity of illness from total ADHD-RS-IV scores and may facilitate the clinical interpretation of improvement of ADHD-RS-IV change scores.
— id: 111534, year: 2010, vol: 17, page: 44, stat: Journal Article,

Effects of the Histamine Inverse Agonist MK-0249 in Adult Attention Deficit Disorder: A Randomized, Controlled, Crossover Study
Herring, WJ; Adler, LA; Baranak, CC; Liu, K; Snavely, D; Michelson, D
2010 MAY 1 ;67(9):217S-217S, Biological psychiatry
— id: 111943, year: 2010, vol: 67, page: 217S, stat: Journal Article,

Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale
Kessler, Ronald C; Green, Jennifer Greif; Adler, Lenard A; Barkley, Russell A; Chatterji, Somnath; Faraone, Stephen V; Finkelman, Matthew; Greenhill, Laurence L; Gruber, Michael J; Jewell, Mark; Russo, Leo J; Sampson, Nancy A; Van Brunt, David L
2010 Nov;67(11):1168-1178, Archives of general psychiatry
CONTEXT: Controversy exists about the appropriate criteria for a diagnosis of adult attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To examine the structure and symptoms most predictive of DSM-IV adult ADHD. DESIGN: The data are from clinical interviews in enriched subsamples of the National Comorbidity Survey Replication (n = 131) and a survey of a large managed health care plan (n = 214). The physician-administered Adult ADHD Clinical Diagnostic Scale (ACDS) was used to assess childhood ADHD and expanded symptoms of current adult ADHD. Analyses examined the stability of symptoms from childhood to adulthood, the structure of adult ADHD, and the adult symptoms most predictive of current clinical diagnoses. SETTING: The ACDS was administered telephonically by clinical research interviewers with extensive experience in the diagnosis and treatment of adult ADHD. PARTICIPANTS: An enriched sample of community respondents. MAIN OUTCOME MEASURE: Diagnoses of DSM-IV /ACDS adult ADHD. RESULTS: Almost half of the respondents (45.7%) who had childhood ADHD continued to meet the full DSM-IV criteria for current adult ADHD, with 94.9% of these patients having current attention-deficit disorder and 34.6% having current hyperactivity disorder. Adult persistence was much greater for inattention than for hyperactivity/impulsivity. Additional respondents met the full criteria for current adult ADHD despite not having met the full childhood criteria. A 3-factor structure of adult symptoms included executive functioning (EF), inattention/hyperactivity, and impulsivity. Stepwise logistic regression found EF problems to be the most consistent and discriminating predictors of adult DSM-IV /ACDS ADHD. CONCLUSIONS: These findings document the greater persistence of inattentive than of hyperactive/impulsive childhood symptoms of ADHD in adulthood but also show that inattention is not specific to ADHD because it is strongly associated with other adult mental disorders. In comparison, EF problems are more specific and consistently important predictors of DSM-IV adult ADHD despite not being in the DSM-IV, suggesting that the number of EF symptoms should be increased in the DSM-V/ICD-11
— id: 138024, year: 2010, vol: 67, page: 1168, stat: Journal Article,

Genetic polymorphisms in the treatment of depression: speculations from an augmentation study using atomoxetine
Reimherr, Frederick; Amsterdam, Jay; Dunner, David; Adler, Lenard; Zhang, Shuyu; Williams, David; Marchant, Barrie; Michelson, David; Nierenberg, Andrew; Schatzberg, Alan; Feldman, Peter
2010 Jan 30;175(1-2):67-73, Psychiatry research
Treatment-resistant depression may be related to polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) or dysregulation of noradrenergic systems. To examine 5-HTTLPR genotypes and responses to treatment, adult patients (N=261) with current major depression and a symptom severity rating > or =8 on the 17-item Hamilton Depression Rating Scale (HAMD(17)) were treated for 8 weeks with open-label sertraline (100-200 mg/d). Patients remaining symptomatic (total score >4, or >1 on any item of the HAMD(17) Maier-Philipp subscale) were randomly assigned to double-blind therapy with sertraline plus either atomoxetine (40-120 mg/d) or placebo for 8 additional weeks. 5-HTTLPR genotype did not predict responses to sertraline monotherapy or discontinuation rates. Among the 138 patients remaining symptomatic after sertraline monotherapy (L/L = 21%, S/L = 50%, S/S = 29%), significantly more S/S-genotype patients achieved remission under combined sertraline/atomoxetine treatment relative to the other genotypes (S/S = 81.8%; non-S/S = 32.7%), but not under sertraline/placebo treatment (S/S = 35.7%; non-S/S = 37.7%). Minor genotypic differences were noted in adverse event profiles. In patients with poor responses to sertraline monotherapy for depression, addition of atomoxetine may improve responses to treatment of depression in S/S-genotyped patients. Although this study is speculative, it represents a pharmacologically and genotypically well-defined patient population
— id: 110416, year: 2010, vol: 175, page: 67, stat: Journal Article,

Validation of the adult ADHD investigator symptom rating scale (AISRS)
Spencer, Thomas J; Adler, Lenard A; Saylor, Keith E; Brown, Thomas E; Holdnack, James A; Schuh, Kory J; Trzepacz, Paula T; Kelsey, Douglas K
2010 Jul;14(1):57-68, Journal of attention disorders
OBJECTIVE: Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS) that measures aspects of ADHD in adults. METHOD: Psychometric properties of the AISRS total and AISRS subscales are analyzed and compared to the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) and the Clinical Global Impression-ADHD-Severity Scale using data from a placebo-controlled 6-month clinical trial of once-daily atomoxetine. RESULTS: The AISRS has high internal consistency, good convergent, and discriminant validities; modest divergent validity; and small ceiling and floor effects (<or=1%). It correlates highly with the CAARS-Inv:SV. Factor analysis confirms 2 AISRS subscales, hyperactivity-impulsive scale and inattention. The AISRS total and AISRS subscales perform stably. All scales demonstrate responsiveness to change with medication. CONCLUSION: The AISRS and its subscales are robust, valid efficacy measures of ADHD symptoms in adult patients. Its anchored items and semistructured interview are advancements over existing scales
— id: 138142, year: 2010, vol: 14, page: 57, stat: Journal Article,

Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial
Winhusen, Theresa M; Somoza, Eugene C; Brigham, Gregory S; Liu, David S; Green, Carla A; Covey, Lirio S; Croghan, Ivana T; Adler, Lenard A; Weiss, Roger D; Leimberger, Jeffrey D; Lewis, Daniel F; Dorer, Emily M
2010 Dec;71(12):1680-1688, Journal of clinical psychiatry
OBJECTIVE: High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotine's amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD. METHOD: A randomized, double-blind, placebo-controlled, 11-week trial with a 1-month follow-up was conducted at 6 clinical sites between December 2005 and January 2008. Adults (aged 18-55 years) meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomly assigned to OROS-MPH titrated to 72 mg/d (n = 127) or placebo (n = 128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/d nicotine patches starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score. RESULTS: Of 255 randomly assigned participants, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (OR = 1.1; 95% CI, 0.63-1.79; P = .81). Relative to placebo, OROS-MPH evidenced a greater reduction in DSM-IV ADHD-RS score (P < .0001) and in cigarettes per day during the post-quit phase (P = .016). Relative to placebo, OROS-MPH increased blood pressure and heart rate to a statistically, but not clinically, significant degree (P < .05); medication discontinuation did not differ significantly between treatments. CONCLUSIONS: Treatment for ADHD did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers. TRIAL REGISTRATION: clinical trials.gov Identifier: NCT00253747
— id: 138092, year: 2010, vol: 71, page: 1680, stat: Journal Article,

Pharmacotherapy for adult ADHD
Adler, Lenard A
2009 May;70(5):e12-e12, Journal of clinical psychiatry
The U.S. Food and Drug Administration has approved 3 medications, atomoxetine and the extended-release formulations of amphetamine salts and dexmethylphenidate, for the treatment of adult attention-deficit hyperactivity disorder (ADHD). Different formulations of the same drugs, as well as other agents and cognitive-behavioral therapy, have been tested to determine efficacy in ADHD alone and in ADHD with comorbid substance use disorders, mood disorders, and anxiety disorders. A deficit in research exists in regard to these comorbidities in adults with ADHD
— id: 100614, year: 2009, vol: 70, page: e12, stat: Journal Article,

ADHD and comorbid disorders in adults
Adler, Lenard A; Barkley, Russell A; Newcorn, Jeffrey H
2009 ;69(8):1328-1335, Journal of clinical psychiatry
In the United States, approximately 4.4% of adults have attention-deficit/ hyperactivity disorder (ADHD), and the average worldwide prevalence in adults is about 3.4%. However, in the United States, only about 1 in 10 adults with ADHD is currently treated specifically for ADHD. Adults with ADHD are likely to have adaptive impairments, evidenced by educational difficulties, a history of erratic employment, relationship and marital difficulties, credit or money problems, driving problems, risky sexual behavior, early parenthood, legal difficulties, poor physical health, and substance abuse problems. The DSM-IV-TR criteria for ADHD were developed for diagnosing children and were not intended for use in adults. To identify symptoms appropriate for ADHD criteria in adults, a study compared the following 3 groups: adults referred to a clinic for ADHD who were subsequently diagnosed with ADHD, a control group of adults referred to the same clinic who thought they had ADHD but did not, and a community control group. ADHD was diagnosed by a structured clinical interview using the DSM-IV-TR criteria but excluding age at onset.
— id: 100653, year: 2009, vol: 69, page: 1328, stat: Journal Article,

Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder
Adler, Lenard A; Goodman, David; Weisler, Richard; Hamdani, Mohamed; Roth, Thomas
2009 ;5:34-34, Behavioral & brain functions : BBF
ABSTRACT: BACKGROUND: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX) on sleep quality in adults with ADHD. METHODS: This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty). RESULTS: The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (P = .19) indicating poor overall sleep quality. At endpoint, least squares (LS) mean change from baseline was -0.8 for LDX vs -0.5 for placebo (P = .33). The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, P = .0001). LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence >/=2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%), initial insomnia (5.0% and 3.2%), middle insomnia (3.6% and 0%), sleep disorder (0.6% and 3.2%), somnolence (0.3% and 3.2%), and fatigue (4.7% and 4.8%), and were generally mild or moderate in severity. CONCLUSION: For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880
— id: 101893, year: 2009, vol: 5, page: 34, stat: Journal Article,

Screening and imputed prevalence of ADHD in adult patients with comorbid substance use disorder at a residential treatment facility
Adler, Lenard A; Guida, Frank; Irons, Shirley; Rotrosen, John; O'Donnell, Katherine
2009 Sep;121(5):7-10, Postgraduate medicine
BACKGROUND: Although attention deficit/hyperactive disorder (ADHD) is a common comorbidity in individuals who are diagnosed with substance use disorder (SUD), little data currently exist on the utility of screening tools in large samples of adults with SUD in inpatient treatment and the prevalence of ADHD in this population. The aims of this study were to assess the screen positive rate on the Adult ADHD Self Report Scale (ASRS) v.1.1 Screener in a large sample of adults being treated for SUD in a residential treatment facility (RTF) and to establish the imputed prevalence of adult ADHD. METHODS: Adults with SUD who were either newly admitted (abstinent for < 1 week) or in treatment in the RTF (abstinent < 3 months) were administered the ASRS v.1.1 Screener. Adults who screened positive on the ASRS v1.1 Screener (>or= 4/6 significant items) were then administered the Adult Clinician Diagnostic Scale (ACDS) v.1.2 to establish a diagnosis of ADHD and the positive predictive value (PPV) in this population. The imputed prevalence of adult ADHD was calculated based on the known rate of ADHD in the screened positive cohort and a calculated rate of ADHD in the screened negative sample based on prior studies of the ASRS v1.1 Screener in community-based and managed care samples. RESULTS: 1064 adults were screened via the ASRS v.1.1 Screener, with 92 screening positive (8.6% had >or= 4 significant items present). Fifty-three of those who screened positive were diagnosed as having adult ADHD (PPV = 57.6%). The imputed prevalence of adult ADHD in this population was 7.5%. CONCLUSIONS: The PPV for the ASRS v1.1 Screener for adult ADHD in this sample of adults with SUD was similar to that observed in a prior study of a managed care sample, but was somewhat less than that observed in the community-based sample. The imputed prevalence rate for comorbid ADHD in this study of adults with SUD in a RTF was similar to, but slightly lower than the prevalence rate of ADHD in patients with any SUD observed in the community-based sample
— id: 104357, year: 2009, vol: 121, page: 7, stat: Journal Article,

Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder
Adler, Lenard A; Liebowitz, Michael; Kronenberger, William; Qiao, Meihua; Rubin, Richard; Hollandbeck, Millie; Deldar, Ahmed; Schuh, Kory; Durell, Todd
2009 ;26(3):212-221, Depression & anxiety
BACKGROUND: To evaluate the effect of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) and comorbid social anxiety disorder in adults. METHODS: Randomized, double-blind, placebo-controlled, conducted in adults with ADHD and social anxiety disorder. Patients received 40-100 mg ATX (n=224) or placebo (n=218) for 14 weeks following a 2-week placebo lead-in period. Efficacy measures included the Conners' Adult ADHD Rating Scale: Investigator-Rated: Screening Version (CAARS:Inv:SV), Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression-Overall-Severity (CGI-O-S), State-Trait Anxiety Inventory (STAI), Social Adjustment Scale-Self Report (SAS), and Adult ADHD Quality of Life Scale-29 (AAQoL). Safety and tolerability were also assessed. RESULTS: ATX mean change (-8.7+/-10.0) from baseline (29.6+/-10.4) on CAARS:Inv:SV Total ADHD Symptoms score was significantly greater than placebo mean change (-5.6+/-10.2) from baseline (31.2+/-9.4; P<.001). ATX mean change (-22.9+/-25.3) from baseline (85.3+/-23.6) on LSAS Total score was significant compared to placebo mean change (-14.4+/-20.3) from baseline (82.1+/-21.3; P<.001). The visit-wise analysis revealed greater improvement on the CAARS:Inv:SV Total ADHD Symptoms score and LSAS Total score for ATX at every time point throughout the study (P values </=.012). Mean changes in CGI-O-S, STAI-Trait Anxiety scores, and AAQoL Total score were significantly greater for ATX compared to placebo. Mean change for both groups on STAI-State Anxiety scores was comparable. Improvement on SAS for ATX compared to placebo was not significant. Rates of insomnia, nausea, dry mouth, and dizziness were higher with ATX than with placebo. Discontinuation rates due to treatment-emergent adverse events were similar between groups. CONCLUSIONS: ATX monotherapy effectively improved symptoms of ADHD and comorbid social anxiety disorder in adults and was well tolerated
— id: 93887, year: 2009, vol: 26, page: 212, stat: Journal Article,

Once-daily atomoxetine for adult attention-deficit/hyperactivity disorder: a 6-month, double-blind trial
Adler, Lenard A; Spencer, Thomas; Brown, Thomas E; Holdnack, James; Saylor, Keith; Schuh, Kory; Trzepacz, Paula T; Williams, David W; Kelsey, Douglas
2009 Feb;29(1):44-50, Journal of clinical psychopharmacology
This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials
— id: 93888, year: 2009, vol: 29, page: 44, stat: Journal Article,

Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD
Adler, Lenard A; Spencer, Thomas; McGough, James J; Jiang, Hai; Muniz, Rafael
2009 Mar;12(5):449-459, Journal of attention disorders
Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale. Results: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. Conclusion: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD. (J. of Att. Dis. 2009; 12(5) 449-459)
— id: 93886, year: 2009, vol: 12, page: 449, stat: Journal Article,

Short-term effects of lisdexamfetamine dimesylate on cardiovascular parameters in a 4-week clinical trial in adults with attention-deficit/hyperactivity disorder
Adler, Lenard A; Weisler, Richard H; Goodman, David W; Hamdani, Mohamed; Niebler, Gwendolyn E
2009 Dec;70(12):1652-1661, Journal of clinical psychiatry
OBJECTIVE: To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. RESULTS: There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity. CONCLUSIONS: Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880
— id: 107646, year: 2009, vol: 70, page: 1652, stat: Journal Article,

Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study
Adler, Lenard A; Zimmerman, Brenda; Starr, H Lynn; Silber, Steve; Palumbo, Joseph; Orman, Camille; Spencer, Thomas
2009 Jun;29(3):239-247, Journal of clinical psychopharmacology
OBJECTIVE: To assess the efficacy and safety of OROS methylphenidate (Concerta; McNeil Pediatrics Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, Titusville, NJ) in the management of attention-deficit/hyperactivity disorder (ADHD) in adults. METHODS: A randomized, 7-week, double-blind, placebo-controlled, dose-escalation, parallel-group study of OROS methylphenidate 36, 54, 72, 90, or 108 mg/d versus placebo was conducted in adults with ADHD. The primary end point was the Adult ADHD Investigator Symptom Report Scale. Other assessments included the Clinical Global Impressions-Improvement scale, a post hoc responder analysis, adverse events, and vital signs. RESULTS: Two hundred twenty-six subjects (56.2% male; mean age, 39.0 years; range, 18-65 years) were included in the intention-to-treat population (110 subjects on OROS methylphenidate; 116 subjects on placebo). OROS methylphenidate resulted in greater ADHD symptom improvement than placebo as demonstrated by a statistically significantly lower least squares mean change from baseline in Adult ADHD Investigator Symptom Report Scale total score at the final visit (last observation carried forward [LOCF]; P = 0.012). Subjects on OROS methylphenidate also had a significantly lower least squares mean Clinical Global Impressions-Improvement score at the final visit (LOCF; P = 0.008). A significantly greater proportion of subjects on OROS methylphenidate (36.9%, 38/103 subjects) were responders at the final visit (LOCF) compared with placebo (20.9%, 24/115 subjects; P = 0.009). OROS methylphenidate was well tolerated. Adverse events were reported by 93 (84.5%) of the 110 OROS methylphenidate-treated subjects versus 74 (63.8%) of the 116 placebo-treated subjects. No serious treatment-emergent adverse events and no deaths were reported. Similar mean changes from baseline to final visit (LOCF) for systolic and diastolic blood pressures for the OROS methylphenidate and placebo groups were observed. CONCLUSIONS: In a dose escalation ranging from 36 to 108 mg/d, OROS methylphenidate is effective and well tolerated in the management of ADHD in adults
— id: 98906, year: 2009, vol: 29, page: 239, stat: Journal Article,

Issues in the diagnosis and treatment of adults ADHD by primary care physicians
Adler, Lenard; Shaw, David; Sitt, David; Maya, Erica; Morrill, Melinda Ippolito
2009 ;16(5):57-63, Primary Psychiatry
Introduction: The objective of this article is to compare primary care physicians' (POPs') experiences with diagnosing and treating adult attention-deficit/hyperactivity disorder (ADHD) versus other mental health disorders. Methods: Four hundred PCPs who have patients with ADHD, bipolar disorder, depression, generalized anxiety disorder (GAD), or obsessive-compulsive disorder completed a public release survey assessing their experiences and attitudes on diagnosing and treating these disorders. Results: Forty-eight percent of PCPs felt uncomfortable diagnosing adult ADHD and 44% reported that there were no clear diagnostic criteria. Seventy-five percent rated the quality and accuracy of existing adult ADHD diagnostic tools as either poor or fair. Seventy-two percent reported that ADHD is easier to diagnose in children than adults. Sixty-five percent reported deferring to specialists to diagnose adult ADHD, compared to 2% for depression and 3% for GAD. Eighty-five percent reported that they would be more comfortable diagnosing and treating adult ADHD if thorough, straightforward screening tools were validated and if there were effective medications that were neither stimulants nor controlled substances. Discussion: While this survey indicated that adult ADHD is generally accepted by PCPs, the results also indicate that PCPs are significantly less likely to diagnose and treat ADHD in adults without deferring to a specialist, when compared to GAD and depression. The recent development of new screening tools for adult ADHD as well as non-stimulant and novel stimulant medications may reduce PCPs' reliance on specialist referrals. Conclusion: This study highlights a potential need for PCPs for increased education and training in adult ADHD. As the study was conducted 6 years ago, follow-up investigations into the current PCP awareness of adult ADHD are indicated.
— id: 102148, year: 2009, vol: 16, page: 57, stat: Journal Article,

Retrospective safety analysis of atomoxetine in adult ADHD patients with or without comorbid alcohol abuse and dependence
Adler, Lenard; Wilens, Timothy; Zhang, Shuyu; Durell, Todd; Walker, Daniel; Schuh, Leslie; Jin, Ling; Feldman, Peter; Trzepacz, Paula
2009 Sep-Oct;18(5):393-401, American journal on addictions
This post hoc analysis compared the safety of atomoxetine treatment of ADHD in adults with or without comorbid alcohol abuse/dependence. Study completion rates in patients receiving atomoxetine were comparable between heavy drinkers (60.9%) and patients with no alcohol-use disorder (71.0%) but lower in nonheavy drinkers (35.7%); however, there was no significant difference in discontinuation rates due to adverse events or lack of efficacy among these groups. Alcohol-use disorder patients, especially heavy drinkers, generally experienced the greatest frequency of treatment-emergent adverse events in both the atomoxetine and placebo groups. Vital signs and measures of hepatic function were not significantly different among the 3 drinking status groups taking atomoxetine
— id: 104934, year: 2009, vol: 18, page: 393, stat: Journal Article,

Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder
Amsterdam, Jay D; Williams, David; Michelson, David; Adler, Lenard A; Dunner, David L; Nierenberg, Andrew A; Reimherr, Frederick W; Schatzberg, Alan F
2009 ;59(4):227-233, Neuropsychobiology
OBJECTIVE: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. METHOD: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. RESULTS: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. CONCLUSION: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials
— id: 104936, year: 2009, vol: 59, page: 227, stat: Journal Article,

Long-term safety and efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder
Lasser, R; Weisler, R; Young, J; Mattingly, G; Gao, J; Adler, L; Squires, L
2009 SEP ;19(3):S356-S356, European neuropsychopharmacology
— id: 105464, year: 2009, vol: 19, page: S356, stat: Journal Article,

Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder
Weisler, Richard; Young, Joel; Mattingly, Greg; Gao, Joseph; Squires, Liza; Adler, Lenard
2009 Oct;14(10):573-585, CNS spectrums
OBJECTIVE: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score. RESULTS: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P < .0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P < .0001). CONCLUSIONS: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months
— id: 110415, year: 2009, vol: 14, page: 573, stat: Journal Article,

Adult ADHD pharmacotherapy
Adler L.A.
2008 ;10(6):469-, Primary care companion to the Journal of clinical psychiatry
— id: 92149, year: 2008, vol: 10, page: 469, stat: Journal Article,

Best practices in adult ADHD. Neurobiology, pharmacology, and emerging treatment
Adler, Lenard A
2008 Sep;13(9 Suppl 13):4-4, CNS spectrums
— id: 92694, year: 2008, vol: 13, page: 4, stat: Journal Article,

Best practices in adult ADHD: special considerations. Introduction
Adler, Lenard A
2008 Oct;13(10 Suppl 15):4-4, CNS spectrums
— id: 92693, year: 2008, vol: 13, page: 4, stat: Journal Article,

Diagnosing and treating adult ADHD and comorbid conditions
Adler, Lenard A
2008 Nov;69(11):e31-e31, Journal of clinical psychiatry
Many adults with attention-deficit/hyperactivity disorder (ADHD) were never diagnosed as children. The impairment caused by untreated ADHD can complicate, or even lead to, other psychiatric conditions. Accurate diagnosis and efficacious treatment of ADHD in adults, which may include pharmacologic and nonpharmacologic interventions, is vital to improve their functioning. When a patient has ADHD and a co-occurring condition, the clinician should usually treat the most impairing condition first
— id: 93575, year: 2008, vol: 69, page: e31, stat: Journal Article,

Epidemiology, impairments, and differential diagnosis in adult ADHD: introduction
Adler, Lenard A
2008 Aug;13(8 Suppl 12):4-5, CNS spectrums
— id: 92695, year: 2008, vol: 13, page: 4, stat: Journal Article,

Familial transmission of ADHD and psychoactive substance use disorders
Adler, Lenard A
2008 Jan;165(1):11-12, American journal of psychiatry
— id: 93893, year: 2008, vol: 165, page: 11, stat: Journal Article,

The reliability and validity of self- and investigator ratings of ADHD in adults
Adler, Lenard A; Faraone, Stephen V; Spencer, Thomas J; Michelson, David; Reimherr, Frederick W; Glatt, Stephen J; Marchant, Barrie K; Biederman, Joseph
2008 May;11(6):711-719, Journal of attention disorders
OBJECTIVE: Little information is available comparing self- versus investigator ratings of symptoms in adult ADHD. The authors compared the reliability, validity, and utility in a sample of adults with ADHD and also as an index of clinical improvement during treatment of self- and investigator ratings of ADHD symptoms via the Conners Adult ADHD Rating Scale (CAARS). METHOD: We analyzed data from two double-blind, parallel-design studies of 536 adult ADHD patients, randomized to 10-week treatment with atomoxetine or placebo. Outcome variables included ADHD symptom severity (CAARS self- and investigator ratings), psychiatric symptom comorbidity, and functioning. RESULTS: All five CAARS subscales showed good internal consistency at each time point. Similarly, interrater reliability was acceptable for each subscale. Following treatment, CAARS total scores and subscale scores improved significantly from baseline. CAARS subscales also predicted changes in other psychiatric symptoms and functioning. Overall, baseline investigator ratings were stronger predictors of treatment outcome than baseline self-report scores. CONCLUSIONS: The CAARS demonstrated good internal consistency and inter-rater reliability, as well as sensitivity to treatment outcome. The finding of greater predictive power of investigator-rated baseline scores merits further investigation
— id: 80609, year: 2008, vol: 11, page: 711, stat: Journal Article,

Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder
Adler, Lenard A; Goodman, David W; Kollins, Scott H; Weisler, Richard H; Krishnan, Suma; Zhang, Yuxin; Biederman, Joseph
2008 Sep;69(9):1364-73, Journal of clinical psychiatry
OBJECTIVE: To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006. RESULTS: Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia. CONCLUSION: All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients
— id: 93563, year: 2008, vol: 69, page: 1364, stat: Journal Article,

Functional outcomes in the treatment of adults with ADHD
Adler, Lenard A; Spencer, Thomas J; Levine, Louise R; Ramsey, Janet L; Tamura, Roy; Kelsey, Douglas; Ball, Susan G; Allen, Albert J; Biederman, Joseph
2008 May;11(6):720-727, Journal of attention disorders
OBJECTIVE: ADHD is associated with significant functional impairment in adults. The present study examined functional outcomes following 6-month double-blind treatment with either atomoxetine or placebo. METHOD: Patients were 410 adults (58.5% male) with DSM-IV-defined ADHD. They were randomly assigned to receive either atomoxetine 40 mg/day to 80 mg/day (n = 271) or placebo (n = 139). The primary functional outcome measure was the Endicott Work Productivity Scale (EWPS), and the secondary measure was the Adult ADHD Quality of Life (AAQoL). Patients were seen for four visits in 6 months. RESULTS: At 6 months, both groups had nonsignificantly different improvements in EWPS total scores. Atomoxetine-treated patients showed significantly greater improvement than placebo-treated patients on the AAQoL after controlling for baseline severity of ADHD. Both treatment groups had low 6-month study completion rates. CONCLUSION: Following 6-month treatment with atomoxetine, adults with ADHD showed significantly greater improvement in functioning on disease-specific measures of quality of life than patients treated with placebo
— id: 80608, year: 2008, vol: 11, page: 720, stat: Journal Article,

Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study
Adler, Lenard A; Spencer, Thomas J; Williams, David W; Moore, Rodney J; Michelson, David
2008 Nov;12(3):248-253, Journal of attention disorders
OBJECTIVE: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. METHOD: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment. Primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptom score. Adverse events and vital signs were assessed. RESULTS: CAARS-Inv:SV Total ADHD Symptom scores decreased 30.2% (p < .001) during treatment. Similar, significant decreases were noted for the secondary efficacy measures, including the Sheehan Disability Scale Total score, which improved 25.3% (p < .001). Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects. CONCLUSIONS: Results of this open-label study support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD
— id: 93891, year: 2008, vol: 12, page: 248, stat: Journal Article,

Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder
Castellanos, F Xavier; Margulies, Daniel S; Kelly, Clare; Uddin, Lucina Q; Ghaffari, Manely; Kirsch, Andrew; Shaw, David; Shehzad, Zarrar; Di Martino, Adriana; Biswal, Bharat; Sonuga-Barke, Edmund J S; Rotrosen, John; Adler, Lenard A; Milham, Michael P
2008 Feb 1;63(3):332-337, Biological psychiatry
BACKGROUND: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed 'default-mode' network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. METHODS: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. RESULTS: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 x 10(-11), corrected) and portions of posterior cingulate (p < .02, corrected). CONCLUSIONS: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD
— id: 76108, year: 2008, vol: 63, page: 332, stat: Journal Article,

Efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder
Goodman, D; Adler, L; Kollins, SH; Weisler, R; Krishnan, S; Zhang, Y; Biederman, J
2008 JUL ;11(9):292-293, International journal of neuropsychopharmacology
— id: 98131, year: 2008, vol: 11, page: 292, stat: Journal Article,

Cingulate-precuneus interactions: A new locus of dysfunction in attention-deficit/hyperactivity disorder
Milham, MP; Margulies, DS; Kelly, AMC; Uddin, LQ; Di Martino, A; Sonuga-Barke, EJS; Rotrosen, J; Adler, LA; Castellanos, FX
2008 APR 1 ;63(7):43S-43S, Biological psychiatry
— id: 78664, year: 2008, vol: 63, page: 43S, stat: Journal Article,

Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: a retrospective data analysis
Robison, Reid J; Reimherr, Frederick W; Marchant, Barrie K; Faraone, Stephen V; Adler, Lenard A; West, Scott A
2008 Feb;69(2):213-221, Journal of clinical psychiatry
INTRODUCTION: Studies show that, in childhood attention-deficit/hyperactivity disorder (ADHD), boys have the combined type with externalizing behaviors more frequently, and girls have the inattentive type with increased internalizing disorders more frequently. METHOD: This study explored gender differences in adults with ADHD in 2 large, placebo-controlled, multicenter studies conducted from 2000 to 2001. Information collected included 2 measures of ADHD, multiple psychological measures, general physical symptoms, and treatment response. RESULTS: Thirty-four percent of the subjects were female. Women were rated as more impaired on every measure of ADHD symptoms including total Conners' Adult ADHD Rating Scale-Investigator Format (CAARS-INV), total Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), and most subscales of both measures. More women (75%) had combined type compared with men (62%). Women showed a more complex presentation, with higher scores on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression, 17-item version (HAM-D(17)), more sleep problems, and more past DSM-IV Axis I diagnoses. Both sexes displayed substantial impairment on 3 Psychological General Well-Being Schedule factors: tension-anxiety, life satisfaction, and vitality-drive. Women experienced significantly (p = .003) greater rates of emotional dysregulation (37%) versus men (29%) as defined by a cluster of symptoms on the WRAADDS. The emotional dysregulation factor is derived by combining 3 symptoms--temper control, mood lability, and emotional overreactivity--from the Utah Criteria for ADHD in adults. These symptoms are considered associated symptoms in the DSM-IV description of ADHD. Women also experienced greater improvement (p = .011) on this symptom factor. CONCLUSION: In contrast to the results from childhood studies, women were more impaired than men on ADHD scales in our study. The higher level of emotional symptoms and more complicated presentation in women may obscure the diagnosis of ADHD. Thus, the assessments of adults with ADHD should include an exploration of the emotional dimensions of the illness
— id: 93892, year: 2008, vol: 69, page: 213, stat: Journal Article,

Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study
Spencer, Thomas J; Adler, Lenard A; Weisler, Richard H; Youcha, Sharon H
2008 Sep;69(9):1437-48, Journal of clinical psychiatry
INTRODUCTION: The efficacy and safety of triple-bead mixed amphetamine salts (MAS), an oral, once-daily, enhanced extended-release amphetamine formulation designed for a duration of action up to 16 hours, were evaluated in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: In this phase 3, 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD (DSM-IV-TR criteria), subjects (aged 18 to 55 years) were randomly assigned to triple-bead MAS (starting dose 12.5 mg) or placebo. The primary outcome measure was change in ADHD Rating Scale-IV (ADHD-RS-IV). Secondary outcome measures included Clinical Global Impressions (CGI) scale, Time-Sensitive ADHD Symptom Scale (TASS) (measuring extended duration), Brown Attention-Deficit Disorder Scale (BADDS) (measuring executive function), Adult ADHD Impact Module (AIM-A) (measuring quality of life [QOL]), and ADHD-RS-IV hyperactivity-impulsivity and inattentiveness subscales. Adverse events (AEs), vital signs, electrocardiograms (ECGs), and laboratory data were collected. The trial was conducted from January 2005 to June 2005. RESULTS: Triple-bead MAS resulted in significantly greater improvement versus placebo in mean ADHD-RS-IV total score change (p < .0001), CGI-Improvement (p < .0001), TASS total score at 13-16 hours postdose (p = .002), BADDS total score (p < .0001), all AIM-A domains (p < or = .01), and ADHD-RS-IV subscales (p < .01), demonstrating extended duration of efficacy and improvements in executive function and QOL. The most common treatment-emergent AEs included insomnia, dry mouth, decreased appetite and weight, and headache. Most treatment-emergent AEs were mild or moderate in severity. CONCLUSIONS: Triple-bead MAS was significantly more effective than placebo in treating adult ADHD. The extended duration of action up to 16 hours and significant improvements in executive function and QOL address unique treatment needs of adults with ADHD. Treatment-emergent AEs with triple-bead MAS were consistent with amphetamine treatment
— id: 93890, year: 2008, vol: 69, page: 1437, stat: Journal Article,

Attention-deficit/hyperactivity disorder-specific quality of life with triple-bead mixed amphetamine salts (SPD465) in adults: results of a randomized, double-blind, placebo-controlled study
Spencer, Thomas J; Landgraf, Jeanne M; Adler, Lenard A; Weisler, Richard H; Anderson, Colleen S; Youcha, Sharon H
2008 Nov;69(11):1766-75, Journal of clinical psychiatry
OBJECTIVE: To assess the quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) given triple-bead mixed amphetamine salts (MAS), a long-acting amphetamine formulation designed for a duration of action of up to 16 hours. METHOD: 274 adults with ADHD (DSM-IV-TR criteria) were randomly assigned to 7 weeks of double-blind treatment with an optimal dose of triple-bead MAS (12.5 mg to 75 mg) (N = 137) or placebo (N = 137). As a secondary objective of this study, QOL was assessed on the basis of self-reported Adult ADHD Impact Module (AIM-A) scores, describing ADHD-specific QOL in 6 domains and global QOL (questions 1-4). To assess safety, data were collected on adverse events, vital signs, electrocardiograms, laboratory tests, and sleep quality. The trial was conducted from January 2005 to June 2005. RESULTS: Statistically significant improvement between triple-bead MAS and placebo was observed in all 6 ADHD-specific AIM-A subscales. In addition, statistically significant improvement in global QOL between triple-bead MAS and placebo was seen, based on AIM-A question 1 (p = .0006) and question 4 (p = .0001). Patients' age, gender, race, and prior use of stimulant medication were not found to significantly affect AIM-A subscale scores. The most common treatment-emergent adverse events with triple-bead MAS (insomnia, dry mouth, decreased appetite, headache, and weight decreased) were consistent with amphetamine treatment, and their incidence generally decreased with time. CONCLUSIONS: Adults with ADHD showed significantly improved QOL for both ADHD-specific and global measures with triple-bead MAS in comparison to placebo, based on AIM-A scores. Treatment-emergent adverse events were mostly mild to moderate in intensity and were consistent with amphetamine treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00150579
— id: 93889, year: 2008, vol: 69, page: 1766, stat: Journal Article,

Network homogeneity reveals decreased integrity of default-mode network in ADHD
Uddin, Lucina Q; Kelly, A M Clare; Biswal, Bharat B; Margulies, Daniel S; Shehzad, Zarrar; Shaw, David; Ghaffari, Manely; Rotrosen, John; Adler, Lenard A; Castellanos, F Xavier; Milham, Michael P
2008 Mar 30;169(1):249-254, Journal of neuroscience methods
Examination of spontaneous intrinsic brain activity is drawing increasing interest, thus methods for such analyses are rapidly evolving. Here we describe a novel measure, 'network homogeneity', that allows for assessment of cohesiveness within a specified functional network, and apply it to resting-state fMRI data from adult ADHD and control participants. We examined the default mode network, a medial-wall based network characterized by high baseline activity that decreases during attention-demanding cognitive tasks. We found reduced network homogeneity within the default mode network in ADHD subjects compared to age-matched controls, particularly between the precuneus and other default mode network regions. This confirms previously published results using seed-based functional connectivity measures, and provides further evidence that altered precuneus connectivity is involved in the neuropathology of ADHD. Network homogeneity provides a potential alternative method for assessing functional connectivity of specific large-scale networks in clinical populations
— id: 76811, year: 2008, vol: 169, page: 249, stat: Journal Article,

Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature
Wilens, Timothy E; Adler, Lenard A; Adams, Jill; Sgambati, Stephanie; Rotrosen, John; Sawtelle, Robert; Utzinger, Linsey; Fusillo, Steven
2008 Jan;47(1):21-31, Journal of the American Academy of Child & Adolescent Psychiatry
OBJECTIVE: Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals. METHOD: We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search. RESULTS: We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, 'get high,' or to experiment. CONCLUSIONS: The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants
— id: 93597, year: 2008, vol: 47, page: 21, stat: Journal Article,

Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders
Wilens, Timothy E; Adler, Lenard A; Weiss, Margaret D; Michelson, David; Ramsey, Janet L; Moore, Rodney J; Renard, Didier; Brady, Kathleen T; Trzepacz, Paula T; Schuh, Leslie M; Ahrbecker, Lisa M; Levine, Louise R
2008 Jul 1;96(1-2):145-154, Drug & alcohol dependence
OBJECTIVE: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. METHODS: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. RESULTS: Subjects received atomoxetine (n=72) or placebo (n=75) and 80 subjects completed the 12-week double-blind period (n=32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P<.001; placebo: -8.31 [11.44], P<.001, difference: P=.007; effect size=0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P=.93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio=0.74, P=.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. CONCLUSIONS: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior
— id: 79411, year: 2008, vol: 96, page: 145, stat: Journal Article,

A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD
Wilens, Timothy E; Klint, Thorsten; Adler, Lenard; West, Scott; Wesnes, Keith; Graff, Ole; Mikkelsen, Birgit
2008 ;4:24-24, Behavioral & brain functions : BBF
ABSTRACT: BACKGROUND: NS2359 is a potent reuptake blocker of noradrenalin, dopamine, and serotonin. The aim of the study was to investigate the efficacy, safety and cognitive function of NS2359 in adults with a DSM IV diagnosis of ADHD. METHODS: The study was a multi-centre, double-blind, randomized placebo-controlled, parallel group design in outpatient adults (18-55 years) testing 0.5 mg NS2359 vs. placebo for 8 weeks. Multiple assessments including computerized neuropsychological evaluation were performed. RESULTS: There was no significant difference between NS2359 (n = 63) versus placebo (n = 63) on the primary outcome measure reduction in investigator rated ADHD-RS total score (7.8 versus 6.4; p < 0.45). However, in subjects with the inattentive subtype, there were significantly more responders in the NS2359 group compared to placebo (41% versus 7%; p < 0.01). For all secondary variables (ADHD-RS patient rated; The Conners Adult ADHD Scale; The Brown Adult Scale, and CGI-improvement scale) there were no significant differences between the two groups; however, in the inattentive subgroup, the response to treatment was significantly larger than to placebo. NS2359 improved composite factor scores of attention, episodic- and working memory. No serious adverse events were reported with insomnia, headaches and loss of appetite most commonly reported as side effects. CONCLUSION: No overall effect of NS2359 was found on overall symptoms of ADHD. There was also a modest signal of improvement in the inattentive adults with ADHD and cognition warranting further exploration using differing doses
— id: 104937, year: 2008, vol: 4, page: 24, stat: Journal Article,

