The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: This is the first controlled pharmacologic study in either adults or children with uncomplicated, treatment-resistant attention-deficit/hyperactivity disorder (ADHD). This study augmented stimulant therapy with the atypical antipsychotic brexpiprazole. The Food and Drug Administration preapproved primary outcome measure (Conners' Adult ADHD Rating Scale [CAARS]) showed no drug-placebo differences. Often studies showing no efficacy on the prestudy, defined primary outcome variable go unpublished. While this is decried, publishing studies with equivocal results remains rare. This reanalysis highlights trends in secondary measures having implications for treatment and research regarding treatment resistant ADHD. METHODS: Initially, 559 stimulant-naive and 174 prior stimulant nonresponders received methylphenidate osmotic-release oral system, dexmethylphenidate hydrochloride, lisdexamfetamine, or mixed amphetamine salts. After 5 weeks, 168 stimulant-naive patients and 68 prior stimulant nonresponders who failed treatment were randomized to brexpiprazole or placebo in a 2:1 ratio while the remaining were on the stimulant. Outcome was measured with the CAARS, Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Clinical Global Impression, and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). The WRAADDS contains 2 factors: attention and emotional dysregulation. RESULTS: Stimulant-naive patients showed no improvement with adjunctive brexpiprazole. Prior stimulant nonresponders displayed no brexpiprazole effect on the CAARS, Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory. In contrast, the WRAADDS detected a trend in treatment benefit, primarily through emotional dysregulation symptoms. Adverse effects on brexpiprazole and placebo were equivalent. CONCLUSIONS: Brexpiprazole might be effective in ADHD adults who are nonresponders to 2 or more stimulants. Future trials in treatment-resistant ADHD should use a 1:1 randomization and use a measure of ADHD symptoms that includes emotional dysregulation.

ADHD and Anxiety: Clinical Significance and Treatment Implications.

In comparison to the DSM formulation of ADHD, we have proposed that ADHD in adults should be divided into Inattentive and Emotional Dysregulation Presentations. Under both systems, there is potential overlap with generalized anxiety disorder (GAD). We compared data from four distinct populations: ADHD clinical trials, GAD clinical trials, an ADHD clinic, and a forensic clinic. Approximately 25% of patients in each population had comorbid ADHD and anxiety. Comorbid subjects reported more childhood ADHD symptoms and higher scores on ADHD scales and were more likely to fit criteria for ADHD Emotional Dysregulation Presentation or DSM-IV combined type. Comorbid subjects did not drop out at a higher rate and showed significant drug-placebo differences on ADHD symptoms, including Emotional Dysregulation. Conversely, although symptoms of anxiety decreased, there was no drug-placebo difference in improvement.

Personality Disorder in Adult Attention-Deficit/Hyperactivity Disorder: Attrition and Change During Long-term Treatment.

Personality disorders (PDs) are commonly found in adults with attention-deficit/hyperactivity disorder (ADHD) and are associated with increased ADHD symptoms and psychosocial impairment. To assess the impact of PDs or personality traits on retention rates in ADHD trials and whether treating ADHD affects the expression of PD, data were analyzed from 2 methylphenidate trials. Assessment of PDs and personality traits included using the Wisconsin Personality Disorders Inventory IV and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Personality Disorders. Attention-deficit/hyperactivity disorder symptoms were evaluated using the Wender-Reimherr Adult Attention Deficit Disorder Scale. Major findings were that subjects with cluster A, cluster B, passive-aggressive, or more than 1 PD showed more attrition. Subjects dropping out also had more schizoid and narcissistic traits. Attention-deficit/hyperactivity disorder symptoms (p < 0.001) and all personality traits (range, p = 0.03 to p = 0.001) improved, but there was almost no correlation between changes on these 2 measures. Conversely, of 11 Wisconsin Personality Disorders Inventory IV items that improved most, 8 resembled ADHD or oppositional defiant disorder symptoms.

