Association of history of adverse childhood experiences with irritable bowel syndrome (IBS) in individuals with mood disorders.

The objective of the current study was to assess the association between adverse childhood experiences (ACEs) and irritable bowel syndrome (IBS) in mood disorder patients. Self-report data from the International Mood Disorders Collaborative Project were cross-sectionally analyzed to compare rates of IBS in participants with confirmed diagnoses of major depressive disorder (MDD; n = 279) or bipolar disorder (BD; n = 219). Data was sub-grouped and compared based on history of ACEs. In total, 69 of the 498 participants reported a diagnosis of IBS (13.8%). BD was associated with significantly elevated rates of IBS compared to MDD (18.5% versus 10.1% respectively). After adjusting for age and sex, history of childhood sexual abuse was associated with increased rates of IBS in mood disorder participants [adjusted odds ratio (aOR) = 1.95]. In the MDD subgroup, ACEs (all categories and individual categories) were not associated with increased rates of IBS. In the BD subgroup, history of childhood sexual abuse was associated with significantly increased rates of IBS (38% versus 14%; aOR = 3.7). In summary, BD was associated with a higher prevalence of IBS compared to MDD. Additionally, history of sexual abuse was associated with an increased prevalence of IBS in BD, but not in MDD.

Is binge eating a cognitive disorder? Results from the International Mood Disorders Collaborative Project.

BACKGROUND: Individuals with binge eating disorder (BED) are differentially affected by attention-deficit/hyperactivity disorder (ADHD), obesity, and substance use disorder. We have investigated to what extent cognitive deficits are relevant to binge eating behavior (BEB). METHODS: Data from the International Mood Disorders Collaborative Project were retrospectively and cross-sectionally analyzed to compare individuals with and without BEB on measures of anhedonia and general cognitive functions (n = 566). BEB was assessed using items from the Mini International Neuropsychiatric Interview Plus 5.0.0 for DSM-IV-TR that correspond with DSM-5-defined diagnostic criteria for BED. Individuals currently prescribed benzodiazepines were excluded from analyses. RESULTS: Individuals with BEB were more likely to exhibit anhedonia (P = .044) and general cognitive (P = .005) symptoms, when compared to those without BEB. We also observed that individuals with BEB were more likely to have specific psychiatric (eg, ADHD) and medical (eg, obesity) disorders (P < .05). CONCLUSIONS: Our results suggest that a central disturbance in cognitive processes may be mechanistically relevant to the cause and treatment of BEB in adults.

The prevalence and clinical characteristics associated with Diagnostic and Statistical Manual Version-5-defined anxious distress specifier in adults with major depressive disorder: results from the International Mood Disorders Collaborative Project.

OBJECTIVES: The aim of the study was to evaluate the prevalence of and illness characteristics in adults with major depressive disorder (MDD) with anxious distress specifier (ADS) enrolled in the International Mood Disorders Collaborative Project, which is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada and the Cleveland Clinic, Cleveland, Ohio, USA. METHODS: Data from participants who met criteria for a current major depressive episode as part of MDD (n = 830) were included in this post hoc analysis. Diagnostic and Statistical Manual Version-5-defined ADS was operationalized as the presence of at least two out of three proxy items instead of two out of five specifiers. RESULTS: A total of 464 individuals (i.e. 56%) met criteria for ADS. There were no between-group differences in sociodemographic variables (e.g. gender, employment, marital status). Greater severity of illness was observed in adults with ADS as evidenced by a higher number of hospitalizations, higher rates of suicidal ideation, greater depressive symptom severity, greater workplace impairment, decreased quality of life, and greater self-reported cognitive impairment. CONCLUSIONS: Our findings underscore the importance of evaluating ADS in adults with MDD as its presence identifies a subpopulation with greater illness-associated burden and hazards.

Binge eating in adults with mood disorders: Results from the International Mood Disorders Collaborative Project.