Functional and psychosocial impairment in adults with undiagnosed ADHD
Able, Stephen L; Johnston, Joseph A; Adler, Lenard A; Swindle, Ralph W
2007 Jan;37(1):97-107, Psychological medicine
BACKGROUND: Identify a group of adults with 'undiagnosed' attention deficit hyperactivity disorder (ADHD) and compare their personal and family medical histories, psychosocial profiles, functional impairment and quality of life with non-ADHD controls. Additionally, compare adults with undiagnosed and diagnosed ADHD to investigate possible reasons why the undiagnosed avoid clinical detection. METHOD: ICD-9 codes for ADHD in administrative claims records and responses to a telephone-administered adult ADHD screener [the Adult ADHD Self-Report Scale (ASRS)] were used to classify approximately 21000 members of two large managed health-care plans as 'undiagnosed' (no coded diagnosis; ASRS positive) or 'non-ADHD' controls (no coded diagnosis; ASRS negative). Patients identified as 'undiagnosed' ADHD were compared with samples of non-ADHD controls and 'diagnosed' ADHD patients (ICD-9 coded ADHD diagnoses) on the basis of demographics, socio-economic status, past and present mental health conditions, and self-reported functional and psychosocial impairment and quality of life. RESULTS: A total of 752 'undiagnosed' ADHD subjects, 199 'non-ADHD' controls and 198 'diagnosed' ADHD subjects completed a telephone interview. Overall, the 'undiagnosed' ADHD cohort demonstrated higher rates of co-morbid illness and greater functional impairment than 'non-ADHD' controls, including significantly higher rates of current depression, and problem drinking, lower educational attainment, and greater emotional and interpersonal difficulties. 'Undiagnosed' ADHD subjects reported a different racial composition and lower educational attainment than 'diagnosed' ADHD subjects. CONCLUSION: Individuals with 'undiagnosed' ADHD manifest significantly greater functional and psychosocial impairment than those screening negative for the disorder, suggesting that ADHD poses a serious burden to adults even when clinically unrecognized
— id: 71286, year: 2007, vol: 37, page: 97, stat: Journal Article,

Managing ADHD in children, adolescents, and adults with comorbid anxiety
Adler, LA; Barkley, RA; Newcorn, JH; Spencer, TJ; Weiss, MD
2007 MAR ;68(3):451-462, Journal of clinical psychiatry
— id: 71469, year: 2007, vol: 68, page: 451, stat: Journal Article,

Introduction
Adler, LA; Newcorn, JH
2007 DEC ;12(12):4-5, CNS spectrums
— id: 75964, year: 2007, vol: 12, page: 4, stat: Journal Article,

From childhood into adulthood: the changing face of ADHD
Adler, Lenard A
2007 Dec;12(12 Suppl 23):6-9, CNS spectrums
— id: 78640, year: 2007, vol: 12, page: 6, stat: Journal Article,

Non-stimulant trials of adult ADHD
Adler, Lenard A
2007 Apr;12(4 Suppl 6):11-13, CNS spectrums
— id: 74171, year: 2007, vol: 12, page: 11, stat: Journal Article,

Non-stimulant trials of adult ADHD
Adler, Lenard A
2007 ;14(4):11-13 Apr, Primary Psychiatry
This discussion will review clinical trials of the nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD) in adults. A variety of other agents have been used to treat ADHD in adults. There have been several reports of tricyclic antidepressants (TCA) use in children and adolescents with ADHD. Several studies have shown efficacy of modafinil, an agent used to improve wakefulness in patients with narcolepsy, to improve ADHD symptoms in children and adolescents. The nicotinic agonists have been investigated. Non-stimulant medications have been shown to have efficacy in adult ADHD. Atomoxetine has been the medication which has the greatest evidence basis of support for efficacy and is also the only FDA approved non-stimulant for the disorder. There are currently no clear practice guidelines established to guide the clinician as to when to use a nonstimulant medication for adults with ADHD.
— id: 97953, year: 2007, vol: 14, page: 11, stat: Journal Article,

The impact, identification, and management of attention-deficit/hyperactivity disorder in adults. Introduction
Adler, Lenard A; Newcorn, Jeffrey H
2007 Dec;12(12 Suppl 23):1-2, CNS spectrums
— id: 78636, year: 2007, vol: 12, page: 1, stat: Journal Article,

Scattered mind : hope and help for adults with attention deficit hyperactivity disorder
Adler, Lenard; Florence, Mari
New York : Penguin, 2007,
— id: 2065, year: 2007, vol: , page: , stat: ,

Diagnosis and treatment of adults with attention-deficit/hyperactivity disorder
Biederman, Joseph; Wilens, Timothy E; Spencer, Thomas J; Adler, Lenard A
2007 ;14(4):1-2 Apr, Primary Psychiatry
Attention-deficit/hyperactivity (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present primary care physicians,psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiological basis, compiles etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric commodities is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds)have shown robust efficacy and tolerability consistent with the treatment responses establishes in children with ADHD, Non-stimulant medication have demonstrated efficacy as well, and may be preferred in patients with tic abd substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adults ADHD. (journal abstract)
— id: 73993, year: 2007, vol: 14, page: 1, stat: Journal Article,

Atomoxetine alleviates executive function impairments in adults with ADHD
Brown, T; Kelsey, D; Holdnack, J; Saylor, K; Adler, L; Spencer, T; Paczkowski, M; Schuh, K; Trzepacz, P
2007 DEC ;17(6):886-886, Journal of child & adolescent psychopharmacology
— id: 75951, year: 2007, vol: 17, page: 886, stat: Journal Article,

Validity of the World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener in a representative sample of health plan members
Kessler, Ronald C; Adler, Lenard A; Gruber, Michael J; Sarawate, Chaitanya A; Spencer, Thomas; Van Brunt, David L
2007 ;16(2):52-65, International journal of methods in psychiatric research
The validity of the six-question World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener was assessed in a sample of subscribers to a large health plan in the US. A convenience subsample of 668 subscribers was administered the ASRS Screener twice to assess test-retest reliability and then a third time in conjunction with a clinical interviewer for DSM-IV adult ADHD. The data were weighted to adjust for discrepancies between the sample and the population on socio-demographics and past medical claims. Internal consistency reliability of the continuous ASRS Screener was in the range 0.63-0.72 and test-retest reliability (Pearson correlations) in the range 0.58-0.77. A four-category version The ASRS Screener had strong concordance with clinician diagnoses, with an area under the receiver operating characteristic curve (AUC) of 0.90. The brevity and ability to discriminate DSM-IV cases from non-cases make the six-question ASRS Screener attractive for use both in community epidemiological surveys and in clinical outreach and case-finding initiatives
— id: 104938, year: 2007, vol: 16, page: 52, stat: Journal Article,

Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study
Michelson, David; Adler, Lenard A; Amsterdam, Jay D; Dunner, David L; Nierenberg, Andrew A; Reimherr, Frederick W; Schatzberg, Alan F; Kelsey, Douglas K; Williams, David W
2007 Apr;68(4):582-587, Journal of clinical psychiatry
OBJECTIVE: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. METHOD: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. RESULTS: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. CONCLUSION: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo
— id: 104939, year: 2007, vol: 68, page: 582, stat: Journal Article,

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder
Spencer, Thomas J; Adler, Lenard A; McGough, James J; Muniz, Rafael; Jiang, Hai; Pestreich, Linda
2007 Jun 15;61(12):1380-1387, Biological psychiatry
BACKGROUND: This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Randomized adults with ADHD (n = 221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement >/=30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p = .006); d-MPH-ER, 30 mg, improved by 13.4 (p = .012); and d-MPH-ER, 40 mg, improved by 16.9 (p < .001). Overall distribution of CGI-I ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children. CONCLUSIONS: Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD
— id: 71294, year: 2007, vol: 61, page: 1380, stat: Journal Article,

Atomoxetine treatment of adults with ADHD and comorbid alcohol abuse
Wilens, TE; Adler, LA; Weiss, MD; Ramsey, JL; Moore, RJ; Renard, D; Levine, LR
2007 DEC ;17(6):887-887, Journal of child & adolescent psychopharmacology
— id: 75952, year: 2007, vol: 17, page: 887, stat: Journal Article,

ADHD: prevalence, diagnosis, and issues of comorbidity
Wilens, TE; Biederman, J; Spencer, TJ; Adler, LA
2007 APR ;12(4):3-+, CNS spectrums
Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHID. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MID, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MID, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MID, reviews stimulant treatment of adult ADHID, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD
— id: 75465, year: 2007, vol: 12, page: 3, stat: Journal Article,

ADHD: for many, it persists into adulthood
Adler L
2006 ;9(11):57-8,62, Clinical Advisor
The good news is that there are tools to pin down a diagnosis and medications that are effective. A psychiatrist provides practical guidance
— id: 70150, year: 2006, vol: 9, page: 57, stat: Journal Article,

Atomoxetine treatment for ADHD: Younger adults compared with older adults
Adler, L; Durell, T; Wilens, T; Paczkowski, M; Schuh, K
2006 JUL ;9(2):S135-S136, International journal of neuropsychopharmacology
— id: 68848, year: 2006, vol: 9, page: S135, stat: Journal Article,

Issues in the treatment and diagnosis of adult attention deficit-hyperactivity disorder (ADHD) by primary care physicians
Adler, L; Morrill, M; Maya, E; Sitt, D; Dostal, P
2006 JUL ;9(2):S254-S254, International journal of neuropsychopharmacology
— id: 68855, year: 2006, vol: 9, page: S254, stat: Journal Article,

Chart review of patients receiving immediate release D-methylphenidate augmentation of sustained release stimulants
Adler, L; Morrill, M; Reingold, L
2006 JUL ;9(2):S254-S254, International journal of neuropsychopharmacology
— id: 68853, year: 2006, vol: 9, page: S254, stat: Journal Article,

Chart review of ADHD patients treated with combination atomoxetine and stimulant therapy
Adler, L; Morrill, M; Shaw, D; Raphael, F
2006 JUL ;9(2):S254-S254, International journal of neuropsychopharmacology
— id: 68854, year: 2006, vol: 9, page: S254, stat: Journal Article,

Do adults and adolescents with ADHD respond differently to atomoxetine?
Adler, L; Wilens, T; Gao, H; Detke, HC; Levine, LR
2006 JUL ;9(2):S134-S134, International journal of neuropsychopharmacology
— id: 68847, year: 2006, vol: 9, page: S134, stat: Journal Article,

Efficacy and safety of once-daily extended-release dexmethylphenidate 30 and 40 mg in adults with AD
Adler, LA; Spencer, T; Wang, J; Pestreich, L; Muniz, R
2006 JUL ;9(2):S229-S229, International journal of neuropsychopharmacology
— id: 68852, year: 2006, vol: 9, page: S229, stat: Journal Article,

Conducting long-term studies: Observations from a functional outcome study for adult attention-deficit/hyperactivity disorder (ADHD)
Adler, LA; Spencer, TJ; Levine, LR; Tamura, R; Ramsey, J; Kelsey, DK; Ball, S; Allen, AJ; Biederman, J
2006 DEC ;16(6):657-657, Journal of child & adolescent psychopharmacology
— id: 70337, year: 2006, vol: 16, page: 657, stat: Journal Article,

Differential diagnosis of attention-deficit/hyperactivity disorder and comorbid conditions
Adler, Lenard A; Barkley, Russell A; Wilens, Timothy E; Ginsberg, David L [Ed]
2006 ;13(5):1-14 May, Primary Psychiatry
Attention-deficit/hyperactivity disorder (ADHD) is a clinical disorder that may be confused with other medical and psychiatric conditions, due to overlapping symptoms. Often, symptoms suggestive of ADHD may be explained by other diagnoses. Medical 'mimics' one should consider when diagnosing a patient with ADHD include sleep deprivation, chronic and acute illness, medication effects, cognitive deficits, and other psychiatric disorders such as Asperger's syndrome, substance use disorders, and mood disorders. ADHD in both children and adults is also associated with academic performance problems, such as learning disabilities and executive functioning deficits. Learning disabilities such as math and spelling deficits are more common in children, although both age groups experience difficulties with reading and listening comprehension. Executive deficits in response inhibition and working memory have been demonstrated to be predictive of impairment in virtually every major life activity. Evaluation of both children and adults with ADHD requires screening for comorbid medical, psychiatric, and learning disorders; executive functioning; and history of school impairment. In this monograph, Russell A. Barkley, PhD, reviews the comorbidity of adult attention-deficit/hyperactivity disorder (ADHD) and learning and executive function disorders. Next, Timothy E. Wilens, MD, discusses differential diagnosis of ADHD as well as the prevalence of psychiatric comorbidity in adult ADHD. Finally, Lenard A. Adler, MD, reviews Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for adult ADHD and reviews the diagnostic and symptom assessment instruments available for the evaluation of ADHD in this population. (journal abstract)
— id: 64594, year: 2006, vol: 13, page: 1, stat: Journal Article,

Combination pharmacotherapy for adult ADHD
Adler, Lenard A; Reingold, Lisa S; Morrill, Melinda S; Wilens, Timothy E
2006 Oct;8(5):409-415, Current psychiatry reports
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders of adulthood. Although clinical guidelines recommend monotherapy with stimulants or atomoxetine, combination pharmacotherapy is a common practice among clinicians. There are four main situations in which combination medications may be necessary: partial response, dose-limiting side effects, associated disorders, and comorbid diagnoses. We present data from two chart reviews that support existing research on combination pharmacotherapy. Adjunct treatment of d-methylphenidate to stimulant medications extended the duration of therapeutic effect. Adjunct treatment of mirtazapine to stimulant medications reduced associated insomnia. These data support previous research that validates the use of combination pharmacotherapy for adults with ADHD
— id: 69589, year: 2006, vol: 8, page: 409, stat: Journal Article,

