Comparison of Quality of Life, Productivity, Functioning and Self-Esteem in Adults Diagnosed With ADHD and With Symptomatic ADHD.

Objective: Investigate the association between diagnosis and outcomes in adults with symptoms of ADHD. Method: The Validate Attitudes and Lifestyle Issues in Depression, ADHD and Troubles with Eating (VALIDATE) study collected sociodemographic and clinical characteristics data, and responses from validated questionnaires on health-related quality of life (HRQoL), work productivity, functioning, and self-esteem. ADHD-diagnosed respondents (n = 444) were matched with respondents with symptomatic ADHD (n = 1,055) within the same sex-by-age group using propensity score matching. Effects of ADHD diagnosis on each outcome were adjusted for covariates that remained imbalanced after matching, using generalized mixed models. Results: After matching, symptomatic respondents (n = 867) had worse outcomes than ADHD-diagnosed respondents (n = 436), as measured by the Work Productivity and Activity Impairment: General Health questionnaire and Sheehan Disability Scale (p < .001). ADHD-diagnosed respondents had better mean EuroQol five-dimensional five-level (EQ-5D-5L) scores and Rosenberg Self-Esteem Scale scores than symptomatic respondents (p < .001). Conclusion: ADHD-diagnosed individuals are more likely to experience better functional performance, work-related productivity, HRQoL, and self-esteem than individuals with symptomatic ADHD.

Long-Term Outcomes of ADHD: Academic Achievement and Performance.

Objective: The aim of this study was to synthesize published data regarding long-term effects of ADHD on information learned (measured via achievement tests) and success within the school environment (academic performance). Method: A systematic search identified 176 studies (1980-2012) of long-term (≥2 years) academic outcomes with ADHD. Results: Achievement test outcomes (79%) and academic performance outcomes (75%) were worse in individuals with untreated ADHD compared with non-ADHD controls, also when IQ difference was controlled (72% and 81%, respectively). Improvement in both outcome groups was associated with treatment, more often for achievement test scores (79%) than academic performance (42%), also when IQ was controlled (100% and 57%, respectively). More achievement test and academic performance outcomes improved with multimodal (100% and 67%, respectively) than pharmacological (75% and 33%) or non-pharmacological (75% and 50%) treatment alone. Conclusion: ADHD adversely affects long-term academic outcomes. A greater proportion of achievement test outcomes improved with treatment compared with academic performance. Both improved most consistently with multimodal treatment.

Clinical Characteristics and Treatment Response to Lisdexamfetamine Dimesylate Versus Placebo in Adults With Binge Eating Disorder: Analysis by Gender and Age.

OBJECTIVE: To describe clinical characteristics and lisdexamfetamine dimesylate (LDX) treatment effects, based on gender and age, in adults diagnosed with moderate to severe binge eating disorder (BED). METHODS: Adults diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined BED of moderate to severe severity were randomized to 12 weeks of dose-optimized LDX (50 or 70 mg) or placebo in 2 studies (conducted from November 26, 2012, to September 25, 2013 [study 1] and from November 26, 2012, to September 20, 2013 [study 2]). These post hoc analyses pooled data by gender (men vs women) and age (< 40 vs ≥ 40 years) across studies; reported P values are nominal (descriptive and unadjusted). RESULTS: The pooled safety analysis and full analysis sets included 745 and 724 participants, respectively (men, n = 105 and n = 97; women, n = 640 and n = 627; < 40 years, n = 398 and n = 386; ≥ 40 years, n = 347 and n = 338). Across subgroups, most participants had a body mass index ≥ 30 kg/m² (63.0%-75.5%). The mean baseline number of binge eating days/wk was comparable across gender (4.6-4.7) and age (4.6-4.9), as was Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total score (gender, 20.42-21.70; age, 21.40-21.63). Least squares mean (95% CI) treatment differences nominally favored LDX in all subgroups (all P < .001) for changes from baseline in binge eating days/wk at weeks 11-12 and in Y-BOCS-BE total score at week 12; no interactions by gender or age were reported. Consistent with the overall profile of LDX, across all subgroups LDX was associated with higher frequencies of treatment-emergent adverse events than placebo and with increases in blood pressure and pulse. CONCLUSIONS: Across gender and age, participants exhibited comparable clinical characteristics and responses to dose-optimized LDX compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01718483 and NCT01718509.