Psychometric properties of the Self-Report Wender-Reimherr Adult Attention Deficit Disorder Scale.

BACKGROUND: The Self-Report Wender-Reimherr Adult Attention Deficit Disorder Scale (SR-WRAADDS) assesses the same 7 attention-deficit/ hyperactivity disorder (ADHD) domains as the interviewer-administered WRAADDS. METHODS: A normative sample was recruited, and additional participants came from trials involving ADHD, anxiety, or depression. Using the investigator-administered WRAADDS, participants in the ADHD sample were classified as ADHD inattentive presentation or ADHD emotional dysregulation presentation. RESULTS: In the ADHD sample, the SR-WRAADDS correlated with the investigator-rated version WRAADDS (P < .001). In comparing adults with ADHD with normal controls, all SR-WRAADDS domains demonstrated discriminate validity (P < .001); a cut point was identified yielding sensitivity of 97% and specificity of 89%. In comparison, in screening for ADHD in depression or anxiety disorders, sensitivity was 87% and specificity, 49%. Internal consistency was satisfactory (Cronbach α = 0.78; split-half reliability r = 0.92). Factor analysis yielded a 2-factor solution: one reflected emotional dysregulation; the other, inattention and disorganization. Detecting ADHD emotional dysregulation presentation within the ADHD sample, as the "disorder-of-interest," SR-WRAADDS and the investigator-rated WRAADDS agreement was 72% (sensitivity, 87%; specificity, 49%). The SR-WRAADDS detected a methylphenidate vs placebo treatment effect (P < .001). CONCLUSIONS: The psychometric properties of the SR-WRAADDS support its use in research and clinical practice. Emotional domains are integral to its assessment of adult ADHD.

Psychometric data and versions of the Wender Utah Rating Scale including the WURS-25 & WURS-45.

Our associated paper presented a psychometric evaluation of the Wender Utah Rating Scale (WURS) and its abbreviated version, the WURS-25. Instead of actual factors scores, we employed "item averages" calculated by the average score of each item comprising that factor. We did not present a factor analysis of the WURS-25. Herein we identify items of the full WURS that are redundant or not part of any of the scale's five factors. Removing these items produced a shortened version, the WURS-45. We performed a logistic regression using actual factor loadings as well as factors based on item averages, and compared major depressive disorder (MDD) to generalized anxiety disorder (GAD) patients in the same analysis. We performed exploratory factor analysis with the WURS-45 items. We then performed logistic regressions and Receiver Operating Characteristics (ROC) analyses with the WURS-45 and WURS-25 factors. No increase in specificity or sensitivity arose when actual factors scores were used as opposed to factor scores from item averages. MDD and GAD ROC curves were very similar, supporting combining MDD with GAD patients into a single group. WURS-45 factors paralleled those derived from the full WURS. ROC curves, logistic regression and confusion tables showed the WURS-45 preserved the excellent diagnostic separation produced by the full WURS. Similar analyses showed WURS-25 scoring using its three factors improved its diagnostic utility. The WURS-45 has reduced redundancy with minimal loss in discriminatory power. Analysis of the WURS-25 using factor scores boosts its performance. Both versions of the scale provide clinical information describing childhood ADHD and are useful in separating adult patients with ADHD from those with MDD or GAD.

Wender Utah Rating Scale: Psychometrics, clinical utility and implications regarding the elements of ADHD.