Validity of pilot Adult ADHD Self- Report Scale (ASRS) to Rate Adult ADHD symptoms
Adler, Lenard A; Spencer, Thomas; Faraone, Stephen V; Kessler, Ronald C; Howes, Mary J; Biederman, Joseph; Secnik, Kristina
2006 Jul-Sep;18(3):145-148, Annals of clinical psychiatry
BACKGROUND: The goal of this study was to validate the pilot Adult ADHD Self-Report Scale (pilot ASRS) versus standard clinician ratings on the ADHD Rating Scale (ADHD RS). METHOD: Sixty adult ADHD patients took the self-administered ADHD RS and then raters administered the standard ADHD RS. Internal consistency of symptom scores was assessed by Cronbach's alpha. Agreement of raters was established by intra-class correlation coefficients (ICCs) between scales. RESULTS: Internal consistency was high for both patient and rater-administered versions (Cronbach's alpha 0.88, 0.89, respectively). The ICC between scales for total scores was also high (0.84); ICCs for subset symptom scores were also high (both 0.83). There was acceptable agreement for individual items (% agreement: 43%-72%) and significant kappa coefficients for all items (p < 0.001). CONCLUSIONS: The pilot Adult ADHD Self-Report Scale symptom checklist is a reliable and valid scale for evaluating ADHD for adults and shows a high internal consistency and high concurrent validity with the rater-administered ADHD RS
— id: 70020, year: 2006, vol: 18, page: 145, stat: Journal Article,

Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine
Adler, Lenard A; Sutton, Virginia K; Moore, Rodney J; Dietrich, Anthony P; Reimherr, Frederick W; Sangal, R Bart; Saylor, Keith E; Secnik, Kristina; Kelsey, Douglas K; Allen, Albert J
2006 Dec;26(6):648-652, Journal of clinical psychopharmacology
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. METHODS: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. RESULTS: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. CONCLUSIONS: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life
— id: 70312, year: 2006, vol: 26, page: 648, stat: Journal Article,

Safety and tolerability of once versus twice daily atomoxetine in adults with ADHD
Adler, Lenard; Dietrich, Anthony; Reimherr, Fred W; Taylor, Leslie V M; Sutton, Virginia K; Bakken, Rosalie; Allen, Albert J; Kelsey, Douglas
2006 Apr-Jun;18(2):107-113, Annals of clinical psychiatry
BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a disorder characterized by hyperactivity, impulsiveness, and inattention that affects 4% of adults. Atomoxetine hydrochloride is an FDA-approved treatment for adult ADHD, but no studies have clarified whether there are advantages to once versus twice daily dosing. METHODS: This randomized, double-blind, multicenter study compared safety and tolerability of 80 mg atomoxetine QD versus 40 mg atomoxetine BID in 218 adults with ADHD. Treatment-emergent adverse events (TEAEs), laboratory values, vital signs, weight, electrocardiograms, scores on the Arizona Sexual Experiences Scale, and efficacy (using the Conners' ADHD Rating Scale-Investigator Rated: Screening Version) were assessed. RESULTS: The overall incidence for any one TEAE was low. There was no significant treatment group difference in likelihood of patients experiencing >/=1 of the four most commonly observed TEAEs (dry mouth, insomnia, nausea, and erectile dysfunction). Frequency of nausea was significantly lower in the 40 mg BID group (16.4%) than the 80 mg QD group (32.4%; p = .007). There were no unexpected safety results. Although both QD and BID treatments were efficacious, the reduction in scores was greater for BID treatment. CONCLUSIONS: Data indicate both dosing strategies are safe, well tolerated, and efficacious in the treatment of adult ADHD. Changes in dosing strategy are unlikely to be accompanied by safety risks, implying that there is room for prescribers to use discretion and to base dosing strategies on individual factors
— id: 66489, year: 2006, vol: 18, page: 107, stat: Journal Article,

Scattered mind : hope and help for adults with attention deficit hyperactivity disorder
Adler, Lenard; Florence, Mari
New York : G.P. Putnam, 2006,
— id: 2064, year: 2006, vol: , page: , stat: ,

The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication
Kessler, Ronald C; Adler, Lenard; Barkley, Russell; Biederman, Joseph; Conners, C Keith; Demler, Olga; Faraone, Stephen V; Greenhill, Laurence L; Howes, Mary J; Secnik, Kristina; Spencer, Thomas; Ustun, T Bedirhan; Walters, Ellen E; Zaslavsky, Alan M
2006 Apr;163(4):716-723, American journal of psychiatry
OBJECTIVE: Despite growing interest in adult attention deficit hyperactivity disorder (ADHD), little is known about its prevalence or correlates. METHOD: A screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD. RESULTS: The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders. CONCLUSIONS: Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD
— id: 66491, year: 2006, vol: 163, page: 716, stat: Journal Article,

Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity
Spencer, Thomas J; Faraone, Stephen V; Michelson, David; Adler, Lenard A; Reimherr, Fred W; Glatt, Stephen J; Biederman, Joseph
2006 Mar;67(3):415-420, Journal of clinical psychiatry
OBJECTIVE: The objective of this study was to determine if measures of broad clinical psychopathology or neuropsychological performance could aid in the prediction of therapeutic response to the highly selective norepinephrine transporter inhibitor, atomoxetine, among adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: We analyzed data from 2 double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomly assigned to 10 weeks of treatment with atomoxetine or placebo and were assessed with Conners' Adult ADHD Rating Scales (CAARS), the General Well-Being Schedule (GWB), the Sheehan Disability Scale, the Stroop Color-Word Test (SCWT), and the Structured Clinical Interview for DSM-IV (SCID) before and after treatment. RESULTS: Therapeutic improvement on atomoxetine as evidenced by reduced CAARS scores was reliably predicted by the presence of a lifetime comorbid diagnosis of depression or post-traumatic stress disorder at baseline, while improvement on subscales of the GWB and Sheehan Disability Scale were predicted by these and other SCID endorsements, such as alcohol and substance use, as well as demographics such as age and gender. In light of the exploratory nature of this work and the many comparisons that were examined in the corresponding regression models, these findings should be regarded as tentative pending replication and extension in another dataset. CONCLUSION: From these findings, we conclude that the variable responsiveness of individuals to atomoxetine cannot be largely accounted for by differences in broad-spectrum psychopathology or neuropsychological indicators of attentional capacity
— id: 66490, year: 2006, vol: 67, page: 415, stat: Journal Article,

ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study
Wilens, Timothy E; Verlinden, Marleen H; Adler, Lenard A; Wozniak, Patricia J; West, Scott A
2006 Jun 1;59(11):1065-1070, Biological psychiatry
BACKGROUND: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conner's Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed. RESULTS: A total of 11 adults with well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was superior to placebo for the CAARS Total Symptom Score, which was the primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD Index and Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was observed; however, the dose-response curve for attention and memory effects as measured by computerized cognitive testing seemed dose-linear. No clinically meaningful findings in safety assessments or side effect profile were observed. CONCLUSIONS: Data from this pilot study suggest that ABT-089 might be effective in treating adult ADHD and that it is well tolerated. On the basis of these promising results, larger, parallel-group ABT-089 studies of longer duration are warranted
— id: 66492, year: 2006, vol: 59, page: 1065, stat: Journal Article,

Acute akathisia
Adler, Lenard A; Angrist, Burt; Rotrosen, John
Drug-induced movement disorders Malden, MA : Blackwell Futura, 2005,
— id: 5275, year: 2005, vol: , page: ?, stat: Chapter,

Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim analysis
Adler, Lenard A; Spencer, Thomas J; Milton, Denai R; Moore, Rodney J; Michelson, David
2005 Mar;66(3):294-299, Journal of clinical psychiatry
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neuropsychiatric disorder that affects 3% to 7% of school-age children and 4% of adults. Its pathophysiology is thought to involve the dopaminergic and nor-adrenergic pathways associated with attention control and impulsivity. These symptoms have largely been defined in the childhood population, but the course of the condition and expression in the adult population are not as well characterized. METHOD: This is an ongoing, 3-year, open-label study consisting of adults with DSM-IV ADHD who were previously enrolled in 1 of 2 double-blind, acute-treatment studies of atomoxetine. The results of the interim analysis reported here were derived from the study of 384 patients at 31 sites who had been studied for a period of up to 97 weeks. The primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) total ADHD symptom score. In addition, safety, adverse events, and vital sign measurements were assessed. RESULTS: Significant improvement was noted with atomoxetine therapy, with mean CAARS-Inv:SV total ADHD symptom scores decreasing 33.2% from 29.2 (baseline of open-label therapy) to 19.5 (endpoint of open-label therapy) (p < .001). Similar and significant decreases were noted for the secondary efficacy measures. Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects, such as increases in heart rate and blood pressure and a slight decrease in weight. CONCLUSION: The results of this interim analysis of an ongoing, open-label study of adults with ADHD support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD
— id: 55955, year: 2005, vol: 66, page: 294, stat: Journal Article,

Training raters to assess adult ADHD: reliability of ratings
Adler, Lenard A; Spencer, Thomas; Faraone, Stephen V; Reimherr, Fred W; Kelsey, Douglas; Michelson, David; Biederman, Joseph
2005 Feb;8(3):121-126, Journal of attention disorders
The standardization of ADHD ratings in adults is important given their differing symptom presentation. The authors investigated the agreement and reliability of rater standardization in a large-scale trial of atomoxetine in adults with ADHD. Training of 91 raters for the investigator-administered ADHD Rating Scale (ADHDRS-IV-Inv) occurred prior to initiation of a large, 31-site atomoxetine trial. Agreement between raters on total scores was established in two ways: (a) by Kappa coefficient (rater agreement for each item with the percentage of raters that had identical item-by-item scores) and (b) intraclass correlation coefficients (reliability). For the ADHDRS-IV-Inv, rater agreement was moderate, and reliability, as measured by Cronbach's alpha, was substantial. The data indicate that clinicians can be trained to reliably evaluate ADHD in adults using the ADHDRS-IV-Inv
— id: 58746, year: 2005, vol: 8, page: 121, stat: Journal Article,

Efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder: a drug-placebo response curve analysis
Faraone, Stephen V; Biederman, Joseph; Spencer, Thomas; Michelson, David; Adler, Lenard; Reimherr, Fred; Glatt, Stephen J
2005 Oct 3;1:16-16, Behavioral & brain functions : BBF
BACKGROUND: The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) among adults by using drug-placebo response curve methods. METHODS: We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. RESULTS: Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. CONCLUSION: From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria
— id: 66493, year: 2005, vol: 1, page: 16, stat: Journal Article,

Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder
Faraone, Stephen V; Biederman, Joseph; Spencer, Thomas; Michelson, David; Adler, Lenard; Reimherr, Fred; Seidman, Larry
2005 Aug;15(4):664-670, Journal of child & adolescent psychopharmacology
OBJECTIVE: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task. RESULTS: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop colorword score. CONCLUSIONS: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD
— id: 66494, year: 2005, vol: 15, page: 664, stat: Journal Article,

Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication
Kessler, Ronald C; Adler, Lenard A; Barkley, Russell; Biederman, Joseph; Conners, C Keith; Faraone, Stephen V; Greenhill, Laurence L; Jaeger, Savina; Secnik, Kristina; Spencer, Thomas; Ustun, T Bedirhan; Zaslavsky, Alan M
2005 Jun 1;57(11):1442-1451, Biological psychiatry
BACKGROUND: Despite growing interest in adult attention-deficit/hyperactivity disorder (ADHD), little is known about predictors of persistence of childhood cases into adulthood. METHODS: A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18-44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS: Blinded clinical interviews classified 36.3% of respondents with retrospectively assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS: No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD
— id: 66497, year: 2005, vol: 57, page: 1442, stat: Journal Article,

The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers
Kessler, Ronald C; Adler, Lenard; Ames, Minnie; Barkley, Russell A; Birnbaum, Howard; Greenberg, Paul; Johnston, Joseph A; Spencer, Thomas; Ustun, T Bedirhan
2005 Jun;47(6):565-572, Journal of occupational & environmental medicine
OBJECTIVE: The prevalence and workplace consequences of adult attention deficit/hyperactivity disorder (ADHD) are unknown. METHODS: An ADHD screen was included in a national household survey (n = 3198, ages 18-44). Clinical re-interviews calibrated the screen to diagnoses of Diagnostic and Statistical Manual of Mental Disorders, 4th edition ADHD. Diagnoses among workers were compared with responses to the WHO Health and Work Performance Questionnaire (HPQ). RESULTS: A total of 4.2% of workers had ADHD. ADHD was associated with 35.0 days of annual lost work performance, with higher associations among blue collar (55.8 days) than professional (12.2 days), technical (19.8 days), or service (32.6 days) workers. These associations represent 120 million days of annual lost work in the U.S. labor force, equivalent to dollar 19.5 billion lost human capital. CONCLUSIONS: ADHD is a common and costly workplace condition. Effectiveness trials are needed to estimate the region of interest of workplace ADHD screening and treatment programs
— id: 66496, year: 2005, vol: 47, page: 565, stat: Journal Article,