A post hoc analysis was conducted using data from participants (N=631) with a DSM-IV-TR defined diagnosis of major depressive disorder (MDD) or bipolar disorder (BD) who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. It was determined that 20.6% of adults with mood disorders as part of the IMDCP fulfilled criteria for binge eating behaviour (BE). A higher percentage of individuals with BD met criteria for BE when compared to MDD (25.4% vs. 16%; p=0.004) Univariate analyses indicated that individuals with a mood disorder (i.e., MDD or BD) and BE had greater scores on measures of anxiety severity (p=0.013) and higher rates of lifetime and current substance dependence, lifetime alcohol abuse (p=0.007, p=0.006, and p=0.015, respectively), Attention Deficit Hyperactivity Disorder (ADHD) (p=0.018) and measures of neuroticism (p=0.019). Individuals with a mood disorder and concurrent BE had lower scores on measures of conscientiousness (p=0.019). Individuals meeting criteria for BE were also significantly more likely to be obese (i.e., BMI≥30kg/m2) (50% vs. 25.5%; p<0.001). Binge eating is common amongst adults utilising tertiary care services principally for a mood disorder. The presence of BE identifies a subset of adults with mood disorders who have greater illness complexity as evidenced by course of illness variables and comorbidity. Screening for BE amongst individuals with mood disorders is warranted; parsing neurobiological substrates subserving non-homeostatic eating behaviour amongst individuals with mood disorders is a future research vista.

Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project.

BACKGROUND: Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. METHOD: A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. RESULTS: A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). CONCLUSIONS: These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

The impact of cognitive impairment on perceived workforce performance: results from the International Mood Disorders Collaborative Project.

BACKGROUND: Cognitive dysfunction and depression severity are key mediators of workplace adjustment in adults with major depressive disorder (MDD). Herein, we sought to determine the extent to which measures of depression severity and cognitive dysfunction were associated with perceived global disability, workplace performance and quality of life. METHOD: A post hoc analysis was conducted using data from 260 participants with a diagnosis of DSM-IV-TR-defined MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. Measures of workplace function, global disability, depression severity, cognitive function, and quality of life were employed. These data were analyzed using a multiple variable linear regression equations. RESULTS: Perceived global disability was significantly predicted by clinical ratings of depression severity (ß=0.54), and perceived inattention (ß=0.24), accounting for 37% of the variance. In addition, perceived inattention (ß=0.58) and clinical ratings of depression severity (ß=0.18), were also significant predictors of perceived workplace productivity/performance, accounting for 38% of the variance. Finally, both clinical ratings of depression severity (ß=-0.54), and perceived inattention (ß=-0.18) were significant inverse predictors of perceived quality of life, accounting for 34% of the variance. CONCLUSION: The overarching finding in the analysis herein is that workplace performance variability is explained by subjective measures of cognitive dysfunction to a greater extent than total depression symptom severity. Conversely, total depression symptom severity accounts for a greater degree of variability in global measures of disability relative to cognitive measures. Treatment strategies for adults with major depressive disorder should address issues of cognitive dysfunction to improve workforce participation and performance.

The prevalence and illness characteristics of DSM-5-defined "mixed feature specifier" in adults with major depressive disorder and bipolar disorder: Results from the International Mood Disorders Collaborative Project.

BACKGROUND: A substantial proportion of individuals with mood disorders present with sub-syndromal hypo/manic features. The objective of this analysis was to evaluate the prevalence and illness characteristics of the Diagnostic and Statistical Manual Version-5 (DSM-5) - defined mixed features specifier (MFS) in adults with major depressive disorder (MDD) and bipolar disorder (BD). METHOD: Data from participants who met criteria for a current mood episode as part of MDD (n=506) or BD (BD-I: n=216, BD-II: n=130) were included in this post-hoc analysis. All participants were enrolled in the International Mood Disorders Collaborative Project (IMDCP): a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto and the Cleveland Clinic, Cleveland, Ohio. Mixed features specifier was operationalized as a score ≥ 1 on 3 or more select items on the Young Mania Rating Scale (YMRS) or ≥ 1 on 3 select items of the Montgomery Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAMD-17) during an index major depressive episode (MDE) or hypo/manic episode, respectively. RESULTS: A total of 26.0% (n=149), 34.0% (n=65), and 33.8% (n=49) of individuals met criteria for MFS during an index MDE as part of MDD, BD-I and BD-II, respectively. Mixed features specifier during a hypo/manic episode was identified in 20.4% (n=52) and 5.1% (n=8) in BD-I and BD-II participants, respectively. Individuals with MDE-MFS as part of BD or MDD exhibited a more severe depressive phenotype (p=0.0002 and p<0.0002, respectively) and reported a higher rate of alcohol/substance use disorder in the context of BD but not MDD (p=0.002). Individuals with MFS were more likely to have co-existing heart disease suggestive of a distinct pattern of comorbidity and neurobiology. LIMITATIONS: Data were post-hoc and obtained from individuals utilizing a university-based mood disorder centre which may affect generalizability. CONCLUSIONS: Diagnostic and Statistical Manual Version-5-defined MFS is common during an MDE as part of MDD and BD. The presence of MFS identifies a subgroup of individuals with greater illness complexity and possibly a higher rate of cardiovascular comorbidity. The results herein underscore the common occurrence of MFS in adults with either BD or MDD. Moreover, the results of our analysis indicate that adults with mood disorders and MFS have distinct clinical characteristics and comorbidity patterns.

