Barrie K. Marchant

The Reliability and Validity of Self- and Investigator Ratings of ADHD in Adults

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. (J. of Att. Dis. 2008; 11(6) 711-719)

A one year trial of methylphenidate in the treatment of ADHD.

Objective: To determine the effects of long-term methylphenidate treatment on symptom severity and social adjustment in adult ADHD. Method: Adults (n = 116) meeting operational diagnostic criteria for ADHD (the “Utah Criteria”) entered a randomized double-blind crossover trial of methylphenidate and placebo. Participants who improved on immediate-release methylphenidate entered a 12-month, open-label trial. Outcomes were assessed using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), Clinical Global Impression—Improvement (CGI-I), global assessment of functioning (GAF), and the Weissman Social Adjustment Scale (WSAS). Results: In the double-blind trial more patients improved (50% reduction of symptoms) receiving methylphenidate (74%) than placebo (21%, p = .001). During the open-label trial, symptom severity decreased 80% from baseline, and the WSAS decreased >50% in all subscales. The average GAF improved significantly (p < .0001). Conclusion: ADHD adults, who responded to methylphenidate in a short-tem, placebo-controlled trial, responded to long-term treatment with marked improvements in ADHD symptoms and psychosocial functioning.

Borderline personality disorder in patients with bipolar disorder and response to lamotrigine

BACKGROUND Recent reports suggesting lamotrigine as an effective treatment in bipolar disorder, and perhaps borderline personality disorder, a common comorbid personality disorder in bipolar patients, led us to retrospectively examine patients from two bipolar studies to investigate this pattern of comorbidity, and to determine whether lamotrigine effected the dimensions of borderline personality. METHODS Fifteen months following entry into either study, we retrospectively assessed DSM-IV dimensions of borderline personality disorder pre- and post-treatment with lamotrigine in 35 bipolar patients. RESULTS Forty percent met criteria for borderline personality disorder; this subgroup had a more frequent history of substance abuse and childhood symptoms of attention deficit hyperactivity disorder (ADHD). Dimensions of borderline personality improved significantly with treatment in both patient groups, and corresponded with response of bipolar symptoms. Six (43%) comorbid bipolar patients endorsed three or fewer criteria of borderline personality during treatment with lamotrigine. There was a trend for comorbid bipolar patients to require a second psychoactive medication in addition to lamotrigine during extended treatment. LIMITATIONS Criteria for borderline personality and improvement were assessed retrospectively in an open manner. CONCLUSIONS Dimensions of borderline personality disorder may respond to lamotrigine in comorbid bipolar patients; controlled studies appear warranted. Bipolar studies should assess and specify the number of patients with personality disorders in the trial.

Narrow-band blue-light treatment of seasonal affective disorder in adults and the influence of additional nonseasonal symptoms

Background: Bright visible‐spectrum light therapy has proven effective in the treatment of seasonal affective disorder (SAD) and recent basic research suggests that blue wavelengths ∼470 nm account for that effectiveness. To more stringently test the importance of these wavelengths, bright red‐light was used for the placebo (control) condition. Methods: Thirty subjects meeting DSM‐IV criteria for SAD were randomized to narrow‐band light‐emitting diode panels emitting blue‐ or red‐light in this 3‐week, parallel, double‐blind trial. Twenty‐five subjects participated in an open‐label blue‐light follow‐up. Subjects were divided in a blinded, post hoc manner into two groups: SAD only and those experiencing depression with seasonal intensification. The outcome was assessed using Hamilton Depression Rating Scale–17 item version (HAMD‐17) and the Structured Interview Guide for the Hamilton Depression Rating Scale—SAD version. Responders were defined by Clinical Global Impression—Improvement scale. Results: HAMD‐17 scores improved more under the blue‐light condition (51%) than under the red‐light condition (32%) (P=.05). Further, in the blue arm 60% of subjects responded compared with 13% in the red arm (P=.01). During the open‐label phase, subjects from both double‐blind arms improved over baseline. SAD alone patients responded numerically better to treatment than those experiencing depression with seasonal intensification during both treatment periods. Conclusions: Narrow bandwidth blue‐light therapy proved superior to red‐light therapy. Blue‐light therapy produced results similar to both previous 10,000 lux visible‐spectrum light studies and many medication studies. The use of bright red panels supported claims that wavelengths of ∼470 nm account for the documented effectiveness of light therapy. Depression and Anxiety, 2009.

Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms.

Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover trial employed the Wender—Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and Connor’s Adult ADHD Rating Scale (CAARS) and two measures of adult ODD. Treatment responses of all participants and four subgroups (ADHDalone, ADHD + ED, ADHD + ODD, and ADHD + ED + ODD) were assessed. Results: Around 23% of baseline participants were ADHD alone, 31% were ADHD + ED, 10% were ADHD + ODD, and 36% were ADHD + ED + ODD. There was a significant treatment effect for all symptom areas and all four subgroups. MTS was associated with significantly more adverse events, especially dermatologic side effects. Conclusions: MTS was effective in treating adult ADHD. This clinical trial included numerous participants meeting criteria for ED and ODD. All ADHD symptoms responded positively to treatment with MTS.