The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population
Kessler, Ronald C; Adler, Lenard; Ames, Minnie; Demler, Olga; Faraone, Steve; Hiripi, Eva; Howes, Mary J; Jin, Robert; Secnik, Kristina; Spencer, Thomas; Ustun, T Bedirhan; Walters, Ellen E
2005 Feb;35(2):245-256, Psychological medicine
BACKGROUND: A self-report screening scale of adult attention-deficit/hyperactivity disorder (ADHD), the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS) was developed in conjunction with revision of the WHO Composite International Diagnostic Interview (CIDI). The current report presents data on concordance of the ASRS and of a short-form ASRS screener with blind clinical diagnoses in a community sample. METHOD: The ASRS includes 18 questions about frequency of recent DSM-IV Criterion A symptoms of adult ADHD. The ASRS screener consists of six out of these 18 questions that were selected based on stepwise logistic regression to optimize concordance with the clinical classification. ASRS responses were compared to blind clinical ratings of DSM-IV adult ADHD in a sample of 154 respondents who previously participated in the US National Comorbidity Survey Replication (NCS-R), oversampling those who reported childhood ADHD and adult persistence. RESULTS: Each ASRS symptom measure was significantly related to the comparable clinical symptom rating, but varied substantially in concordance (Cohen's kappa in the range 0.16-0.81). Optimal scoring to predict clinical syndrome classifications was to sum unweighted dichotomous responses across all 18 ASRS questions. However, because of the wide variation in symptom-level concordance, the unweighted six-question ASRS screener outperformed the unweighted 18-question ASRS in sensitivity (68.7% v. 56.3%), specificity (99.5% v. 98.3%), total classification accuracy (97.9% v. 96.2%), and kappa (0.76 v. 0.58). CONCLUSIONS: Clinical calibration in larger samples might show that a weighted version of the 18-question ASRS outperforms the six-question ASRS screener. Until that time, however, the unweighted screener should be preferred to the full ASRS, both in community surveys and in clinical outreach and case-finding initiatives
— id: 66498, year: 2005, vol: 35, page: 245, stat: Journal Article,

Emotional dysregulation in adult ADHD and response to atomoxetine
Reimherr, Frederick W; Marchant, Barrie K; Strong, Robert E; Hedges, Dawson W; Adler, Lenard; Spencer, Thomas J; West, Scott A; Soni, Poonam
2005 Jul 15;58(2):125-131, Biological psychiatry
BACKGROUND: Before 1980, attention-deficit/hyperactivity disorder (ADHD) was called minimal brain dysfunction and included emotional symptoms now listed as 'associated features' in DSM-IV. Data from two multicenter, placebo-controlled studies with 536 patients were reexamined to assess: 1) the pervasiveness of these symptoms in samples of adults with ADHD; 2) the response of these symptoms to atomoxetine; and 3) their association with depressive/anxiety symptoms. METHODS: The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) was used to assess temper, affective lability, and emotional overreactivity, thus identifying patients exhibiting 'emotional dysregulation.' Other DSM-IV Axis I diagnoses were exclusionary. Outcome measures were the Conners' Adult ADHD Rating Scale (CAARS) and the WRAADDS. RESULTS: Thirty-two percent of the sample met post hoc criteria for emotional dysregulation and had higher baseline scores on ADHD measures, a lower response to placebo, and greater response to atomoxetine (p = .048). Symptoms of emotional dysregulation had a treatment effect (p < .001) at least as large as the CAARS (p = .002) and the total WRAADDS (p = .001). Emotional dysregulation was present in the absence of anxiety or depressive diagnosis. CONCLUSIONS: Symptoms of emotional dysregulation were present in many patients with ADHD and showed a treatment response similar to other ADHD symptoms
— id: 66495, year: 2005, vol: 58, page: 125, stat: Journal Article,

Gender differences in adults with ADHD, pretreatment and following treatment with atomoxetine under double-blind conditions
Reimherr, FW; Faraone, SV; Marchant, B; Robison, RJ; Strong, R; Soni, R; Adler, L
2005 OCT ;15(2):S604-S604, European neuropsychopharmacology
— id: 62541, year: 2005, vol: 15, page: S604, stat: Journal Article,

Attention-deficit/hyperactivity disorder in adult patients with posttraumatic stress disorder (PTSD): is ADHD a vulnerability factor?
Adler, L A; Kunz, M; Chua, H C; Rotrosen, J; Resnick, S G
2004 Aug;8(1):11-16, Journal of attention disorders
OBJECTIVE: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/ Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. METHOD: Twenty-five male veterans with PTSD and 22 male veterans with panic disorder were evaluated for ADHD. The data was analyzed using chi-square and student's t-tests. RESULTS: Thirty-six percent of participants with PTSD and 9% of participants with panic disorder met criteria for childhood ADHD. Twenty-eight percent of participants with PTSD and 5% of participants with panic disorder met criteria for current ADHD. CONCLUSIONS: There appears to be a significant association of PTSD with ADHD. ADHD or common predisposing factors may increase the vulnerability for developing PTSD
— id: 48729, year: 2004, vol: 8, page: 11, stat: Journal Article,

Quality-of-life assessment in atomoxetine-treated adult patients with attention-deficit/hyperactivity disorder
Adler, L; Kelsey, DK; Dietrich, A; Reimherr, F; Sangal, RB; Saylor, K; Secnik, K; Sutton, V; Moore, R
2004 OCT ;14(3):S367-S367, European neuropsychopharmacology
— id: 50158, year: 2004, vol: 14, page: S367, stat: Journal Article,

Clinical presentations of adult patients with ADHD
Adler, Lenard A
2004 ;65 Suppl 3(3):8-11, Journal of clinical psychiatry
Attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in an increasingly recognized number of individuals with childhood onset. The symptoms of adult ADHD are similar to the restlessness, distractibility, and impulsivity central to childhood ADHD, but expression of symptoms changes as the individual matures. A childhood history of ADHD is requisite for a diagnosis of adult ADHD, although full DSM-IV criteria for the childhood disorder need not be met as long as significant symptoms and impairment occurred. Three case reports described here illustrate the migration of symptoms and the use of retrospective reporting and rating scales to determine a diagnosis of adult ADHD. These reports also stress the high probability of comorbid disorders and family aggregation of ADHD, as well as the likelihood that the adult with ADHD has developed coping mechanisms to compensate for his or her impairment
— id: 46237, year: 2004, vol: 65 Suppl 3, page: 8, stat: Journal Article,

Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder
Adler, Lenard; Cohen, Julie
2004 Jun;27(2):187-201, Psychiatric clinics of North America
Although some areas of adult ADHD knowledge remain unclear, there isa strong sense of how to proceed with diagnosis using current DSM-IV criteria as a guide. Thorough clinical interview, aided by the use of rating scales for current symptoms and collateral information about childhood from parents or siblings, forms the backbone of the assessment. The poor psychosocial outcomes of patients with ADHD. often a consequence of unrecognized,untreated disorder manifestation, also can serve as a diagnostic indicator. Diagnostic and symptom assessment scales also can be a significant helpin diagnosing and establishing the symptoms of ADHD in adults. It is important to remember that according to DSM-IV, the cardinal criteria for making the diagnosis are the presence of sufficient current symptoms and impairment in two realms (home, school/work, and social interactions). Accordingly, adult ADHD remains a clinical diagnosis, and the clinician-administered interview remains the cornerstone of diagnostic evaluation
— id: 66499, year: 2004, vol: 27, page: 187, stat: Journal Article,

Assessing attention-deficit/hyperactivity disorder in adults: focus on rating scales
Murphy, Kevin R; Adler, Lenard A
2004 ;65 Suppl 3:12-17, Journal of clinical psychiatry
The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults can be a challenging process because it includes making judgments based on clinical interviews, rating scale results, informant ratings, and objective supporting evidence. The patient evaluation should gather information on the severity and frequency of symptoms, the establishment of childhood onset of symptoms, the chronicity and pervasiveness of symptoms, and the impact of symptoms on major life activities. Some of the rating scales being used in the adult population are the Conners' Adult ADHD Rating Scales, the Brown Attention-Deficit Disorder Scale for Adults, the Wender Utah Rating Scale, the ADHD Rating Scale and ADHD Rating Scale-IV, the Current Symptoms Scale, and the recently-developed Adult ADHD Self-Report Scale-v1.1 Symptom Checklist. More research is needed to establish the usefulness of self-administered rating scales compared with investigator-administered scales in the assessment and diagnosis of adult ADHD
— id: 66500, year: 2004, vol: 65 Suppl 3, page: 12, stat: Journal Article,

Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment
Wernicke, Joachim F; Adler, Lenard; Spencer, Thomas; West, Scott A; Allen, Albert J; Heiligenstein, John; Milton, Denai; Ruff, Dustin; Brown, W Jeffrey; Kelsey, Douglas; Michelson, David
2004 Feb;24(1):30-35, Journal of clinical psychopharmacology
Drugs that affect neurotransmitter release can induce changes in neuroregulation during chronic administration. Thus, in addition to recurrence of symptoms of the illness, discontinuation of treatment can be associated with clinical signs and symptoms related to these changes. Atomoxetine, a new drug approved in the United States for treatment of attention deficit/hyperactivity disorder (ADHD), is associated with blockade of the presynaptic norepinephrine transporter. Because treatment of ADHD typically involves chronic treatment, the potential for production of a discontinuation syndrome as well as recurrence of symptoms upon drug discontinuation were assessed as part of the clinical development process. The effects of discontinuation of atomoxetine were assessed in children and adults with ADHD following 9 to 10 weeks of continuous therapy in 4 large studies. Symptoms of ADHD worsened following drug discontinuation but did not return to pretreatment levels. The incidence of discontinuation-emergent adverse events was low and there were no statistically significant differences between the patients abruptly discontinuing from atomoxetine and those continuing on placebo. Discontinuation of atomoxetine did not result in the development of an acute discontinuation syndrome and was well tolerated. It appears that atomoxetine may be discontinued without risk for symptom rebound or discontinuation-emergent adverse effects. Tapering of doses is not necessary when atomoxetine is discontinued
— id: 66501, year: 2004, vol: 24, page: 30, stat: Journal Article,

Efficacy and safety of atomoxetine in adults with Attention Deficit/Hyperactivity Disorder
Dittmann, RW; Adler, L; Michelson, D; Wernicke, J
2003 SEP ;36(5):221-221, Pharamacopsychiatry
— id: 55379, year: 2003, vol: 36, page: 221, stat: Journal Article,

Long-term treatment effects of atomoxetine in adults with attention-deficit/hyperactivity disorder (ADHD)
Michelson, D; Adler, L; Spencer, T; Milton, D; Jones, D
2003 SEP ;13(8):S458-S458, European neuropsychopharmacology
— id: 55429, year: 2003, vol: 13, page: S458, stat: Journal Article,

Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies
Michelson, David; Adler, Lenard; Spencer, Thomas; Reimherr, Frederick W; West, Scott A; Allen, Albert J; Kelsey, Douglas; Wernicke, Joachim; Dietrich, Anthony; Milton, Denai
2003 Jan 15;53(2):112-120, Biological psychiatry
BACKGRAUND: Attention-deficit/hyperactivity disorder (ADHD) has been less studied in adults than in children, and the treatment studies reported to date have been small, single-center trials. To assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, we conducted two large, multicenter treatment trials. METHODS: Two identical studies using randomized, double-blind, placebo-controlled designs and a 10-week treatment period were conducted in adults with DSM-IV-defined ADHD as assessed by clinical history and confirmed by a structured interview (study I, n = 280; study II, n = 256). The primary outcome measure was a comparison of atomoxetine and placebo using repeated measures mixed model analysis of postbaseline values of the Conners' Adult ADHD Rating Scale. RESULTS: In each study, atomoxetine was statistically superior to placebo in reducing both inattentive and hyperactive and impulsive symptoms as assessed by primary and secondary measures. Discontinuations for adverse events among atomoxetine patients were under 10% in both studies. CONCLUSION: Atomoxetine appears to be an efficacious treatment for adult ADHD. Its lack of abuse potential may be an advantage for many patients
— id: 38842, year: 2003, vol: 53, page: 112, stat: Journal Article,

Management of ADHD in adults
Adler, Lenard A; Chua, Hong C
2002 ;63 Suppl 12:29-35, Journal of clinical psychiatry
Although first identified in children in the 19th century, attention-deficit/hyperactivity disorder (ADHD) in adults was not described in the literature until 1976. The symptoms of adult ADHD resemble the symptoms of childhood ADHD, but symptom intensity, especially hyperactivity, may decrease over time. However, due to the challenges and responsibilities of adulthood, a normal day is extremely complicated for the ADHD adult. Molecular genetics and neuroimaging studies confirm that ADHD is a heterogeneous, neurobiological disorder, mainly of dopaminergic and noradrenergic pathways. Trials of pharmacologic treatments in adults with ADHD have produced mixed results due to considerable variability in diagnostic criteria, dosing, and response. This article reviews the history, neurobiology, and pharmacologic management of adult ADHD
— id: 38841, year: 2002, vol: 63 Suppl 12, page: 29, stat: Journal Article,

Treatment predictors of extrapyramidal side effects in patients with tardive dyskinesia: results from Veterans Affairs Cooperative Study 394
Lohr, James B; Caligiuri, Michael P; Edson, Robert; Lavori, Philip; Adler, Lenard A; Rotrosen, John; Hitzemann, Robert
2002 Apr;22(2):196-200, Journal of clinical psychopharmacology
Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD
— id: 66502, year: 2002, vol: 22, page: 196, stat: Journal Article,

Efficacy of mirtazapine in stimulant associated insomnia in patients with ADHD
Adler, LA; Braverman, L; Ginsberg, D
2000 APR 15 ;47(8):159S-159S, Biological psychiatry
— id: 54654, year: 2000, vol: 47, page: 159S, stat: Journal Article,

