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Background: Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder.Methods: The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response.Results: Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms.Conclusions: Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history. [ABSTRACT FROM AUTHOR]

Background: Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear. Methods: Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response. Results: Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses. Conclusions: An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment. Methods: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery‐Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors. Results: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial‐responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non‐responding class (9.7%) with sustained moderate‐severe depressive symptoms. Bipolar type I predicted membership of the non‐responding class and randomization to quetiapine predicted membership of either the responding or the non‐responding class. Conclusion: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate‐severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses. [ABSTRACT FROM AUTHOR]

Background: The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup.Methods: We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission.Results: Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P < .001) and after (37.2 ± 19.7 vs. 26.3 ± 18.0; P = .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with and without psychosis had similar course of symptom improvement and similar time to remission. There was no significant difference in the treatment outcomes of lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.Conclusion: Bipolar depressive episodes with psychotic features are more severe, and compared to nonpsychotic depressions, present a similar course of improvement. Given the small number of participants presenting psychosis, the lack of statistically significant difference between lithium- and quetiapine-based treatment of psychotic bipolar depressive episodes needs replication in a larger sample. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Many mood disorder patients need analgesics due to increased pain sensitivity. Recent studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit antidepressant treatment, which requires replication before clinical recommendations.Methods: The Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study randomized participants to 6 months lithium or quetiapine treatment. Use of NSAIDs and paracetamol was assessed throughout the study period and psychopathology measured with the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) and Bipolar Inventory of Symptoms Scale (BISS). The effects of NSAIDs and paracetamol on treatment outcome were examined using mixed effects linear regression adjusted for age, gender, body mass index, smoking status, exercise, and somatic diseases.Results: Among 482 participants, 177 (36.7%) used NSAIDs and/or paracetamol during the study. NSAID and paracetamol users did not differ from nonusers with respect to treatment outcome with lithium or quetiapine at any time point during 6 months treatment on the overall CGI-BP (β = 0.001 (95% CI = -0.01 to -0.01), P = .87), the BISS (β = 0.01 (95% CI = -0.17 to 0.15), P = .91), nor the CGI-BP subscales for depression or mania. Users of NSAIDs only (n = 76), paracetamol only (n = 62), and users of both NSAIDs and paracetamol (n = 39) showed no statistical difference compared to nonusers (all P > .3).Conclusions: This is the first trial to show that use of NSAIDs and paracetamol, alone or in combination, does not affect lithium- or quetiapine-based bipolar disorder mood-stabilizing treatment outcomes. Prior studies have suggested that NSAIDs may inhibit antidepressant treatment, whereas our results support findings indicating no detrimental effects of NSAIDs or paracetamol on affective disorder treatment. [ABSTRACT FROM AUTHOR]

Objective: Individuals with bipolar disorder experience a disproportionately high incidence of medical co-morbidity and obesity. These health-related problems are a barrier to recovery from mood episodes and have been linked with unfavorable responses to pharmacological treatment. However, little is known about whether and how these characteristics affect responses to adjunctive psychotherapy. Method: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy plus pharmacotherapy with collaborative care (a three-session psycho-educational intervention) plus pharmacotherapy. We conducted a post-hoc analysis to evaluate whether medical burden and body mass index predicted and/or moderated the likelihood of recovery and time until recovery from a depressive episode among patients in the two treatments. Results: Participants who had medical co-morbidity and body mass index data constituted 199 of the 293 patients in the original Systematic Treatment Enhancement Program for Bipolar Disorder trial. Higher medical burden predicted a lower likelihood of recovery from depression in both treatment conditions (odds ratio = 0.89), but did not moderate responses to intensive psychotherapy vs collaborative care. Intensive psychotherapy yielded superior recovery rates for individuals of normal body mass index (odds ratio= 2.39) compared with collaborative care, but not among individuals who were overweight or obese. Conclusion: Medical co-morbidity and body weight impacts symptom improvement and attention to this co-morbidity may inform the development of more personalized treatments for bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Little is known about predictors of recovery from bipolar depression.Aims: We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression.Method: A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n= 141) or a brief psychoeducational intervention (n= 111). All analyses were by intention-to-treat.Results: Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression.Conclusions: Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression. [ABSTRACT FROM AUTHOR]