A randomized, double-blind, 3-way crossover, analog classroom study of SHP465 mixed amphetamine salts extended-release in adolescents with ADHD.

OBJECTIVES: To evaluate the duration of efficacy, safety, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: This phase 2, randomized, 3-period, 3-treatment crossover study compared SHP465 MAS (25/50 mg) with placebo and MAS IR (12.5 mg) in 13-17-year-old adolescents with ADHD having ADHD Rating Scale, Version IV (ADHD-RS-IV) total scores ≥24. A laboratory classroom served as a controlled environment during 16-hour observations, with efficacy assessed on the last day of each 7-day treatment period. The primary efficacy analysis compared SHP465 MAS with placebo on Permanent Product Measure of Performance (PERMP) total score averaged over the 16-hour postdose period using a mixed linear model. Comparisons were also conducted between MAS IR and placebo (for assay sensitivity) and between SHP465 MAS and MAS IR. PERMP problems attempted and answered correctly and ADHD symptoms based on ADHD-RS-IV; participant self-report; Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale; and Revised Conner's Parent Rating Scale scores were also evaluated. Safety and tolerability assessments included treatment-emergent adverse events and vital signs. RESULTS: The intent-to-treat population included 84 participants. Least squares mean (95% CI) PERMP total score treatment differences significantly favored SHP465 MAS (combined 25/50 mg) over placebo for the average of all postdose assessment time points (41.26 [32.24, 50.29]; P < 0.0001) and each postdose assessment time point (all P < 0.0001). Similar results were observed for MAS IR versus placebo (all postdose assessment time points averaged: nominal P < 0.0001; each postdose assessment time point: all nominal P < 0.004). The safety and tolerability of SHP465 MAS were consistent with previous reports. CONCLUSIONS: SHP465 MAS significantly improved PERMP total scores versus placebo from 2 to 16 hours postdose in adolescents with ADHD. The safety and tolerability profile of SHP465 MAS was consistent with previous reports of SHP465 MAS in individuals with ADHD.

A 12-Month Open-Label Extension Study of the Safety and Tolerability of Lisdexamfetamine Dimesylate for Major Depressive Disorder in Adults.

PURPOSE/BACKGROUND: Psychostimulant augmentation is considered a potential treatment strategy for individuals with major depressive disorder who do not adequately respond to antidepressant monotherapy. The primary objective of this 12-month open-label extension study was to evaluate the safety and tolerability of lisdexamfetamine dimesylate (LDX) as augmentation therapy to an antidepressant in adults with major depressive disorder. METHODS/PROCEDURES: Eligible adults who completed 1 of 3 short-term antecedent LDX augmentation of antidepressant monotherapy studies were treated with dose-optimized LDX (20-70 mg) for up to 52 weeks while continuing on the index antidepressant (escitalopram, sertraline, venlafaxine extended-release, or duloxetine) assigned during the antecedent short-term studies. Safety and tolerability assessments included the occurrence of treatment-emergent adverse events and vital sign changes. FINDINGS/RESULTS: All 3 antecedent studies failed to meet the prespecified primary efficacy endpoint, so this open-label study was terminated early. Headache (15.5% [241/1559]), dry mouth (13.6% [212/1559]), insomnia (13.1% [204/1559]), and decreased appetite (12.1% [189/1559]) were the most frequently reported treatment-emergent adverse events. The greatest mean ± SD increases observed for systolic and diastolic blood pressure and for pulse were 2.6 ± 10.85 and 1.7 ± 7.94 mm Hg and 6.9 ± 10.27 bpm, respectively. Monitoring determined that less than 1% of participants experienced potentially clinically important changes in systolic blood pressure (10 [0.6%]), diastolic blood pressure (8 [0.5%]), or pulse (6 [0.4%]). IMPLICATIONS/CONCLUSIONS: The overall safety and tolerability of long-term LDX augmentation of antidepressant monotherapy was consistent with the profiles of the short-term antecedent studies, with no evidence of new safety signals.