The Wender Utah Rating Scale (WURS) is a self-report instrument completed by adults assessing a range of childhood symptoms and behaviors consistent with ADHD persisting into adulthood. Many items reflect emotional dysregulation. Although over 30 publications have examined its psychometric properties, reliance on non-clinical samples has limited conclusions from these reports, as have sub-optimal statistical approaches in most previous publications. None compared the full WURS to the abbreviated WURS-25. We evaluated both versions with adults presenting for treatment: 137 with ADHD and 230 with GAD or MDD, along with 120 normal controls. Factor analysis was performed on the full WURS using the clinical cohorts. The WURS versions were compared using ANOVA, logistic regression, ROC and confusion matrices. Consistent with two previous reports, the full WURS generated five factors: Disruptive mood & behavior, ADHD, Anxiety/dysphoria, Social and Academic. The ADHD factor correlated r > 0.8 with the Disruptive mood/behavior and the Academic factor. ADHD patients scored higher than GAD/MDD subjects (p < .001) on the Disruptive mood & behavior, ADHD, and Academic factors. The WURS-25 produced good separation of ADHD subjects from normal controls with ROC (AUC = 0.974) and logistic regression (Sensitivity = 91%, Specificity = 92%). Conversely, the full WURS better separated ADHD subjects from psychiatric controls with both ROC (AUC = 0.995) and logistic regression (Sensitivity = 84%, Specificity = 94%). Use of the full WURS with its five factors proved more successful at distinguishing ADHD from MDD and GAD than did the WURS-25. Its factors identify symptoms, including those of emotional dysregulation, critical to understanding ADHD.

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.

OROS methylphenidate in the treatment of adults with ADHD: a 6-month, open-label, follow-up study.

BACKGROUND: This open-label trial followed a previously reported randomized, placebo-controlled trial of osmotic release oral system (OROS) methylphenidate (MPH) for the treatment of personality disorder (PD). Important findings from the double-blind phase are reexamined for long-term significance. METHODS: Of 41 patients who completed the double-blind, placebo-controlled trial, 34 continued into this open-label phase. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) measured outcome. Patients were categorized using previously defined attention-deficit/hyperactivity disorder (ADHD) groups: ADHD alone, ADHD with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation plus oppositional symptoms (ADHD + ED + ODD); and 3 post hoc personality categories: patients with no PD (PD-negative), patients with 1 PD (PD-positive), and patients meeting criteria for 2 or more PDs (PD-plus). RESULTS: Three WRAADDS-defined ADHD dimensions improved at similar levels (attention + disorganization, 61%; hyperactivity + impulsivity, 60%; and emotional dysregulation, 66%). All ADHD subgroups (ADHD alone, ADHD + ED, and ADHD + ED + ODD) improved. ADHD + ED + ODD patients had the highest level of social maladjustment at baseline and showed the most long-term improvement in this area. PD-plus patients were less likely to complete the study or show improvement. Sixty-five percent of treatment responders were on moderate doses (< or =54 mg/d) of OROS MPH. Vital signs and ECGs did not differ from baseline. CONCLUSIONS: Eighteen (44%) patients completed the trial. All 3 ADHD dimensions showed similar, well-maintained improvement. Patients with several PDs responded poorly to treatment in this small trial.

Personality disorders in ADHD Part 3: Personality disorder, social adjustment, and their relation to dimensions of adult ADHD.

BACKGROUND: This study explored the relationship between the dimensions of adult attention-deficit/hyperactivity disorder (ADHD), personality disorder (PD), and adverse social adjustment. METHODS: In a controlled trial of osmotic release oral system methylphenidate, PD was assessed using the Wisconsin Personality Disorders Inventory IV (WISPI-IV), the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), and a final consensus diagnosis. Participants were categorized 2 ways: (1) ADHD alone, ADHD with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation plus oppositional symptoms (ADHD + ED + ODD); and (2) those with no PD (PD-negative), 1 (PD-positive), and 2 or more (PD-plus) PDs. RESULTS: None of the ADHD-alone patients had a PD compared with 33% of ADHD + ED patients and 68% of ADHD + ED + ODD patients. The level of ADHD-related emotional and oppositional symptoms correlated significantly with the severity of PD dimensions as assessed by WISPI-IV z scores and the number of items endorsed on the SCID-II screening questionnaire. Complex presentations (define by both ADHD and personality categories) were associated with high childhood ADHD ratings and problems in work, extended family, and economic functioning. CONCLUSION: The ADHD symptoms of emotional dysregulation and oppositional symptoms were associated with increased Axis II disorders. Adverse outcomes were concentrated in patients with ADHD combined with emotional and oppositional symptoms, and in those with comorbid PDs.