The effect of personality dimensions on functional outcomes in mood disorders.

INTRODUCTION: Functional impairment associated with mood disorders may be related to a characteristic "profile" of normative personality dimensions. METHODS: Individuals (age ≥ 18 years) with MDD (n = 400) or BD (n = 317), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), were enrolled in the IMDCP. Personality was evaluated with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and functionality with the Sheehan Disability Scale and Endicott Work Productivity Scale. Path analysis using linear multiple regressions was performed to identify direct and indirect effects of personality on functional impairment. RESULTS: Lower conscientiousness exerted a significant direct effect on global (p = 0.017) and family life dysfunction in individuals with MDD (p = 0.002), as well as lower work productivity in both MDD (p = 0.020) and BD (p = 0.018). Lower extraversion exerted a significant direct effect on social impairment in individuals with BD (p = 0.017). Higher neuroticism and agreeableness as well as lower extraversion exerted indirect effects on global and social dysfunction in individuals with MDD via their effects on depression severity. In BD, higher neuroticism and openness indirectly affected global dysfunction. Family dysfunction was indirectly affected by higher neuroticism and openness as well as lower extraversion in MDD and BD. CONCLUSION: The results suggest that discrete personality dimensions may exert direct and indirect effects on functional outcomes in individuals with mood disorders. Personalizing disease management approaches in mood disorders with emphasis on vocational rehabilitation may benefit from measurement and intervention targeting personality.

The association between childhood adversity and components of metabolic syndrome in adults with mood disorders: results from the international mood disorders collaborative project.

OBJECTIVE: We sought to determine whether a reported history of childhood adversity is associated with components of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III)-defined metabolic syndrome in adults with mood disorders. METHOD: This was a cross-sectional analysis of adult outpatients (N = 373; n = 230 female, n = 143 male; mean age [SD] = 42.86 [14.43]) from the International Mood Disorders Collaborative Project (University of Toronto and Cleveland Clinic) with DSM-IV-defined major depressive disorder and bipolar I/II disorder. Childhood adversity was measured with the Klein Trauma & Abuse-Neglect self-report scale. The groups with and without childhood adversity were compared to determine possible differences in the rates of metabolic syndrome and its components. Logistic and linear regressions adjusted for age, sex, education, employment status, and smoking were used to evaluate the association between childhood adversity and components of metabolic syndrome. RESULTS: For the full sample, 83 subjects (22.25%) met criteria for metabolic syndrome. Individuals reporting a history of any childhood adversity had higher systolic and diastolic blood pressure (systolic: p = 0.040; diastolic: p = 0.038). Among subjects with a history of sexual abuse, a significant proportion met criteria for obesity (45.28% vs. 32.88%; p = 0.010); a trend toward overweight was found for subjects with a history of physical abuse (76.32% vs. 63.33%; p = 0.074), although this relationship did not remain significant after adjusting for potential confounders. There was no statistically significant difference in the overall rate of dyslipidemia and/or metabolic syndrome between subjects with and without childhood adversity. CONCLUSION: The results herein provide preliminary evidence suggesting that childhood adversity is associated with metabolic syndrome components in individuals with mood disorders.