A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design.

OBJECTIVES: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS-placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo. CONCLUSIONS: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.

A register-based case-control study of health care utilization and costs in binge-eating disorder.

OBJECTIVE: Capturing trends in healthcare utilization may help to improve efficiencies in the detection and diagnosis of illness, to plan service delivery, and to forecast future health expenditures. For binge-eating disorder (BED), issues include lengthy delays in detection and diagnosis, missed opportunities for recognition and treatment, and morbidity. The study objective was to compare healthcare utilization and expenditure in people with and without BED. METHODS: A case-control design and nationwide registers were used. All individuals diagnosed with BED at eating disorder clinics in Sweden between 2005 and 2009 were included (N = 319, 97% female, M age = 22 years). Ten controls (N = 3190) were matched to each case on age-, sex-, and location of birth. Inpatient, hospital-based outpatient, and prescription medication utilization and expenditure were analyzed up to eight years before and four years after the index date (i.e., date of diagnosis of the BED case). RESULTS: Cases had significantly higher inpatient, hospital-based outpatient, and prescription medication utilization and expenditure compared with controls many years prior to and after diagnosis of BED. Utilization and expenditure for controls was relatively stable over time, but for cases followed an inverted U-shape and peaked at the index year. Care for somatic conditions normalized after the index year, but care for psychiatric conditions remained significantly higher. CONCLUSION: Individuals with BED had substantially higher healthcare utilization and costs in the years prior to and after diagnosis of BED. Since previous research shows a delay in diagnosis, findings indicate clear opportunities for earlier detection and clinical management. Training of providers in detection, diagnosis, and management may help curtail morbidity. A reduction in healthcare utilization was observed after BED diagnosis. This suggests that earlier diagnosis and treatment could improve long-term health outcomes and reduce the economic burden associated with BED.

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment.

OBJECTIVES: Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults (18-55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92-111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS: The least squares mean (95% CI) treatment difference (SHP465 MAS-placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 [10.95, 27.63]; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4-16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo. CONCLUSIONS: SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants. Clinical trials registry: clinicaltrials.gov (NCT00202605; https://clinicaltrials.gov/ct2/show/NCT00202605 ).

Network analysis of the Quick Inventory of Depressive Symptomatology: Reanalysis of the STAR*D clinical trial.

Network analysis is yet to be used to examine patient-reported symptom severity and change during citalopram treatment for major depressive disorder. We aimed to identify: (I) network systems; (II) central symptoms; and (III) network differences, in patient-reported depression for baseline, endpoint and change scores. STAR*D data during citalopram treatment were reanalyzed to examine depression based on the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR). Network analyses were computed from the QIDS-SR item-level severity scores at baseline and endpoint, and from estimated change scores based on mixed models, adjusted for confounding by dose and baseline severity. Centrality indices for each symptom were computed. Networks were contrasted for connectivity with permutation tests. Network analyses grouped symptoms consistently as: Sleep disturbances, cognitive and physical avolition, Affect and Appetite. Symptom centrality was highest for Energy at baseline, Mood at endpoint, and Mood and Concentration on change scores. Generally, permutation tests showed that the networks all significantly (p<.05) differed. Results demonstrated: (I) a replicable network group of the symptoms of depression that modestly mapped onto well-known mechanisms for depression; (II) symptoms with high centrality that may be future treatment targets (e.g., mood); and (III) that the form of the networks differed across treatment time-points, thereby contributing centrality as a possible mechanism to the initial severity debate. These findings highlight the utility of focusing on symptoms rather than total scores to understand how treatment unfolds, and tentative mechanisms.

Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: The efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported. METHODS: Across study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2. Participants (18-65 y) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20-70mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores ≥18 and <50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAEs). RESULTS: Least squares mean (95% CI) treatment differences (LDX-placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [-1.7, 2.0], P=0.883) or study 2 (-0.5 [-2.3, 1.3], P=0.583). The only TEAE reported by >5% of LDX participants at twice the placebo rate in both studies was dry mouth. LIMITATIONS: Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response. CONCLUSION: Contrary to expectations, LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy.

