Psychotic symptoms during bipolar depressive episodes and suicidal ideation.

BACKGROUND: Psychotic symptoms during bipolar depressive episodes, especially in outpatients, are under recognized and studied by clinicians and researchers. We examined the relationship between psychotic symptoms during a depressive episode and suicidal ideation in bipolar patients. METHODS: Participants (N = 351) were adult, depressed outpatients with bipolar disorder (BD) in a comparative effectiveness study of quetiapine versus lithium. Psychotic symptoms were assessed via Bipolar Inventory of Signs and Symptoms Scale (BISS) and depressive episodes via Mini-International Neuropsychiatric Interview (MINI). Because only 4.84% (N = 17) endorsed psychotic symptoms, we performed iterative multivariate matching with non-psychotic participants. On every matched population, a multiple regression analysis examined whether psychotic symptoms were associated with suicidal ideation, via the Concise Health Risk Taking scale (CHRT-12). RESULTS: Averaged across the 50 matched populations, current psychotic symptoms predicted active suicidal ideation on the CHRT, but not a passive propensity toward suicide or total CHRT scores, after adjusting for common correlates of suicidality (e.g., previous suicidal behavior) (ß=0.59, p=.01, R2= 0.41). LIMITATIONS: Our study was limited by three factors. First, the generalizability of our study was limited as the sample included only outpatients. Next, the analysis was cross-sectional and does not allow for causal interpretation. Lastly, our study lacked information regarding the content and mood congruency of participants' psychosis. CONCLUSION: While a small proportion of BD outpatients had current symptoms of psychosis during their depressive episode, those who did were more likely to endorse active suicidal thoughts, including suicide methods and plans.

An evaluation of suicidal risk in bipolar patients with comorbid posttraumatic stress disorder.

BACKGROUND: While bipolar disorder (BD) and posttraumatic stress disorder (PTSD) frequently co-occur and individually have a higher risk of suicide compared to the general population, few studies have examined the impact of comorbid PTSD on suicidal ideation in patients with BD. METHODS: We analyzed baseline data from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for bipolar disorder study (Bipolar CHOICE), a 6-month, pharmacological comparative effectiveness trial of individuals with BD. Bipolar CHOICE enrolled 482 individuals. A hierarchical multiple regression analysis assessed whether comorbid PTSD was associated with increased suicidal ideation as assessed by the Concise Health Risk Tracking Scale (CHRT) total and factor scores, while controlling for common correlates of suicidal ideation in this population such as a current major depressive episode, comorbid anxiety disorders, severity of illness and previous suicide attempts. RESULTS: Consistent with our hypothesis, diagnosis of comorbid PTSD was a significant predictor of the CHRT total score (ß=2.59, p=.03). Comorbid PTSD was also a significant predictor of the CHRT propensity factor (ß=2.32, adjusted p=.04), but was not a significant predictor of the active suicidal thoughts factor. Additionally, all participants with comorbid PTSD (N = 58) endorsed current suicidal ideation (p=.005) and were more likely to have had a previous suicide attempt (p<.001) compared to those without PTSD. LIMITATIONS: Generalizability beyond outpatient settings is limited, mixed affective states were not assessed, and analyses were cross-sectional. CONCLUSIONS: Patients have an increased risk of suicidal ideation when PTSD is comorbid with BD.

The impact of binge eating behavior on lithium- and quetiapine-associated changes in body weight, body mass index, and waist circumference during 6 months of treatment: Findings from the bipolar CHOICE study.

BACKGROUND: Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. METHODS: We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. RESULTS: On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 = 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p = 0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only, F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating. LIMITATIONS: Bipolar CHOICE was not designed to study anthropometric outcomes. CONCLUSIONS: Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

Clinical applications of transcranial magnetic stimulation in bipolar disorder.