Admixture analysis of age at onset in major depressive disorder.

OBJECTIVES: This study aimed to determine the distributions of the age at onset (AAO) in patients with major depressive disorder (MDD) using admixture analysis and to determine the clinical differences between subgroups with different AAO. METHODS: Participants were administered the Mini-International Neuropsychiatric Interview to obtain clinical data. Admixture analysis was performed using the STATA module DENORMIX to identify subgroups characterized by differences in AAO. RESULTS: The best fit model was the three-component model with the following means, standard deviations and proportions: 14.60 (3.75) years (49.1%), 29.15 (6.75) years (34.1%) and 46.96 (6.06) years (16.8%) (χ(2)=3.64, 2 df, P=.162). The three subgroups were divided by AAO of 22 and 40. After controlling for duration of illness, there were no significant differences between the three AAO subgroups in terms of gender and psychiatric family history. However, the early-onset subgroup was significantly more likely to report being single compared to the intermediate- and late-onset groups. The proportion of individuals meeting criteria for lifetime comorbid panic disorders and obsessive-compulsive disorder did not differ significantly between the AAO groups. However, the early-onset group reported a higher incidence of attention-deficit/hyperactivity disorder (5.1% vs. 1.7% and 1.2%, P=.086), although this was not statistically significant. CONCLUSIONS: Our study identified three characteristically different AAO subgroups in individuals suffering from MDD. The subgroups may reflect different underlying neurobiological mechanisms involved.

Effects of electroconvulsive therapy on brain functional activation and connectivity in depression.

OBJECTIVE: Past neuroimaging work has suggested that increased activation to cognitive and emotional tasks and decreased connectivity in frontal regions are related to cognitive inefficiency in depression; normalization of these relationships has been associated with successful treatment. The present study investigated brain function before and after electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD) and demonstrated the effect of treatment on cortical activation patterns. METHODS: Six ECT-naive patients with depression (mean ± SD age, 39.0 ± 5.4 years) were treated with ECT. Within 1 week before and 1 to 3 weeks after ECT, the patients underwent a magnetic resonance imaging session with functional magnetic resonance image scanning during working memory and affective tasks and during rest. Changes in voxelwise statistical maps of brain response to each task in regions identified to be relevant from past studies of depression were compared with changes in depression severity as measured by the Hamilton Depression Rating Score. Changes in functional connectivity between brain regions were also compared with changes in depression severity. RESULTS: Activation during both tasks was generally found to be decreased after ECT. Remission of depression was significantly associated with reduced affective deactivation after ECT in the orbitofrontal cortex (P = 0.03). Whole-brain functional connectivity of the anterior cingulate cortex showed a consistent increase in connectivity to the right dorsolateral prefrontal cortex and posterior cingulate cortex after ECT. CONCLUSIONS: These results suggest that successful ECT for MDD is associated with decreased activation to cognitive and emotional tasks and an increase in resting connectivity.

A large pharmacy claims-based descriptive analysis of patients with migraine and associated pharmacologic treatment patterns.

PURPOSE: To investigate drug use, prescribing patterns, and comorbidities among patients with migraine in a large pharmacy claims database. METHODS: 104,625 migraine subjects (identified according to the criteria in the International Classification of Diseases, Ninth Revision [ICD-9] for migraine or migraine-specific acute medication use) and an equal number of control patients were selected from a de-identified claims database; the prevalence of patients with migraine-specific claims was determined. Patient demographics, migraine-related medication use, other psychotropic medication use, and comorbidities over a 12-month period were compared between the migraine population and the control group and between migraine subgroups. RESULTS: Of the study population, 3.5% had a migraine diagnosis according to the ICD-9 or received a migraine-specific acute medication. Compared with controls, migraine patients had significantly greater disease comorbidity and higher use of prescription nonsteroidal anti-inflammatory drugs and controlled painkillers; they were also more likely to receive medications used to prevent migraines and other nonmigraine psychotropic medications, such as anxiolytics and hypnotics. Among migraine patients, 66% received acute migraine-specific medication while only 20% received US Food and Drug Administration-approved migraine preventive therapy. Notably, one-third of high triptan users did not receive any kind of preventive medication. Multiple medical and psychiatric comorbidities were observed at higher rates among migraine sufferers. In addition to significantly higher utilization of antidepressants compared with controls, migraine patients also received significantly more other psychotropic drugs by a factor of 2:1. CONCLUSION: Acute migraine medications are commonly used and frequently dispensed at rates that raise concern of overuse; high use is often seen without any preventive medications. Furthermore, use of US Food and Drug Administration-approved preventive medications is low. Finally, patients with migraine are significantly more likely to receive other psychotropic medications. These findings suggest efforts to optimize the management of migraines could address appropriate use of triptans, increased and more effective use of migraine preventive medications, and better understanding of the use of other psychotropics.

Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study.

OBJECTIVE: To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania. METHOD: Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5-40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate. RESULTS: The mean change in YMRS total score from baseline to endpoint was -23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia. CONCLUSIONS: These preliminary results suggest that olanzapine monotherapy is effective and relatively safe in patients with treatment-resistant bipolar mania. Randomized, double-blind, placebo-controlled study is warranted.

Rate of non-adherence prior to upward dose titration in previously stable antidepressant users.

BACKGROUND: Non-adherence to antidepressant medications is a contributing factor to disease relapse and may result in needless increases in antidepressant dosing. METHODS: We analyzed de-identified patient claims data from Medco Health Solutions, Inc.'s information database and measured adherence as the medication possession ratio (MPR), with adequate adherence as MPR ≥80%. Adherence was calculated for patients in whom antidepressants were dose escalated and who were on the same antidepressant medication for at least 180 days before the upward dosage titration. Statistical analysis was performed on subgroups comparing adherence with mail vs. retail channels, differences in age and gender, generic prescription vs. brand only, and prescription by psychiatrist vs. non-psychiatrist. RESULTS: 29.7% of patients were non-adherent to their antidepressant medication during the 6 months prior to a prescribed increase in dosage. Non-adherence was significantly lower among patients using the Medco Therapeutic Resource Centers® mail order vs. retail channel. Younger age correlated with poorer adherence. Rates of non-adherence were also significantly greater among women, those receiving generic medications, and among patients with overall lower disease comorbidity. Adherence was not significantly impacted by prescription from a psychiatrist or a non-psychiatrist. LIMITATIONS: Retrospective design and use of an administrative patient claims database. CONCLUSIONS: Suboptimal medication adherence commonly precedes an upward dosage titration of antidepressant medications. Utilization of a mail order channel may improve adherence. Clinicians prescribing antidepressants should explore adherence issues carefully prior to recommending an increase in dosage.

Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naive bipolar I or II depression: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To conduct an exploratory evaluation of the acute efficacy of extended-release divalproex sodium compared to placebo in patients with bipolar I or II depression. METHOD: Outpatients aged 18-70 years with mood stabilizer-naive bipolar I or II disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 6 weeks of divalproex sodium monotherapy or placebo. The primary outcome measure was mean change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included rates of response and remission, changes in the Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores, and changes in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale. The study was conducted between 2003 and 2007. RESULTS: Fifty-four subjects with bipolar I (n = 20) or bipolar II (n = 34) disorder were randomly assigned to divalproex or placebo; 67% (36 of 54) met DSM-IV criteria for rapid cycling. Divalproex treatment produced statistically significant improvement in MADRS scores compared with placebo from week 3 onward. The proportions of patients meeting response criteria were 38.5% (10 of 26) in the divalproex group versus 10.7% (3 of 28) for the placebo group (P = .017). The proportions of patients meeting remission criteria were 23.1% (6 of 26) for divalproex versus 10.7% (3 of 28) for placebo (P = .208). Subgroup analysis revealed no separation between divalproex and placebo for those with bipolar II diagnoses. Nausea, increased appetite, diarrhea, dry mouth, and cramps were the most common side effects. CONCLUSIONS: These data suggest that divalproex sodium is efficacious and reasonably well tolerated in the acute treatment of mood stabilizer-naive patients with bipolar depression, particularly for those with rapid-cycling type I presentations, and that confirmatory large-scale studies are indicated. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00194116.