Evaluating functional outcomes in adolescents with attention-deficit/hyperactivity disorder: development and initial testing of a self-report instrument.

BACKGROUND: Engaging adolescents in decisions about their health may enhance their compliance with treatment and result in better health outcomes. Treatment outcomes in attention-deficit/hyperactivity disorder (ADHD) are rarely evaluated from the adolescents' point of view. There is also concern that adolescents with ADHD may not have insight about the impacts of their disease. This article describes research conducted to understand the experiences of adolescents with ADHD and how the research was used to develop an adolescent self-report instrument. METHODS: This research involved an iterative process to ensure content validity and was conducted in the following stages: concept identification from literature reviews and interviews with teachers and clinicians; concept elicitation interviews with adolescents with ADHD and their caregivers, review of existing instruments; development of a new instrument and cognitive interviews. Experts in instrument development and translation and clinical practitioners in ADHD also participated. RESULTS: A conceptual framework to measure the impact of ADHD on adolescent functioning identified from concept identification research informed concept elicitation interviews with 60 adolescents with ADHD and their primary caregivers. In the interviews, adolescents discussed difficulties with performing activities in various contexts: school, home, leisure activities and social interactions. Caregivers provided additional insights. The instrument review revealed that none of the existing instruments were suitable to collect data on the elicited concepts; therefore, a new instrument was developed. Revisions were made to the format and content of the instrument (a daily diary) based on feedback received from cognitive testing with 15 adolescents. CONCLUSIONS: Our research helped to obtain a comprehensive understanding of the impacts of ADHD on adolescent functioning, to inform the development of a new instrument for measuring outcomes. Adolescents were able to discuss the impact of ADHD on their lives in concept elicitation interviews and report the impacts of ADHD on a self-report instrument. The new instrument developed to reflect the perspective of adolescents with ADHD can be used to supplement outcome assessments in clinic and research settings. Scientific advocacy for the use of such measures can be valuable to measure outcomes meaningful to adolescents with ADHD and the clinical community.

Initial Severity Effects on Residual Symptoms in Response and Remission: A STAR*D Study During and After Failed Citalopram Treatment.

The effects of initial severity on the time to and course of residual symptoms based on response or remission periods, and during and after failed response to citalopram in major depressive disorder are unknown. STAR*D data during and after failed citalopram treatment were reanalyzed to examine the effect of initial severity on the time to and course of residual symptoms using the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR). During and after failed citalopram treatment, Cox regression and Generalized Estimating Equation models were computed to examine mild and moderate residual symptoms during (1) response based on at least a 50% QIDS-SR reduction, as well as (2) remission based on a QIDS-SR score below 6. Generally, initial severity significantly (P < 0.05) increased the time to and course of residual symptoms at the time of response and remission. The course of select mild and moderate residual symptoms was significantly (P < 0.05) more likely to persist in the presence of initial severity during response than remission (eg, energy) across treatment levels. It is concluded that initial severity is a predictor of the time to and course of residual symptoms. The presence of residual symptoms is more likely during response than remission, thereby directing their definition as a treatment target.

ADHD in the College Setting: Current Perceptions and Future Vision.

OBJECTIVE: To assess perceptions concerning ADHD among U.S. college healthcare providers. METHOD: A 37-question survey was conducted from October 4 to December 2, 2010. Participants were contacted via mail or telephone and compensated for participation. RESULTS: Thirty-eight percent of the respondents (physicians, n = 59; nurses, n = 138; directors, n = 101) viewed ADHD as a "problem"/"very much a problem" at their institution. Referrals for evaluation came from students (84%), psychologists/counselors (68%), or the institution (68%). Although 48% of respondents felt "comfortable"/"very comfortable" in their ability to recognize ADHD, 92% referred students for evaluation. Most respondents (>90%) agreed medication use may be warranted; 52% of respondents who treat ADHD or consult with a specialist (from 95% of physicians to 31% of directors) prescribed pharmacotherapy. CONCLUSION: Although college healthcare providers recognize the importance of treating ADHD, their discomfort in diagnosing and treating ADHD represents a barrier to care for college students.