Personality disorder in ADHD Part 1: Assessment of personality disorder in adult ADHD using data from a clinical trial of OROS methylphenidate.

BACKGROUND: Comorbidity of personality disorder (PD) and attention-deficit/hyperactivity disorder (ADHD) has been suggested in several reports. However, assessment of PD is problematic, and studies have over-relied on baseline evaluations. METHODS: Forty-seven patients entered a double-blind trial of osmotic release oral system (OROS) methylphenidate (MPH). Patients were assessed at baseline with the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Following the study, all information-including tests, family reports, and extended clinical observations-produced a final PD diagnosis. Three post hoc categories were created: PD-negative (no PD), PD-positive (1 PD), and PD-plus (2 or more PDs). RESULTS: Twenty-one (45%) patients had a PD on the final assessment vs 62% using SCID-II and 33% using WISPI-IV; final PD diagnosis revealed 9% cluster A, 17% cluster B, and 28% cluster C. Twenty-one percent of patients experienced multiple disorders. Using a weighted kappa, the number of PDs on the final assessment correlated with the WISPI-IV (kappa=.53; P > .001) and the SCID-II (kappa =.70; P < .001). However the SCID-II overidentified and the WISPI-IV underidentified PD. CONCLUSION: Almost all PDs were represented in this sample, and past emphasis on cluster B appears unwarranted. Although the SCID-II and WISPI-IV had limited success in identifying specific PDs, they were more successful in identifying the number of PDs present in each patient. The small sample makes these findings preliminary.

Personality disorders in ADHD Part 2: The effect of symptoms of personality disorder on response to treatment with OROS methylphenidate in adults with ADHD.

BACKGROUND: This study explored the relationship between personality disorder (PD) and treatment response in a randomized, double-blind, clinical trial of osmotic release oral system (OROS) methylphenidate (MPH). METHODS: Forty-seven patients entered a crossover trial using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) to assess outcome. A final personality diagnosis was made using staff consensus and information from the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Three post hoc categories were created: PD-negative (no PD; n = 26), PD-positive (patients with 1 PD; n = 11), and PD-plus (patients with 2 or more PDs; n = 10). Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms was assessed using a mixed-model analysis with treatment and personality categories as fixed variables. Average z scores on the WISPI-IV and items endorsed on SCID-II provided dimensional measures of PD severity. RESULTS: Different treatment effects were observed for the PD subgroups (P < .001). PD-negative patients improved 40% on OROS MPH vs 7% on placebo, and PD-positive patients improved 66% on OROS MPH vs 9% on placebo. In contrast, PD-plus patients improved 26% on OROS MPH vs 23% on placebo. CONCLUSION: Most patients experienced significantly reduced ADHD symptoms on OROS MPH; however, patients with 2 or more PDs did not. The 2 alternate measures of PD supported this observation in this small exploratory study.

Types of Adult Attention-Deficit/Hyperactivity Disorder: A Replication Analysis.

OBJECTIVE: Research supports the importance of emotional symptoms in adults with attention-deficit/hyperactivity disorder (ADHD), which are not reflected in the DSM-5 or ICD-10 criteria. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) assesses these symptoms, plus inattention, hyperactivity, and impulsivity. This scale allowed us to divide adult ADHD into 2 subtypes in a 2015 publication: ADHD inattentive presentation and ADHD emotional dysregulation presentation. The present study refines this observation using a larger, more diverse sample. METHODS: Eight double-blind adult ADHD clinical trials (encompassing 1,490 subjects) were selected because they included assessment with the WRAADDS; a second, alternative ADHD measure; and the Clinical Global Impressions-Severity of Illness scale (CGI-S). These data were subjected to confirmatory factor analyses, and ADHD presentations were compared, including treatment response. RESULTS: The original factor structure fit poorly with these new data. However, an alternative 2-factor solution fit both the original and the new subjects. ADHD inattentive presentation (n = 774) was defined by the inattention factor, and ADHD emotional dysregulation presentation (n = 620) was defined by additional elevation of the emotional dysregulation factor. The proportion of ADHD emotional dysregulation presentation ranged from 25% to 73% across the 8 studies. The emotional dysregulation presentation was associated with both a greater severity as measured by the CGI-S (P < .001) and more manifestations of childhood ADHD as measured by the Wender Utah Rating Scale (P < .001). CONCLUSIONS: Factor analytic results supported the validity of 2 adult ADHD presentations based on levels of emotional dysregulation. This system offers a more clinically relevant approach to the diagnosis of ADHD in adults than does the DSM system.