BACKGROUND: Many patients with bipolar disorder (BD) fail to experience benefit following traditional pharmacotherapy, necessitating alternative treatment options that will enable such patients to achieve remission. Transcranial magnetic stimulation (TMS) is a relatively new, noninvasive neuromodulation technique that involves the application of magnetic pulses on hyperactive or hypoactive cortical brain areas. We evaluated the existing literature on TMS as a treatment for BD across varied mood states. METHODS: We searched PubMed up to October 2018 for original data articles published in English that evaluated outcomes in a bipolar sample across depressive, manic, mixed, and maintenance phases of BD. RESULTS: Clinical trials of TMS for BD particularly suggest the potential of repetitive TMS for reducing depressive symptoms. Studies of TMS for mania have yielded more mixed findings. Few studies have evaluated TMS in other phases of the bipolar illness. TMS is generally associated with mild side effects though, in a few studies, it has been shown to contribute to a manic switch in previously depressed bipolar patients. CONCLUSIONS: Transcranial magnetic stimulation is a promising approach for treating patients with BD who have failed to respond to pharmacological or psychosocial treatment. Future research should more clearly elucidate which TMS protocols may be most effective for a given bipolar patient.

Bipolar depression and suicidal ideation: Moderators and mediators of a complex relationship.

INTRODUCTION: Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. METHODS: 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. RESULTS: Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. LIMITATIONS: Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. DISCUSSION: Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

Transcranial magnetic stimulation in anxiety and trauma-related disorders: A systematic review and meta-analysis.

BACKGROUND: Transcranial magnetic stimulation (TMS) has been evaluated as an effective treatment option for patients with major depressive disorder. However, there are limited studies that have evaluated the efficacy of TMS for other neuropsychiatric disorders such as anxiety and trauma-related disorders. We reviewed the literature that has evaluated TMS as a treatment for anxiety and trauma-related disorders. METHODS: We searched for articles published up to December 2017 in Embase, Medline, and ISI Web of Science databases, following the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles (n = 520) evaluating TMS in anxiety and trauma-related disorders were screened and a small subset of these that met the eligibility criteria (n = 17) were included in the systematic review, of which nine evaluated TMS in posttraumatic stress disorder (PTSD), four in generalized anxiety disorder (GAD), two in specific phobia (SP), and two in panic disorder (PD). The meta-analysis was performed with PTSD and GAD since PD and SP had an insufficient number of studies and sample sizes. RESULTS: Among anxiety and trauma-related disorders, TMS has been most widely studied as a treatment for PTSD. TMS demonstrated large overall treatment effect for both PTSD (ES = -0.88, 95% CI: -1.42, -0.34) and GAD (ES = -2.06, 95% CI: -2.64, -1.48), including applying high frequency over the right dorsolateral prefrontal cortex. Since few studies have evaluated TMS for SP and PD, few conclusions can be drawn. CONCLUSIONS: Our meta-analysis suggests that TMS may be an effective treatment for GAD and PTSD.

Treating Circadian Rhythm Disruption in Bipolar Disorder.

PURPOSE OF REVIEW: Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian dysfunction in BD. RECENT FINDINGS: Targeted social rhythm therapy may be useful for bipolar depression though some studies suggest that a non-targeted psychosocial or pharmacological intervention may be just as efficacious. Lithium holds potential for addressing circadian dysfunction in BD. Blue-blocking therapy may be useful for mania and midday bright light therapy may relieve depression. CONCLUSIONS: Psychosocial, pharmacological, and light-based approaches are promising avenues for treating circadian dysfunction in BD.

Tachyphylaxis in major depressive disorder: A review of the current state of research.

BACKGROUND: Patients with major depressive disorder (MDD) often experience a re-emergence or worsening of symptoms despite ongoing treatment with previously effective antidepressant pharmacotherapy. This lost or reduced antidepressant response during maintenance, referred to as tachyphylaxis, negatively impacts treatment outcomes and quality of life for patients with MDD. This review assesses the prevalence of antidepressant tachyphylaxis as well as the evidence for interventions to manage it. METHODS: We searched PubMed/Medline for the relevant clinical trials and meta-analyses on antidepressant tachyphylaxis up to January 2017. Search terms included "depression" paired with "treatment" (n = 186,674), "tachyphylaxis" paired with "depression" (n = 112), "tachyphylaxis" paired with "major depressive disorder" (n = 21), and "antidepressant" paired with "tachyphylaxis" (n = 68). Studies were included if they reported on a clinical trial or meta-analysis exploring tachyphylaxis in MDD and were excluded if the sample population did not have a primary DSM diagnosis of MDD. RESULTS: Rates of tachyphylaxis varied from 9% to 57% depending on the patient population and duration of follow-up. Limited evidence suggests potentially beneficial strategies for managing tachyphylaxis, including change in antidepressant dosing, switch of class of antidepressant medication, augmentation or combination pharmacotherapy, and psychotherapy. LIMITATIONS: Studies of antidepressant tachyphylaxis are largely heterogeneous in nature and employ strict inclusion/exclusion criteria; thus, these findings may not be generalizable to all depressed populations. CONCLUSION: Few established treatment strategies exist to manage antidepressant tachyphylaxis. Further interventional research is needed to provide symptomatic relief for patients with tachyphylaxis in MDD.

Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale.

BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

Substance use comorbidity in bipolar disorder: A qualitative review of treatment strategies and outcomes.

BACKGROUND AND OBJECTIVES: Substance use disorders (SUDs) are present in up to 70% of patients with bipolar disorder (BD) and contribute to high rates of disability, morbidity, and treatment non-adherence. Despite this prevalence, few trials have investigated targeted psychosocial interventions for comorbid BD and SUDs. METHODS: Using PubMed and PsycINFO, we conducted a search of the literature up to January 2018 for psychosocial interventions targeted to patients with comorbid BD and SUDs. We identified eight total trials. Of these studies, four randomized and two open trials targeted the types of substance use (alcohol and illicit drugs) of primary concern to mood stability; the remaining two studies, both open trials, targeted smoking cessation. RESULTS: None of the randomized trials provided consistent evidence for management of both mood symptoms and substance use though integrated group therapy (IGT) demonstrated consistent beneficial effects on substance use outcomes. Other treatments showed benefit for mood symptoms without benefits for alcohol or illicit substance use. Small pilot studies of combined treatments for smoking cessation provided some initial promise. CONCLUSIONS: At present, IGT is the most-well validated and efficacious approach if substance use is targeted in an initial treatment phase. For a subsequent phase, additional psychosocial BD treatments may be needed for mood and functioning benefits. SCIENTIFIC SIGNIFICANCE: This review synthesizes the psychosocial interventions that have been conducted in comorbid BD and SUDs while also providing a perspective on which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. (Am J Addict 2018;27:188-201).

Medication disposal practices: Increasing patient and clinician education on safe methods.

Recent research suggests that the nation's water supply is contaminated with trace pharmaceuticals that exert a negative environmental and public health impact. Incorrect medication disposal methods (e.g. flushing medications down the toilet or drain) are a significant factor contributing to the presence of medication compounds in the aquatic environment. In this commentary, we provide a summary of the existing data on pharmaceuticals in the nation's water as well as the role of improper medication disposal methods on water contamination. We discuss statistics on improper medication disposal practices among patients and clinicians as well as recent advances in proper medication disposal methods as a solution to this problem. Currently, many patients and clinicians are not aware of proper medication disposal practices. We summarize the importance of patient and clinician education in advancing environmental-safe medication disposal methods.

Sleep disturbance may impact treatment outcome in bipolar disorder: A preliminary investigation in the context of a large comparative effectiveness trial.

BACKGROUND: Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium. METHODS: The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18-70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes. RESULTS: 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38-0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03). LIMITATIONS: Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure. CONCLUSIONS: Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.

L-Methylfolate For Bipolar I depressive episodes: An open trial proof-of-concept registry.

BACKGROUND: L-methylfolate is a compelling candidate to treat bipolar I major depressive episodes. While approved as an adjunct for unipolar major depressive disorder, no studies have been done to assess the tolerability, safety, and efficacy of L-methylfolate for bipolar depression. As a first step, we developed a registry of bipolar patients treated with L-methylfolate to examine tolerability and outcomes. METHODS: Subjects (N=10) received treatment as usual plus daily L-methylfolate 15mg for 6 weeks in this open-label registry. Depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and manic symptoms with the Young Mania Rating Scale (YMRS). Effect size was measured with Cohen's d to provide an estimate of potential efficacy. RESULTS: The pre-treatment mean (SD) MADRS score was 23.4 (4.34); the post-treatment score was 13.9 (8.24). Cohen's d was 1.19. At post-treatment, 6/10 patients had at least 50% MADRS improvement, and 4/10 patients exhibited remission with MADRS≤10. The pre-treatment YMRS score was 3.2 (3.0); the post-treatment score was 2.7 (5.2). Cohen's d was 0.17. LIMITATIONS: This registry was a small open-label clinical trial for a fluctuating disorder. We cannot rule out that our results are due to regression to the mean. A controlled trial is warranted. CONCLUSIONS: This first proof-of-concept open registry suggests that L-methylfolate in combination with treatment as usual has potential to treat bipolar depression.