ADHD IN ADULTS

Attention-deficit/hyperactivity disorder (ADHD) in adults is a common-and, frequently undiagnosed-psychiatric disorder. This article will focus on the symptoms, associated features, diagnosis, differential diagnosis, prevalence, etiology and treatment of this illness.

Genetic polymorphisms in the treatment of depression: Speculations from an augmentation study using atomoxetine

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.

A pooled MADRS/IDS cross-correlation analysis: clinician and patient self-report assessment of improvement in core depressive symptoms with adjunctive aripiprazole.

Background: These analyses aimed to examine the pattern of improvement in depression symptoms with adjunctive aripiprazole. Methods: Data were pooled (724 subjects: n = 356 placebo, n = 368 aripiprazole) from 2 double-blind, 6-week aripiprazole studies. Pearson correlation coefficients (r) were calculated between changes on the Montgomery-Asberg Depression Rating Scale (MADRS) line items and selected Inventory of Depressive Symptomatology (IDS) line items using last observation carried forward. The magnitude of change was expressed as a between-group effect size (ES). Results: At end point, adjunctive aripiprazole demonstrated significant improvement versus antidepressant therapy alone in 8 of the 10 MADRS items (MADRS total score Cohen effect size = 0.37) and 12 of the 30 IDS items (IDS total score Cohen ES = 0.18). Analysis of correlation data identified 5 MADRS items assessing mood, lassitude, inability to feel, self-worth, and suicidal thoughts that correlated with similar IDS items; these showed a similar pattern of rapid, sustained response to adjunctive aripiprazole and a similar ES. Other symptoms associated with depression (tension associated with feeling anxious, irritability, and lack of concentration) did not show statistically significant changes on either scale at end point. The IDS identified an additional 3 important depression-related symptoms (diminished libido, view of self, and interpersonal sensitivity) that showed significant rapid and sustained improvement with adjunctive aripiprazole. Conclusions: This cross-correlation analysis confirmed that improvement in core depressive symptoms with adjunctive aripiprazole was identified by both clinicians and patients. Clinically, these changes were maintained during the study. Theoretically, these findings lead to important questions regarding neurochemical changes produced by aripiprazole when used in combination with antidepressants.

Oppositional Defiant Disorder in Adults With ADHD

Objective: Oppositional defiant disorder (ODD) is the most common comorbid condition in childhood ADHD. This trial was prospectively designed to explore ODD symptoms in ADHD adults. Method: A total of 86 patients in this placebo-controlled, double-blind trial of methylphenidate transdermal system (MTS) were categorized based on the presence of ODD symptoms in childhood and adulthood, and then were compared for baseline and outcome differences. Results: In all, 42% met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ODD as adults and were significantly more impaired on measures of ADHD, personality disorder, and substance abuse and 27% had childhood ODD that had resolved. Childhood and adult ODD symptoms were significantly correlated. ODD and ADHD symptoms improved significantly with MTS (p < .001), and the most consistently significant results were found in participants with adult ODD. Conclusion: A total of 69% met criteria for ODD as children and/or adults. Understanding how ODD interacts with ADHD to impact personality disorder, substance abuse, and treatment response has important clinical, social, and theoretical implications.

The effect of personality disorder symptoms on response to treatment with methylphenidate transdermal system in adults with attention-deficit/hyperactivity disorder.

OBJECTIVE This trial was designed to prospectively explore the relationship among personality disorder (PD) symptoms, attention-deficit/hyperactivity disorder (ADHD), and treatment response in a randomized, double-blind, crossover clinical trial of methylphenidate transdermal system (MTS) and to confirm results of a prior exploratory study. METHOD 67 adults who met the Utah and/or DSM-IV-TR criteria for ADHD were recruited with no attempt to include or exclude patients with PD. Responders were defined by a 50% improvement on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the primary outcome measure. Personality disorder was diagnosed by the clinicians using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders Questionnaire, several self-report scales, and clinical observations. Subjects were categorized as: no PD (PD-negative), 1 PD (PD-positive), and 2 or more PDs (PD-plus). The study was conducted from February 2007 to December 2009 at the Mood Disorders Clinic at the University of Utah School of Medicine, Salt Lake City. RESULTS 37% (n = 25) were PD-positive, and another 27% (n = 18) were PD-plus. In those with a PD, 65% (n = 28) had a cluster C diagnosis, 44% (n = 19) cluster B, and 5% (n = 12) cluster A. PD-plus subjects had significantly higher levels of oppositional defiant disorder (ODD) symptoms (P = .007) and emotional dysregulation (P = .004). 71% (15/21) of the PD-positive and PD-negative subjects were responders in the MTS arm (P < .001) as opposed to 38% (6/16) of the PD-plus subjects (P = .24). Conversely, the interaction between treatment (placebo versus MTS) and the 3 PD groups was not statistically significant (P = .46) when the total WRAADDS was used as the outcome measure. CONCLUSIONS Personality disorder status was associated with more complex ADHD, especially high levels of emotional dysregulation and ODD symptoms. There was a significant treatment effect for PD-positive and PD-negative, but not PD-plus subjects. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00506285.