A review of attention-deficit/hyperactivity disorder in women and girls: uncovering this hidden diagnosis.

OBJECTIVE: To describe the clinical presentation of attention-deficit/hyperactivity disorder (ADHD) in women and girls and factors influencing proper diagnosis and treatment. DATA SOURCES: A PubMed search was conducted in April 9, 2012 for English-language publications from the previous 10 years. Search terms included attention deficit hyperactivity disorder, attention deficit/hyperactivity disorder, ADHD, and AD/HD combined with gender, girls, females, women, continuity, discontinuity, gap, treatment, untreated, and lack of treatment. STUDY SELECTION/DATA EXTRACTION: A total of 41 articles were reviewed for relevance. Reference lists from relevant articles were reviewed for additional publications; sources known to the authors were also included. RESULTS: Attitudes about ADHD among individuals with ADHD and knowledgeable informants (families, teachers, colleagues) vary on the basis of the diagnosed individual's gender. The ADHD prevalence rates are higher among boys than girls. A low index of clinical suspicion exists for girls; their presentation is considered "subthreshold" because inattentiveness is more prominent than hyperactivity/impulsivity. Females with ADHD may develop better coping strategies than males to mask their symptoms. Lastly, anxiety and depression, common comorbidities in female patients with ADHD, can lead to missed or misdiagnosis. If not properly diagnosed and treated, girls with ADHD experience the same negative consequences as boys, including poor academic performance and behavioral problems. Unique issues related to hormonal effects on ADHD expression and treatment response are also experienced by women and girls. CONCLUSIONS: Accurate ADHD diagnosis in women and girls requires establishing a symptom history and an understanding of its gender-specific presentation. Coexisting anxiety and depression are prominent in female patients with ADHD; satisfactory academic achievement should not rule out an ADHD diagnosis.

Cognitive effects of pharmacotherapy for major depressive disorder: a systematic review.

OBJECTIVE: Cognitive impairment frequently accompanies major depressive disorder (MDD) and can persist during remission. This review examined pharmacotherapy effects on cognitive function in MDD. DATA SOURCES: PubMed and EMBASE searches were conducted on July 30, 2013, for English language reports of cognitive assessments following pharmacologic monotherapy or augmentation therapy in MDD. STUDY SELECTION: A total of 43 research reports were identified (31 monotherapy [8 placebo-controlled, 11 active-comparator, 12 open-label], 12 augmentation therapy [7 placebo-controlled, 5 open-label]). DATA EXTRACTION: Results reported in each publication were examined for open-label and placebo- or active comparator-controlled studies. RESULTS: Studies varied widely in terms of size (median, 50 participants; interquartile range, 21-143 participants), populations examined, duration (median, 8 weeks; interquartile range, 6-12 weeks), and neurocognitive assessments used. Most individual studies reported some benefit to cognition with pharmacotherapy, but there was no pattern of response in specific domains and only 12% of individually analyzed changes favored active treatment over placebo or untreated healthy controls. Sample weighted mean effect sizes revealed that verbal memory improved with monotherapy, while the largest treatment effect with augmentation therapy was for visual memory. CONCLUSIONS: Pharmacotherapy may have benefit in reducing cognitive impairment in MDD, with augmentation therapy being a potential approach for addressing cognitive deficits that persist after monotherapy has brought about clinical response or remission. However, given the wide variability in study design and treatment duration across studies, these findings should be interpreted cautiously. More definitive research is required before firm conclusions can be reached.

Preclinical pharmacology of amphetamine: implications for the treatment of neuropsychiatric disorders.