Akathisia and exacerbation of psychopathology: a preliminary report [In Process Citation]
Duncan EJ; Adler LA; Stephanides M; Sanfilipo M; Angrist B
2000 May-Jun;23(3):169-173, Clinical neuropharmacology
Akathisia has previously been reported to exacerbate psychopathology and to be associated with noncompliance, suicidality, and violence. One previous study found brisk decrements in psychopathology after acute treatment of akathisia with intramuscular biperiden. This study assessed changes in akathisia and psychopathology in 19 patients after separate one-day treatments with intramuscular benztropine and oral propranolol. Benztropine and propranolol led to clinically meaningful and statistically significant decrements in ratings of subjective and objective measures of akathisia and in psychopathology scores. Changes in psychopathology correlated significantly with changes in subjective measures of akathisia after benztropine and with subjective and objective measures of akathisia after propranolol. Changes in akathisia accounted for 9%-42% of the variance in changes in psychopathology. After treatment, statistically significant decrements in Brief Psychiatric Rating Scale (BPRS) positive symptoms were noted, and individual items not directly related to the akathisia syndrome, such as conceptual disorganization, hallucinatory behavior, and unusual thought content declined, although not significantly. These findings, taken together with the results of a similar previous study, indicate that the effect of akathisia in exacerbating psychopathology is large. If suspected, akathisia should be treated promptly
— id: 11597, year: 2000, vol: 23, page: 169, stat: Journal Article,

Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group
Adler, L A; Rotrosen, J; Edson, R; Lavori, P; Lohr, J; Hitzemann, R; Raisch, D; Caligiuri, M; Tracy, K
1999 Sep;56(9):836-841, Archives of general psychiatry
BACKGROUND: Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E. METHODS: The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo. RESULTS: Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales. CONCLUSION: This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia
— id: 132303, year: 1999, vol: 56, page: 836, stat: Journal Article,

Vitamin E in the treatment of
Adler, LA; Edson, R; Rotrosen, J; Lavori, P; Tracy, K; Lohr, J; Hitzemann, R; Caligiuri, M; Raisch, D
1999 APR 15 ;45(8S):108S-108S, Biological psychiatry
— id: 54035, year: 1999, vol: 45, page: 108S, stat: Journal Article,

Long-term treatment effects of vitamin E for tardive dyskinesia
Adler LA; Edson R; Lavori P; Peselow E; Duncan E; Rosenthal M; Rotrosen J
1998 Jun 15;43(12):868-872, Biological psychiatry
BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment. METHODS: To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo. RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo
— id: 23578, year: 1998, vol: 43, page: 868, stat: Journal Article,

Reliability of an instrumental assessment of tardive dyskinesia: results from VA Cooperative Study #394
Caligiuri MP; Lohr JB; Rotrosen J; Adler L; Lavori P; Edson R; Tracy K
1997 Jul;132(1):61-66, Psychopharmacology
Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted by the Department of Veteran Affairs Cooperative Studies Program. One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient. In the present report, we describe the training procedures and results of a multi-center reliability assessment of this procedure. Data from nine study centers comprising 45 individual patients with six trials each (three from left hand and three from right hand) were reanalyzed by an independent investigator and the results were subjected to reliability assessment. For the statistic of interest (average coefficient of variation over trials 2 and 3 for each hand, then take the larger of these two values), we found very high intraclass correlation coefficients for reliability over all patients across sites (ICC = 0.995). We also calculated the reliability of the measures across trials within patient for each combination of hand (right, left, dominant), rater group (site, control), and trials set (all three, trials 2 and 3). For a given hand and trial set, the reliability of the site raters was similar to that of the control. This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training
— id: 23579, year: 1997, vol: 132, page: 61, stat: Journal Article,

Interrater reliability issues in multicenter trials, Part II: Statistical procedures used in Department of Veterans Affairs Cooperative Study #394
Edson R; Lavori P; Tracy K; Adler LA; Rotrosen J
1997 ;33(1):59-67, Psychopharmacology bulletin
The primary goal of Veterans Affairs (VA) Cooperative Study (CS) #394 is to determine if vitamin E is a safe and efficacious treatment for tardive dyskinesia (TD). The study uses various instruments to assess subjects for movement disorders (Abnormal Involuntary Movement Scale [AIMS], and Barnes Akathisia Scale [BAS]), psychopathology (Anchored Brief Psychiatric Rating Scale [BPRS]), and level of functioning (Global Assessment of Functioning scale [GAF]). Since the study involves nine sites, each with its own set of raters, it is important to establish and maintain high interrater reliability (IRR) on these instruments throughout the study and to identify raters who differ significantly from the others. To make this determination, personnel at each site assessed subjects from standardized videotapes on the AIMS, BAS, and Anchored BPRS, and rated written vignettes on the GAF. We fit these data to a two-way additive model to identify nonstandardized raters (i.e., those whose average ratings were significantly lower or higher than the others, or those whose scores, after adjusting for subject and rater effects, were highly variable). The proportion of nonstandardized raters ranged from 7 percent (Anchored BPRS) to 33 percent (AIMS). The estimated intraclass correlation coefficients (ICCs) indicated moderate reliability for the AIMS, BAS, and Anchored BPRS (0.73 to 0.75) and excellent agreement for the GAF (0.90). The companion article (Part I: Tracy et al. 1997, page 53 of this issue) describes the procedures used to train the raters for this study
— id: 23580, year: 1997, vol: 33, page: 59, stat: Journal Article,

Interrater reliability issues in multicenter trials, Part I: Theoretical concepts and operational procedures used in Department of Veterans Affairs Cooperative Study #394
Tracy K; Adler LA; Rotrosen J; Edson R; Lavori P
1997 ;33(1):53-57, Psychopharmacology bulletin
This article describes a standardized method for establishing and maintaining desired levels of interrater reliability (IRR) in multicenter trials. The procedure involves six steps: distribution of procedural guides, distribution of an introduction tape, initial distribution of patient interviews to rate, training at the study kickoff meeting, ongoing IRR monitoring, and group training throughout the study. This method is being used in a national Veterans Affairs Cooperative Study (CS #394), involving nine sites to examine the treatment effects of vitamin E on tardive dyskinesia. The six-step standardized process allowed for early detection of areas of concern in assessment administration. When comparing intraclass correlation coefficients (ICCs) at different points in the initial training, the Barnes Akathisia Scale and Anchored Brief Psychiatric Rating Scale reliability improved from 0.68 to 0.74 and from 0.54 to 0.87, respectively. After analyzing the ratings collected prior to the start of CS #394, data were collected to conduct the first check on Abnormal Involuntary Movement Scale (AIMS) IRR during enrollment; the estimated ICC for the AIMS had decreased from 0.87 to 0.60. Raters were instructed to re-assess the subjects from the first videotape on the AIMS and received additional training. The re-rating indicated very good reliability, 0.84, IRR was measured once for the Global Assessment of Functioning Scale resulting in an ICC of 0.90. The companion article (Part II: Edson et al. 1997, page 59 of this issue) describes the statistical procedures used to measure IRR
— id: 12411, year: 1997, vol: 33, page: 53, stat: Journal Article,

An open label trial of venlafaxine in adults with attention deficit disorder
Adler, LA; Resnick, S; Kunz, M; Devinsky, O
1996 APR 1 ;39(7):421-421, Biological psychiatry
— id: 52982, year: 1996, vol: 39, page: 421, stat: Journal Article,

Co-morbidity of attention deficit disorder in adult patients screened for
Adler, LA; Resnick, S; Rotrosen, J
1996 APR 1 ;39(7):185-185, Biological psychiatry
— id: 52981, year: 1996, vol: 39, page: 185, stat: Journal Article,

Prescribing characteristics of newer generation antidepressants in a veterans affairs psychiatry clinic
Adler, LA; Vanderburg, D; Resnick, S; Rotrosen, J
1996 NOV ;32(3):406-406, Psychopharmacology bulletin
— id: 52725, year: 1996, vol: 32, page: 406, stat: Journal Article,

Nefazodone and akathisia
Eberstein, S; Adler, L A; Angrist, B
1996 Oct 15;40(8):798-799, Biological psychiatry
— id: 106685, year: 1996, vol: 40, page: 798, stat: Journal Article,

Interrater reliability issues in multicenter trials .2. Statistical procedures used in VA Cooperative Study #394
Edson, R; Lavori, P; Tracy, K; Adler, LA; Rotrosen, J
1996 NOV ;32(3):436-436, Psychopharmacology bulletin
— id: 52729, year: 1996, vol: 32, page: 436, stat: Journal Article,

Antioxidant treatment of tardive dyskinesia
Rotrosen J; Adler L; Lohr J; Edson R; Lavori P
1996 Aug;55(1-2):77-81, Prostaglandins, leukotrienes, & essential fatty acids
Tardive dyskinesia (TD) is a frequently occurring side effect of treatment with neuroleptic antipsychotic drugs. TD is a persistent and often irreversible syndrome characterized by abnormal movements, including lingual and orofacial dyskinesia, grimacing, tics, choreic movements of the limbs and trunk, and athetosis and dystonia. In some patients the muscles of respiration and speech may also be involved. There is no established treatment for TD
— id: 23581, year: 1996, vol: 55, page: 77, stat: Journal Article,

Interrater reliability issues in multicenter trials .1. Theoretical concepts and operational procedures in VA Cooperative Study #394
Tracy, K; Adler, LA; Rotrosen, J; Edson, R; Lavori, P
1996 NOV ;32(3):526-526, Psychopharmacology bulletin
— id: 52731, year: 1996, vol: 32, page: 526, stat: Journal Article,

Open-label trial of venlafaxine in adults with attention deficit disorder
Adler LA; Resnick S; Kunz M; Devinsky O
1995 ;31(4):785-788, Psychopharmacology bulletin
Antidepressants or stimulants are commonly used to treat attention deficit disorder (ADD). We report the results of an open-label trial of the recently marketed antidepressant venlafaxine in 16 adult patients with ADD. Patients were treated with venlafaxine (25 to 225 mg/day) for 8 weeks. Four patients discontinued treatment within the first week because of sedation, agitation, or nausea. In the remaining 12 patients, venlafaxine treatment decreased ADD ratings by almost half
— id: 12816, year: 1995, vol: 31, page: 785, stat: Journal Article,

Paroxetine and akathisia
Adler, L A; Angrist, B M
1995 Mar 1;37(5):336-337, Biological psychiatry
— id: 106687, year: 1995, vol: 37, page: 336, stat: Journal Article,

THE IMPORTANCE OF SIDE-EFFECTS IN THE DEVELOPMENT OF NEW ANTIPSYCHOTIC-DRUGS
ROTROSEN, J; ADLER, L
1995 MAY ;25(5):306-310, Psychiatric annals
— id: 87295, year: 1995, vol: 25, page: 306, stat: Journal Article,

TRAINING RATERS TO ASSESS NEUROLEPTIC-INDUCED AKATHISIA USING STANDARDIZED VIDEOTAPES
ADLER, LA; NIERENBERA, AA; FAVA, M; HANNIBAL, J; ROTROSEN, J
1994 MAY 1 ;35(9):696-696, Biological psychiatry
— id: 52474, year: 1994, vol: 35, page: 696, stat: Journal Article,

VITAMIN-E TREATMENT OF TD - DEVELOPMENT OF A VA COOPERATIVE STUDY
ADLER, LA; ROTROSEN, J; LAVORI, P; EDSON, R
1994 MAY 1 ;35(9):730-731, Biological psychiatry
— id: 52478, year: 1994, vol: 35, page: 730, stat: Journal Article,

Vitamin E in tardive dyskinesia: Effects of longer term treatment
Adler, Lenard A.; Peselow, Eric D.; Angrist, Burt; Rosenthal, Michele; Rotrosen, John
1994 ;30(1):87-87, Psychopharmacology bulletin
— id: 106729, year: 1994, vol: 30, page: 87, stat: Journal Article,

Trazodone for antidepressant-associated insomnia
Nierenberg, A A; Adler, L A; Peselow, E; Zornberg, G; Rosenthal, M
1994 Jul;151(7):1069-1072, American journal of psychiatry
OBJECTIVE: The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. METHOD: Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. RESULTS: Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. CONCLUSIONS: Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia
— id: 106119, year: 1994, vol: 151, page: 1069, stat: Journal Article,

Vitamin E treatment of tardive dyskinesia
Adler LA; Peselow E; Rotrosen J; Duncan E; Lee M; Rosenthal M; Angrist B
1993 Sep;150(9):1405-1407, American journal of psychiatry
OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia
— id: 8277, year: 1993, vol: 150, page: 1405, stat: Journal Article,

Vitamin E in tardive dyskinesia: time course of effect after placebo substitution
Adler, L A; Peselow, E; Duncan, E; Rosenthal, M; Angrist, B
1993 ;29(3):371-374, Psychopharmacology bulletin
Alpha-tocopherol (vitamin E) has been found to be effective in the treatment of tardive dyskinesia (TD). Studies to date have been short in duration and have not found long-term carryover effects of vitamin E. The present study examined the persistence of the effects of vitamin E after longer term (36-week) treatment was discontinued. Vitamin E significantly improved TD over this period. However, the effects of vitamin E persisted so that TD scores approached baseline only after 12 weeks of placebo substitution
— id: 106121, year: 1993, vol: 29, page: 371, stat: Journal Article,

A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis
Adler, L A; Peselow, E; Rosenthal, M; Angrist, B
1993 ;29(2):283-286, Psychopharmacology bulletin
A group of 28 patients was treated to compare the effects on akathisia of the following: propranolol (80 mg/day), benztropine (6 mg/day), or placebo. Both propranolol and benztropine significantly improved akathisia by Day 3-5 of treatment. Placebo had no significant effects of akathisia. Three patients developed confusion or forgetfulness by Day 3 of benztropine treatment; these effects cleared upon discontinuation of benztropine
— id: 106120, year: 1993, vol: 29, page: 283, stat: Journal Article,

Assessing negative symptoms and extrapyramidal symptoms in schizophrenia: workshop report
Kane JM; Dauphinais D; Barnes TR; Adler LA; Rifkin A
1993 ;29(1):45-49, Psychopharmacology bulletin
— id: 65783, year: 1993, vol: 29, page: 45, stat: Journal Article,