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 approximately 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 approximately 470 nm account for the documented effectiveness of light therapy.

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.

Emotional dysregulation in adult ADHD and response to atomoxetine.

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.

Types of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate.

Much recent research describes the importance of emotional symptoms in ADHD. While there is no accepted system for including emotionality in diagnosing ADHD, the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) provides a tool to facilitate this. It assesses a range of adult ADHD symptoms which load on two factors: inattentive and emotional dysregulation. The consistently high inattentive factor was used to define significant elevation on the more variable emotional dysregulation factor (which contains four WRAADDS domains: hyperactivity/restlessness, temper, affective lability, and emotional over-reactivity) allowing the definition of two ADHD diagnostic types. We compared these two types on a broad range of adult subject characteristics, including response to methylphenidate (MPH) treatment assessed during two clinical trials. Marked impairment in three of the four emotional domains reflected a symptom severity level equivalent to that of the inattentive factor. 59 % met this threshold, defining them as ADHD emotion dysregulation presentation, as opposed to 41 % with ADHD inattentive presentation. Cluster analysis validated these groups by generating similar clusters with 85 % agreement regarding membership. ADHD emotional dysregulation presentation subjects showed more childhood ADHD symptoms, adult symptoms of oppositional defiant disorder, and evidence of personality disorder. Both types showed similar improvement during the double-blind MPH arm of the trials and during a 6-month open-label phase. Based on the presence of symptoms of emotional dysregulation, ADHD in adults can be conceptualized as two types. Impairment and comorbidity in adults with ADHD are largely concentrated in ADHD emotional dysregulation presentation patients.

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.

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.

Psychometric properties of the Wender-Reimherr Adult Attention Deficit Disorder Scale.

The Wender-Reimherr adult attention deficit disorder scale (WRAADDS; Wender, 1995) is a clinician-rated scale based on the Utah Criteria for attention-deficit/hyperactivity disorder (ADHD) in adults. It assesses ADHD symptom severity across 7 domains: attention difficulties, hyperactivity/restlessness, temper, affective lability, emotional over-reactivity, disorganization, and impulsivity. The normative sample consisted of 120 males and females ages 20-49 with no personal or family history of ADHD. Patients with ADHD met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) criteria, included males and females ages 20-60, and came from 5 clinical trials. Measures of reliability (test-retest r = .96; interrater r = .75) and internal consistency (Cronbach's alpha = 0.78) were acceptable. The WRAADDS correlated with the Conners' Adult ADHD Rating Scale (CAARS; Conners, Erhardt, & Sparrow, 1999) total scores (r = .501, p < .001). WRAADDS hyperactivity + impulsivity correlated with the CAARS hyperactivity/impulsivity (r = .601, p < .001), and WRAADDS attention + disorganization correlated with the CAARS inattention (r = .430, p < .001). Discriminate validity (adults with vs. without ADHD) was significant for all domains (p < .001). Factor analysis yielded a 2-factor solution accounting for 58% of the variance, one containing the emotional dimensions and the second containing attention and disorganization. Hyperactivity/restlessness and impulsivity were split between both factors. Changes in response to treatment for the WRAADDS and CAARS were highly correlated (p < .001). These psychometric data support continued use of the WRAADDS in adults with ADHD.

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.