Objective: People with bipolar disorder frequently have persistent symptoms, continued problems functioning and comorbid medical conditions. We propose applying the athletic coaching concept of marginal gains to help patients address these challenges to achieve wellness. Method: We review the concept of marginal gains and potential interventions to improve long-term outcomes for bipolar patients. Results: Evidence exists to help bipolar patients with diet and exercise, gradual behavioral change, mobile applications and peer support. Conclusion: Marginal gains, small and doable improvements across a broad range of areas, have great potential to improve the lives of people with bipolar disorder. [ABSTRACT FROM AUTHOR]

The article presents a study that compares the characteristics of individuals with bipolar disorder who sought psychotherapy with those who did not. Topics include a comparative effectiveness study of lithium versus quetiapine, a baseline assessment of participants' psychotherapy use within the past 3 months, mood, functioning, and overall health, and the under-utilization of adjunctive psychotherapies despite evidence that they are effective for mood stabilization and relapse prevention.

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. [ABSTRACT FROM AUTHOR]

Objectives The aims of this study were to evaluate correlates and predictors of life functioning and quality of life in bipolar disorder during a comparative effectiveness trial of moderate doses of lithium. Methods In the Lithium treatment moderate-dose use study (LiTMUS), 283 symptomatic outpatients with bipolar disorder type I or II were randomized to receive lithium plus “optimal personalized treatment (OPT)”, or OPT alone. Participants were assessed using structured diagnostic interviews, clinician-rated blinded assessments, and questionnaires. We employ linear mixed effects models to test the effect of treatment overall and adjunct lithium specifically on quality of life or functioning. Similar models are used to examine the association of baseline demographics and clinical features with quality of life and life functioning. Results Quality of life and impaired functioning at baseline were associated with lower income, higher depressive severity, and more psychiatric comorbid conditions. Over 6 months, patients in both treatment groups improved in quality of life and life functioning ( p- Values<0.0001); without a statistically significant difference between the two treatment groups ( p- Values>0.05). Within the lithium group, improvement in quality of life and functioning was not associated with concurrent lithium levels at week 12 or week 24 ( p -Values>0.05). Lower baseline depressive severity and younger age of onset predicted less improvement in functioning over 6 months. Conclusions Optimized care for bipolar disorder improves overall quality of life and life functioning, with no additional benefit from adjunct moderate doses of lithium. Illness burden and psychosocial stressors were associated with worse quality of life and lower functioning in individuals with bipolar disorder. [ABSTRACT FROM AUTHOR]

Abstract: Background: Individuals with bipolar disorder lead a sedentary lifestyle associated with worse course of illness and recurrence of symptoms. Identifying potentially modifiable predictors of exercise frequency could lead to interventions with powerful consequences on the course of illness and overall health. Methods: The present study examines baseline reports of exercise frequency of bipolar patients in a multi-site comparative effectiveness study of a second generation antipsychotic (quetiapine) versus a classic mood stabilizer (lithium). Demographics, quality of life, functioning, and mood symptoms were assessed. Results: Approximately 40% of participants reported not exercising regularly (at least once per week). Less frequent weekly exercise was associated with higher BMI, more time depressed, more depressive symptoms, and lower quality of life and functioning. In contrast, more frequent exercise was associated with experiencing more mania in the past year and more current manic symptoms. Limitations: Exercise frequency was measured by self-report and details of the exercise were not collected. Analyses rely on baseline data, allowing only for association analyses. Directionality and predictive validity cannot be determined. Data were collected in the context of a clinical trial and thus, it is possible that the generalizability of the findings could be limited. Conclusion: There appears to be a mood-specific relationship between exercise frequency and polarity such that depression is associated with less exercise and mania with more exercise in individuals with bipolar disorder. This suggests that increasing or decreasing exercise could be a targeted intervention for patients with depressive or mood elevation symptoms, respectively. [Copyright &y& Elsevier]