The primary mechanism by which amphetamine exerts its neurobehavioral effects is through an enhancement of synaptic monoamine levels, which is mediated by interactions with monoamine transporters, storage, and metabolism. However, preclinical data are now emerging that support more widespread neurobiologic effects for amphetamine. This review describes preclinical evidence suggesting that direct interactions of amphetamine with monoamine systems, which results in increased synaptic monoamine availability, has downstream effects on nonmonoaminergic systems, including glutamate, endogenous opioid, endocannabinoid, and acetylcholine systems. Furthermore, evidence suggests that amphetamine can modulate synaptic plasticity through modulation of glutamatergic systems, intracellular signaling cascades, and neurotrophic factor activity. Functional activity of these systems is implicated in the regulation of neurobehavioral processes that include cognition, mood, motivated behavior/hedonic processes/addiction, and arousal. As such, the ability of amphetamine to influence the function of systems that mediate these processes suggests amphetamine-based agents may have utility in the treatment of psychiatric disorders in which these systems and processes are dysfunctional. Amphetamine-based agents are currently approved by the US Food and Drug Administration only for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. Preclinical and clinical research for amphetamine-based pharmacotherapy for other psychiatric disease states is examined. This should encourage further research on the preclinical pharmacology of amphetamine and its implications for the treatment of neuropsychiatric disorders.

Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder.

Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤ 18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ≥ 60) on stable antidepressant monotherapy for ≥ 8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean ± standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2 ± 8.88; LDX, 76.8 ± 9.66) to week 9/EOS (placebo, 61.4 ± 14.61; LDX, 55.2 ± 16.15); the LS mean (95% CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.

Sociocultural issues in african american and Hispanic minorities seeking care for attention-deficit/hyperactivity disorder.

OBJECTIVE: To review the sociocultural factors that may affect the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD) in African American and Hispanic minorities seen in the primary care setting in the United States. DATA SOURCES: Searches on MEDLINE and PubMed were conducted in April and September 2012 on ADHD and its related problems and disabilities. A general search was conducted using the terms (attention deficit hyperactivity disorder OR attention deficit/hyperactivity disorder OR ADHD OR AD/HD) AND (ethnicity OR cultural OR culture). Issues of particular relevance to racial and ethnic minorities utilizing health care services were researched using the string (black OR African OR Hispanic OR Latino OR minority OR racial) combined with terms relating to access, insurance, comorbidity, high-risk behavior, treatment compliance, and nonpharmacologic modalities. Searches were limited to English-language citations, and no date parameters were used. References identified as pertinent to this review were selected for citation. STUDY SELECTION/DATA EXTRACTION: Information revealing contrasts between minorities and the US non-Hispanic white population was organized in distinct categories, such as access to medical care and insurance, cultural attitudes, and the effects of stigmatization. The authors also provide perspectives for the primary care physician from their own clinical experience. DATA SYNTHESIS: Rates of diagnosis of in the United States are higher for non-Hispanic whites than for minorities, yet true prevalence is probably similar across racial-ethnic groups. When the stigma of mental illness is added to the challenges faced by racial/ethnic minorities or immigrant status, patients may be especially sensitive. Underuse of clinical services may reflect economic limitations on access to care, cultural attitudes toward mental illness, and the effects of real or perceived prejudice and stigmatization. CONCLUSIONS: Primary care clinicians in the United States should seek to become more aware of cultural factors that could interfere with the recognition and management of ADHD.

A physician's guide to helping patients with ADHD find success in the workplace.

The impact of untreated adult attention-deficit/hyperactivity disorder (ADHD) in the workplace can be substantial, and employees with ADHD often confront frustration, employer disappointment, and low performance ratings. As a result, adults with ADHD may seek treatment from primary care providers to improve occupational performance. Previously considered a behavior disorder primarily affecting children and adolescents, ADHD in adulthood presents primarily as a cognitive disorder. Self-management deficits play a greater role in adult ADHD, particularly with respect to occupational and interpersonal functioning. Although specialized resources are available to assist adults with ADHD, many afflicted individuals may be unaware or unable to access them. Primary care providers who may be treating adults with ADHD are in a unique position to help them obtain the care and support needed to build appropriate skills and manage occupational issues. In this review, a literature search of the past 10 years was conducted to identify articles concerning ADHD and its impact on individuals in the workplace. The influence of ADHD on occupational functioning is discussed in the context of self-management impairments, diagnosis and assessment, and management strategies. With early and successful intervention, adults with ADHD may be able to become more aware of the impact of ADHD on work performance and achieve successful occupational experiences.