Tracking medication changes to assess outcomes in comparative effectiveness research: A bipolar CHOICE study.

BACKGROUND: Comparative effectiveness research uses multiple tools, but lacks outcome measures to assess large electronic medical records and claims data. Aggregate changes in medications in response to clinical need may serve as a surrogate outcome measure. We developed the Medication Recommendation Tracking Form (MRTF) to record the frequency, types, and reasons for medication adjustments in order to calculate Necessary Clinical Adjustments (NCAs), medication adjustments to reduce symptoms, maximize treatment response, or address problematic side effects. METHODS: The MRTF was completed at every visit for 482 adult patients in Bipolar CHOICE, a 6-month randomized comparative effectiveness trial. RESULTS: Responders had significantly fewer NCAs compared to non-responders. NCAs predicted subsequent response status such that every additional NCA during the previous visit decreased a patient's odds of response by approximately 30%. Patients with more severe symptoms had a greater number of NCAs at the subsequent visit. Patients with a comorbid anxiety disorder demonstrated a significantly higher rate of NCAs per month than those without a comorbid anxiety disorder. Patients with greater frequency, intensity, and interference of side effects had higher rates of NCAs. Participants with fewer NCAs reported a higher quality of life and decreased functional impairment. LIMITATIONS: The MRTF has not been examined in community clinic settings and did not predict response more efficiently than the Clinical Global Impression-Bipolar Version (CGI-BP). CONCLUSIONS: The MRTF is a feasible proxy of clinical outcome, with implications for clinical training and decision-making. Analyses of big data could use changes in medications as a surrogate outcome measure.

Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder.

BACKGROUND: Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA. METHOD: Within the duration of the study (September 2010-September 2013), participants with bipolar I or II disorder (DSM-IV-TR) were randomized for 6 months to receive lithium (n = 240) or quetiapine (n = 242). Lithium and quetiapine were combined with other medications for bipolar disorder consistent with typical clinical practice (adjunctive personalized treatment [APT], excluding any SGA for the lithium + APT group and excluding lithium or any other SGA for the quetiapine + APT group). Coprimary outcome measures included Clinical Global Impressions-Efficacy Index (CGI-EI) and necessary clinical adjustments, which measured number of changes in adjunctive personalized treatment. Secondary measures included a full range of symptoms, cardiovascular risk, functioning, quality of life, suicidal ideation and behavior, and adverse events. RESULTS: Participants improved across all measures, and over 20% had a sustained response. Primary (CGI-EI, P = .59; necessary clinical adjustments, P = .15) and secondary outcome changes were not statistically significantly different between the 2 groups. For participants with greater manic/hypomanic symptoms, CGI-EI changes were significantly more favorable with quetiapine + APT (P = .02). Among those with anxiety, the lithium + APT group had fewer necessary clinical adjustments per month (P = .02). Lithium was better tolerated than quetiapine in terms of the burden of side effects frequency (P = .05), intensity (P = .01), and impairment (P = .01). CONCLUSIONS: Despite adequate power to detect clinically meaningful differences, we found outcomes with lithium + APT and quetiapine + APT were not significantly different across 6 months of treatment for bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

Baseline disability and poor functioning in bipolar disorder predict worse outcomes: results from the Bipolar CHOICE study.