Objective: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT). Method: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone. The primary outcome measures were the Clinical Global Impression Scale for Bipolar Disorder-Severity (CGI-BP-S) and "necessary clinical adjustments" (medication adjustments per month). Secondary outcome measures included mood symptoms and functioning. The authors also assessed sustained remission (defined as a CGI-BP-S score 2 ≤ for 2 months) and treatment with second-generation antipsychotics. The authors hypothesized that lithium plus OPT would result in greater clinical improvement and fewer necessary clinical adjustments. Results: The authors observed no statistically significant advantage of lithium plus OPT on CGI-BP-S scores, necessary clinical adjustments, or proportion with sustained remission. Both groups had similar outcomes across secondary clinical and functional measures. Fewer patients in the lithium-plus-OPT group received secondgeneration antipsychotics compared with the OPT-only group (48.3% and 62.5%, respectively). Conclusions: In this pragmatic comparative effectiveness study, a moderate but tolerated dosage of lithium plus OPT conferred no symptomatic advantage when compared with OPT alone, but the lithium-plus-OPT group had less exposure to second-generation antipsychotics. Only about onequarter of patients in both groups achieved sustained remission of symptoms. These findings highlight the persistent and chronic nature of bipolar disorder as well as the magnitude of unmet needs in its treatment. [ABSTRACT FROM AUTHOR]

Background: Pharmacotherapy is the first line of treatment for bipolar disorder, but many patients continue to experience persistent subthreshold symptoms. Alternative adjunct treatments, including nutritional therapies, may have the potential to alleviate residual symptoms and improve the outcomes of standard pharmacotherapy. The aim of this paper is to critically review the current clinical evidence and mechanisms of action of nutrient-based therapies alone or in combination with commonly used pharmacotherapies for mania and bipolar depression. Methods: We conducted a Medline search for clinical trials conducted with humans, published in English from 1960 to 2012 using nutritional supplements such as n-3, chromium, inositol, choline, magnesium, folate and tryptophan alone or in combination with pharmacotherapies for the treatment of bipolar disorder. Results: Preliminary data yields conflicting but mainly positive evidence for the use of n-3 fatty acids and chromium in the treatment of bipolar depression. Limited evidence found that inositol may be helpful for bipolar depression, but larger sample sizes are needed. Preliminary randomized, controlled trials suggest that choline, magnesium, folate and tryptophan may be beneficial for reducing symptoms of mania. Conclusions: Given the potential public health impact of identifying adjunct treatments that improve psychiatric as well as physical health outcomes, nutritional treatments appear promising for the management of bipolar disorder but require further study. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We sought to address how predictors and moderators of psychotherapy for bipolar depression - identified individually in prior analyses - can inform the development of a metric for prospectively classifying treatment outcome in intensive psychotherapy (IP) versus collaborative care (CC) adjunctive to pharmacotherapy in the Systematic Treatment Enhancement Program (STEP-BD) study.Methods: We conducted post-hoc analyses on 135 STEP-BD participants using cluster analysis to identify subsets of participants with similar clinical profiles and investigated this combined metric as a moderator and predictor of response to IP. We used agglomerative hierarchical cluster analyses and k-means clustering to determine the content of the clinical profiles. Logistic regression and Cox proportional hazard models were used to evaluate whether the resulting clusters predicted or moderated likelihood of recovery or time until recovery.Results: The cluster analysis yielded a two-cluster solution: 1) "less-recurrent/severe" and 2) "chronic/recurrent." Rates of recovery in IP were similar for less-recurrent/severe and chronic/recurrent participants. Less-recurrent/severe patients were more likely than chronic/recurrent patients to achieve recovery in CC (p=.040, OR=4.56). IP yielded a faster recovery for chronic/recurrent participants, whereas CC led to recovery sooner in the less-recurrent/severe cluster (p=.034, OR=2.62).Limitations: Cluster analyses require list-wise deletion of cases with missing data so we were unable to conduct analyses on all STEP-BD participants.Conclusions: A well-powered, parametric approach can distinguish patients based on illness history and provide clinicians with symptom profiles of patients that confer differential prognosis in CC vs. IP. [ABSTRACT FROM AUTHOR]