Acute neuroleptic-induced akathisia
Adler, Lenard A; Angrist, Burt; Rotrosen, John
Drug-induced movement disorders Mt. Kisco NY : Futura, 1992,
— id: 5274, year: 1992, vol: , page: ?, stat: Chapter,

Lack of efficacy of d-propranolol in neuroleptic-induced akathisia
Adler LA; Angrist B; Fritz P; Rotrosen J; Mallya G; Lipinski JF Jr
1991 Feb;4(2):109-115, Neuropsychopharmacology
d-Propranolol lacks clinically significant beta-adrenergic receptor blocking properties, but has the same membrane stabilizing effects as racemic (d,l) propranolol. To assess the role of beta-blockade versus membrane stabilization or other shared nonspecific effects in the therapeutic action of propranolol in neuroleptic-induced akathisia (NIA) we treated 11 patients with NIA in a crossover, double-blind study of d-propranolol versus placebo. Akathisia scores were unchanged after both d-propranolol and placebo. Eight patients were subsequently treated in a nonblind manner with racemic propranolol, with a significant reduction in akathisia scores. These findings suggest that beta-blockade, not membrane stabilization or other shared nonspecific effects, contributes to the efficacy of propranolol in NIA
— id: 23587, year: 1991, vol: 4, page: 109, stat: Journal Article,

Efficacy of betaxolol in neuroleptic-induced akathisia
Adler LA; Angrist B; Rotrosen J
1991 Nov;39(2):193-198, Psychiatry research
Betaxolol, a beta 1-selective antagonist, produced marked improvement in eight patients with neuroleptic-induced akathisia. No further improvement was seen with subsequent propranolol treatment. These findings, along with the results of prior studies of betaxolol and metoprolol, suggest that blockade of central beta 1-receptors may be sufficient for efficacy in akathisia
— id: 23586, year: 1991, vol: 39, page: 193, stat: Journal Article,

Studies on the time course and efficacy of beta-blockers in neuroleptic-induced akathisia and the akathisia of idiopathic Parkinson's disease
Adler LA; Angrist B; Weinreb H; Rotrosen J
1991 ;27(2):107-111, Psychopharmacology bulletin
This investigation reports pilot data on two points originally raised in the earliest reports of the efficacy of beta-blockers in akathisia: their potential utility in the akathisia of idiopathic Parkinson's disease and the possibility of determining a central vs. a peripheral site of action by comparing the time course of the effects of lipophilic and hydrophilic agents. Akathisia improved in 4 patients with idiopathic Parkinson's disease after low dose propranolol treatment. Six patients with neuroleptic-induced akathisia were treated with the hydrophilic beta-blocker nadolol. Effects on akathisia occurred, but evolved much more slowly than after treatment with lipophilic agents, such as propranolol and metoprolol, thus suggesting a central site of action
— id: 23589, year: 1991, vol: 27, page: 107, stat: Journal Article,

Metoprolol versus propranolol
Adler LA; Angrist B; Rotrosen J
1990 Mar 15;27(6):673-675, Biological psychiatry
— id: 23592, year: 1990, vol: 27, page: 673, stat: Journal Article,

Effects of buspirone in seven schizophrenic subjects
Brody D; Adler LA; Kim T; Angrist B; Rotrosen J
1990 Feb;10(1):68-69, Journal of clinical psychopharmacology
— id: 23593, year: 1990, vol: 10, page: 68, stat: Journal Article,

Nifedipine in the treatment of tardive dyskinesia
Duncan E; Adler L; Angrist B; Rotrosen J
1990 Dec;10(6):414-416, Journal of clinical psychopharmacology
There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists
— id: 8225, year: 1990, vol: 10, page: 414, stat: Journal Article,

Basal ganglia calcification in schizophrenia
Fernandez-Bouzas A; Angrist B; Hemdal P; Adler LA; Rotrosen J
1990 Mar 15;27(6):682-685, Biological psychiatry
— id: 23591, year: 1990, vol: 27, page: 682, stat: Journal Article,

Effects of a specific beta 2-receptor blocker in neuroleptic-induced akathisia
Adler L; Duncan E; Angrist B; Hemdal P; Rotrosen J; Slotnick V
1989 Jan;27(1):1-4, Psychiatry research
To assess the role of blockade of beta-receptor subpopulations in the treatment of neuroleptic-induced akathisia (NIA), the specific beta 2-antagonist ICI 118,551 was compared to placebo in a double-blind study. After a baseline evaluation on placebo, patients were treated with ICI 118,551 or placebo. Five of six patients treated with ICI 118,551 showed improvements in NIA, while only one of four patients improved on placebo. Patients were then treated openly with propranolol, a mixed beta 1, beta 2-antagonist. Compared to ICI 118,551, no further improvement on objective measures of akathisia was seen on propranolol. Mean subjective assessments of NIA declined on propranolol, but changes were variable and not statistically significant
— id: 23601, year: 1989, vol: 27, page: 1, stat: Journal Article,

Neuroleptic-induced akathisia: a review
Adler LA; Angrist B; Reiter S; Rotrosen J
1989 ;97(1):1-11, Psychopharmacology
Neuroleptic-induced akathisia (NIA) is a relatively common side effect of neuroleptics, in which patients complain of a subjective sense of restlessness usually referable to the legs and have characteristic motor movements. This paper will review: 1) history of spontaneously occurring syndromes of pathologic restlessness and NIA, 2) the clinical significance of NIA, 3) issues concerning the diagnosis and quantification of NIA, 4) treatments of NIA and 5) possible future directions for research in this area. Special attention will be paid to newer treatments for this syndrome, specifically beta-blockers
— id: 23600, year: 1989, vol: 97, page: 1, stat: Journal Article,

Akathisia: selective beta-blockers and rating instruments
Adler LA; Duncan E; Kim A; Hemdal P; Rotrosen J; Angrist B
1989 ;25(3):451-456, Psychopharmacology bulletin
beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta-2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied
— id: 23599, year: 1989, vol: 25, page: 451, stat: Journal Article,

Treatment of extrapyramidal side-effects
Adler LA; Duncan E; Reiter S; Rotrosen J; Angrist B
1989 Aug;155(11):269-269, British journal of psychiatry
— id: 23594, year: 1989, vol: 155, page: 269, stat: Journal Article,

NEUROLEPTIC-INDUCED AKATHISIA - REPLY
Adler, LA; Angrist, B; Reiter, S; Rotrosen, J
1989 Aug 15;99(1):135-135, Psychopharmacology
— id: 31790, year: 1989, vol: 99, page: 135, stat: Journal Article,

Efficacy of low-dose metoprolol in neuroleptic-induced akathisia
Kim A; Adler L; Angrist B; Rotrosen J
1989 Aug;9(4):294-296, Journal of clinical psychopharmacology
Recent studies have shown that the beta-blockers can be effective treatments for neuroleptic-induced akathisia. However, the relative contributions of beta-1 versus beta-2 blockade to the therapeutic effect of beta-blockers remains unclear. We treated nine patients who had neuroleptic-induced akathisia with low doses (25-100 mg/day) of the beta-blocker metoprolol. At these doses metoprolol causes selective blockade of beta-1 receptors. Seven patients improved after metoprolol; no further substantial changes were seen after subsequent treatment with propranolol. This finding suggests that neuroleptic-induced akathisia can be improved by selective beta-1 blockade
— id: 23595, year: 1989, vol: 9, page: 294, stat: Journal Article,

Effects of verapamil on tardive dyskinesia and psychosis in schizophrenic patients
Reiter S; Adler L; Angrist B; Peselow E; Rotrosen J
1989 Jan;50(1):26-27, Journal of clinical psychiatry
Nine hospitalized schizophrenic patients with tardive dyskinesia were treated with the calcium-channel antagonist verapamil under single-blind conditions. The tardive dyskinesia and activation scores decreased, and the anxiety/depression scores increased. The changes were small but statistically significant
— id: 23602, year: 1989, vol: 50, page: 26, stat: Journal Article,

Effects of calcium-channel antagonists on tardive dyskinesia and psychosis
Adler L; Duncan E; Reiter S; Angrist B; Peselow E; Rotrosen J
1988 ;24(3):421-425, Psychopharmacology bulletin
— id: 23606, year: 1988, vol: 24, page: 421, stat: Journal Article,

Neuroleptic-induced akathisia: propranolol versus benztropine
Adler LA; Reiter S; Corwin J; Herndal P; Angrist B; Rotrosen J
1988 Jan 15;23(2):211-213, Biological psychiatry
— id: 23603, year: 1988, vol: 23, page: 211, stat: Journal Article,

CNS EFFECTS OF BETA-BLOCKADE - A COMPARATIVE-STUDY
ADLER, L
1988 SEP ;24(2):232-237, Psychopharmacology bulletin
— id: 41757, year: 1988, vol: 24, page: 232, stat: Journal Article,

CNS EFFECTS OF BETA-BLOCKADE - A COMPARATIVE-STUDY (PSYCHOMETRIC AND COGNITIVE)
ADLER, L; ROTROSEN, JP; HEMDAL, P; CORWIN, J; PESELOW, E; REITANO, JM; REES, RS
1988 FEB 29 ;140(6):52-54, Postgraduate medicine
— id: 41817, year: 1988, vol: 140, page: 52, stat: Journal Article,

Preliminary studies of clonidine in psychotic patients
Angrist B; Smith M; Adler L; Peselow E; Reitano J; Rotrosen J
1988 ;71(2):115-121, Journal of neural transmission
Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study
— id: 23604, year: 1988, vol: 71, page: 115, stat: Journal Article,

Noradrenergic mechanisms in akathisia: treatment with propranolol and clonidine
Adler L; Angrist B; Peselow E; Corwin J; Rotrosen J
1987 ;23(1):21-25, Psychopharmacology bulletin
— id: 23615, year: 1987, vol: 23, page: 21, stat: Journal Article,

Clonidine in neuroleptic-induced akathisia
Adler LA; Angrist B; Peselow E; Reitano J; Rotrosen J
1987 Feb;144(2):235-236, American journal of psychiatry
Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation
— id: 23612, year: 1987, vol: 144, page: 235, stat: Journal Article,

Pindolol and propranolol in neuroleptic-induced akathisia
Adler LA; Reiter S; Angrist B; Rotrosen J
1987 Sep;144(9):1241-1242, American journal of psychiatry
— id: 23607, year: 1987, vol: 144, page: 1241, stat: Journal Article,

Drug-induced stuttering treated with propranolol
Adler, L; Leong, S; Delgado, R
1987 Apr;7(2):115-116, Journal of clinical psychopharmacology
— id: 138099, year: 1987, vol: 7, page: 115, stat: Journal Article,

TIME COURSE OF EFFECTS OF CLONIDINE - REPLY
ADLER, LA; ANGRIST, B; PESELOW, E; REITANO, J; ROTROSEN, J
1987 ;144(11):1519-1519, American journal of psychiatry
— id: 106734, year: 1987, vol: 144, page: 1519, stat: Journal Article,

DIFFERENTIAL-EFFECTS OF PROPRANOLOL AND BENZTROPINE IN PATIENTS WITH NEUROLEPTIC-INDUCED AKATHISIA
Adler, LA; Reiter, S; Corwin, J; Hemdal, P; Angrist, B; Rotrosen, J
1987 Dec 15;23(3):519-521, Psychopharmacology bulletin
— id: 31301, year: 1987, vol: 23, page: 519, stat: Journal Article,

Atenolol and propranolol in neuroleptic-induced akathisia
Reiter S; Adler L; Angrist B; Corwin J; Rotrosen J
1987 Aug;7(4):279-280, Journal of clinical psychopharmacology
— id: 23608, year: 1987, vol: 7, page: 279, stat: Journal Article,

A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia
Adler L; Angrist B; Peselow E; Corwin J; Maslansky R; Rotrosen J
1986 Jul;149(7):42-45, British journal of psychiatry
Twelve patients with neuroleptic-induced akathisia were treated in a randomised, double-blind, cross-over design with propranolol and matching placebo. Propranolol caused significant decrements in both subjective and objective ratings of akathisia, but not in anxiety scores. This confirms prior findings of the efficacy of propranolol in akathisia induced by neuroleptic treatment
— id: 23620, year: 1986, vol: 149, page: 42, stat: Journal Article,

BETA-BLOCKERS AS A TREATMENT FOR NEUROLEPTIC-INDUCED AKATHISIA
ADLER, L; LIPINSKI, J; ANGRIST, B; COHEN, B; PESELOW, E; ROTROSEN, J
1986 ;9(2):428-430, Clinical neuropharmacology
— id: 106735, year: 1986, vol: 9, page: 428, stat: Journal Article,

Efficacy of propranolol in neuroleptic-induced akathesia
Adler L; Angrist B; Peselow E; Corwin J; Rotrosen J
1985 Jun;5(3):164-166, Journal of clinical psychopharmacology
The effects of propranolol, 20 to 30 mg/day, on neuroleptic-induced akathesia were compared with those of lorazepam, 2 mg/day, and periods of no treatment. Raters were blind to treatment condition. As reported in prior open studies, propranolol was found to be dramatically effective in reducing akathesia induced by neuroleptic treatment
— id: 23624, year: 1985, vol: 5, page: 164, stat: Journal Article,

Differential effects of tricyclic antidepressants on mean arterial pressure in a hypertensive patient
Adler L; Angrist B; Lautin A; Rotrosen J
1983 Apr;3(2):122-122, Journal of clinical psychopharmacology
— id: 23639, year: 1983, vol: 3, page: 122, stat: Journal Article,