Adjunctive aripiprazole for depression: predictive value of early assessment.

OBJECTIVES: To determine whether early symptom improvement with adjunctive aripiprazole in major depressive disorder (MDD) predicts overall symptom remission. STUDY DESIGN: Post hoc pooled analysis of 3 randomized, double-blind studies evaluating efficacy, safety, and tolerability of adjunctive aripiprazole or placebo with standard antidepressant therapy (ADT) in inadequate responders to a prospective 8-week ADT and at least 1 historical ADT. METHODS: A multivariate logistic regression model was developed to determine factors predicting remission most strongly at the end point. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 10 or less at end point. RESULTS: Early improvement in depression symptoms was the most significant predictor of remission. In adjunctive aripiprazole and placebo groups, improvement of 20% or more in MADRS total score (week 2) was a significant predictor of remission. At week 2, high sensitivity and high negative predictive values (NPVs) were reported for remission in both treatment arms. In the adjunctive aripiprazole arm, early improvement predicted later MADRS remission with high sensitivity (88.0%) and a high NPV (91.5%). Positive predictive value was moderate in both the adjunctive aripiprazole (45.4%) and placebo (37.5%) arms; specificity was 55.0% with adjunctive aripiprazole and 71.5% with placebo. CONCLUSIONS: Week 2 was a clinically meaningful time point to identify early improvers, and lack of improvement early in treatment was a highly significant predictor of lack of later remission. Early assessment of changes in symptoms could prove useful in clinical practice and more appropriately target healthcare costs.

Attention-deficit/hyperactivity disorder in adults with bipolar disorder or major depressive disorder: results from the international mood disorders collaborative project.

OBJECTIVE: Relatively few studies have evaluated the clinical implications of lifetime attention-deficit/hyperactivity disorder (ADHD) in adults with bipolar disorder or major depressive disorder (MDD). Herein, we sought to determine the prevalence as well as the demographic and clinical correlates of lifetime ADHD in persons with a mood disorder. METHOD: The first 399 patients enrolled in the International Mood Disorders Collaborative Project (IMDCP) were evaluated for lifetime ADHD using the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus) as the primary instrument to derive current and lifetime DSM-IV diagnoses. All analyses of variables of interest were conducted utilizing the MINI-Plus, the Adult ADHD Self-Report Scale-v1.1, and the Wender Utah Rating Scale-Short Form. The effect of ADHD on clinical presentation, course of illness variables, comorbidity, anamnesis, treatment, and outcome are reported. The IMDCP is a joint initiative of the Mood Disorders Psychopharmacology Unit at the University Health Network, University of Toronto, Toronto, Ontario, Canada, and the Cleveland Clinic Center for Mood Disorders Treatment and Research at Lutheran Hospital, Cleveland, Ohio. All data for this study were procured between January 2008 and January 2009. RESULTS: The percentages of subjects with MDD or bipolar disorder meeting the DSM-IV criteria for lifetime adult ADHD were 5.4% and 17.6% (P < .001), respectively. Lifetime comorbid ADHD in both mood disorder populations was associated with earlier age at illness onset (MDD, P = .049; bipolar disorder, P = .005), a higher number of psychiatric comorbidities (eg, MDD and current panic disorder with agoraphobia [P = .002]; bipolar disorder and social phobia [P = .012]), and decreased quality of life (MDD, P = .018). CONCLUSIONS: The overarching findings herein are that the adult ADHD phenotype is commonly reported by individuals with MDD or bipolar disorder and is associated with a greater illness burden and complexity.

Fibromyalgia and bipolar disorder: a potential problem?

OBJECTIVE: To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder. METHODS: A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI) to assess for functional capacity. RESULTS: A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ >or= 7); 78.12% were clinically depressed (BDI >or= 10); and 52.13% reported daytime sleepiness (ESS >or= 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001]. CONCLUSIONS: We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.

Quetiapine XR efficacy and tolerability as monotherapy and as adjunctive treatment to conventional antidepressants in the acute and maintenance treatment of major depressive disorder: a review of registration trials.

Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 - 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.