OBJECTIVE: To examine the effects of treatment on functioning impairments and quality of life and assess baseline functioning and employment status as predictors of treatment response in symptomatic individuals from the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (Bipolar CHOICE) study. METHOD: Bipolar CHOICE was an 11-site, 6-month randomized effectiveness study comparing lithium to quetiapine, each with adjunctive personalized treatments (APTs). We examined post hoc (1) the effects of treatment on functioning, (2) how changes in functioning differed between treatment responders and nonresponders, and (3) whether functioning and employment status mediated treatment response in 482 participants with DSM-IV-TR bipolar I or II disorder from September 2010 to September 2013. RESULTS: Treatment was associated with significant improvements in functioning and quality of life, regardless of treatment group (P values < .0001). Responders showed greater improvements in quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire P values < .05) and functioning (Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool P values < .05) than nonresponders. Unemployed or disabled participants at baseline had significantly greater illness severity at baseline than employed participants (P values < .05). Over the study duration, employed participants reported greater improvements in physical health and quality of life in leisure activities than both unemployed and disabled participants (P values < .05). Individuals who saw greater improvement in functioning and quality of life tended to show greater improvements in depressive and anxiety symptoms (P values ≤ .0001), as well as overall illness severity (P values < .001). Early (8 weeks) and very early (4 weeks) clinical changes in mood symptoms predicted changes in functioning and quality of life at 6 months (P values < .001). CONCLUSIONS: Prior disability status was associated with a worse treatment response and prospective illness course. Results implicate functioning and employment status as important markers of illness severity and likelihood of recovery in bipolar disorder, suggesting that interventions that target functional impairment may improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

A tool to predict suicidal ideation and behavior in bipolar disorder: The Concise Health Risk Tracking Self-Report.

BACKGROUND: Few brief, self-report measures exist that can reliably predict adverse suicidality outcomes in patients with BD. This study utilized the Concise Health Risk Tracking Self-Report (CHRT) to assess suicidality in patients with BD and examined its psychometric performance, clinical correlates, and prospective value in predicting adverse events related to suicidality. METHODS: The CHRT was administered at baseline and follow-up to 482 adult patients in Bipolar CHOICE, a 6-month randomized comparative effectiveness trial. The Columbia Suicide Severity Rating Scale (CSSRS) was used at baseline to assess lifetime history of suicide attempts and related behaviors. Clinician-rated measures of mood (Bipolar Inventory of Symptoms Scale) and bipolar symptoms (Clinical Global Impressions-Bipolar Version) were conducted at baseline and follow-up. RESULTS: The CHRT showed excellent internal consistency and construct validity and was highly correlated with clinician ratings of depression, anxiety, and overall functioning at baseline and throughout the study. Baseline CHRT scores significantly predicted risk of subsequent suicidality-related Serious Adverse Events (sSAEs), after controlling for mood and comorbidity. Specifically, the hazard of a sSAE increased by 76% for every 10-point increase in baseline CHRT score. Past history of suicide attempts and related behaviors, as assessed by the CSSRS, did not predict subsequent sSAEs. LIMITATIONS: The CSSRS was used to assess static risk factors in terms of past suicidal behaviors and may have been a more powerful predictor over longer-term follow-up. CONCLUSIONS: The CHRT offers a quick and robust self-report tool for assessing suicidal risk and has important implications for future research and clinical practice.

Psychotherapy use in bipolar disorder: Association with functioning and illness severity.

OBJECTIVE: This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. METHODS: Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants' psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups. RESULTS: Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. CONCLUSIONS: These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden.

Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE).

OBJECTIVES: Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity. METHODS: The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence). RESULTS: We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides. CONCLUSIONS: There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.

A randomized, double-blind, placebo-controlled phase 2 study of the augmentation of a nicotinic acetylcholine receptor partial agonist in depression: is there a relationship to leptin levels?

This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an α4ß2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI for 8 weeks, subjects with a Hamilton Depression Scale 17 score greater than or equal to 16 were entered into a double-blind phase and randomized to CP-601,927 2 mg twice daily or placebo for 6 weeks. The primary end point was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from double-blind baseline to week 14. There was no significant difference in change from baseline to week 14 in the MADRS score for CP-610,927 versus placebo (least square mean difference [80% confidence interval], -1.30 [-3.32-0.71]). Post hoc analyses revealed that the drug-placebo difference in change from baseline (SE) to week 14 in MADRS score was greater in subjects with body mass index (BMI) less than or equal to 35 kg/m (-3.43 [1.87], P = 0.069) than those with BMI greater than 35 kg/m (3.37 [2.8], P = 0.230). Analysis of biomarkers associated with increased BMI suggests that baseline leptin had a significant effect on treatment outcome. P values for the effect of treatment on mean change in MADRS score for subjects with baseline leptin levels below and above the median were 0.055 and 0.0055, respectively. CP-601,927 was equivalent to placebo as an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to SSRIs. However, post hoc analyses suggest that BMI, particularly elevated leptin levels, may have affected the response to CP-601,927; however, further study may be needed to confirm these results.