• Among 592 patients with bipolar depression, initial non-response was high. • Among patients with non-response after 6 weeks, only one-third eventually responded by 24 weeks. • The findings did not improve among patients with additional guideline-based treatment. We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response. We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinically indicated. We report cumulative proportions of response (>50% improvement in MADRS) and remission (MADRS<10). We included 592 participants with bipolar depression (mean 39 years, 59% female, mean MADRS 25). Among 393 (66%) participants without response after 2 weeks, 46% responded by 24 weeks; for 291 (49%) without response at 4 weeks, 40% responded and 33% remitted by 24 weeks; for 222 (38%) without a response at 6 weeks, 36% responded and 29% remitted by 24 weeks; for 185 (31%) without a response at 8 weeks, 29% responded and 24% remitted by 24 weeks. Rates were similar for participants who had started an additional mood-stabilizing drug during the first 6 or 8 weeks. Among patients with bipolar depression and non-response after 6 weeks treatment, representing an adequate bipolar depression trial, only one-third responded by 24 weeks. These results highlight the need for better treatment alternatives for non-responders to evidence-based treatments for bipolar depression. [ABSTRACT FROM AUTHOR]

Background: Successful medication management for bipolar disorder requires clinicians to monitor and adjust regimens as needed, to achieve maximum effectiveness and patient adherence. This study aims to measure the prevalence of indications for medication adjustment at visits for bipolar disorder treatment; the frequency with which physicians recommend medication adjustments; and how strongly the indications predict the adjustments.Methods: Data included 3,094 visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that compared treatment with lithium versus quetiapine. A set of indications for adjustment was matched to reports of whether the physician recommended a medication adjustment at that visit, and what type. Associations between indication and adjustment were examined using bivariate tests and hierarchical logistic mixed effects models.Results: Medication adjustment was recommended at 63% of the visits where one of the indications was present, and at 53% of all visits. In multivariable analyses, adjustment was more likely to be recommended if there was an indication of non-response or side effects, for patients who started on quetiapine rather than lithium, or for patients who were female, married, employed or more educated.Limitations: The study's cross-sectional design implies that observed associations could result from confounding variables. Also, the CHOICE trial placed certain restrictions on physicians' medication choices, although this is not likely to have resulted in major alterations of prescribing patterns.Conclusions: Clinical inertia may help explain the lack of any adjustment recommendation at 37% of the visits where one of the indications was present. Other explanations could also apply, such as watchful waiting. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti–triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders.Methods: Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response.Results: Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms.Limitations: This was a pilot feasibility and acceptability trial; results should be interpreted with caution.Conclusions: Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder requires psychiatric medications, but even guideline-concordant treatment fails to bring many patients to remission or keep them euthymic. To address this gap, researchers have developed adjunctive psychotherapies. The purpose of this paper is to critically review the evidence for the efficacy of manualized psychosocial interventions for bipolar disorder.Methods: We conducted a search of the literature to examine recent (2007-present), randomized controlled studies of the following psychotherapy interventions for bipolar disorder: psychoeducation (PE), cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy (IPSRT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and family therapies such as family focused therapy (FFT).Results: All of the psychotherapy interventions appear to be effective in reducing depressive symptoms. Psychoeducation and CBT are associated with increased time to mood episode relapse or recurrence. MBCT has demonstrated a particular effectiveness in improving depressive and anxiety symptoms. Online psychotherapy interventions, programs combining one or more psychotherapy interventions, and targeted interventions centering on particular symptoms have been the focus of recent, randomized controlled studies in bipolar disorder.Conclusions: Psychotherapy interventions for the treatment of bipolar disorder have substantial evidence for efficacy. The next challenge will to disseminate these psychotherapies into the community. [ABSTRACT FROM AUTHOR]

Background: Affective symptoms and medical comorbidities have a negative impact on the course of bipolar disorder. The aim of this analysis was to examine how the perceptions of physical health and functioning in individuals with bipolar disorder relate to their mood symptoms.Methods: We analyzed longitudinal data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) on the physical subscales of the Short Form Health Survey (SF-36) (physical functioning, role limitations due to physical problems, bodily pain, and general health).Results: Participants' perception of their overall physical health predicted severity of mania/hypomania, depression, and life satisfaction at concurrent and future visits. Perceptions of role limitations due to physical health problems predicted depressive symptoms and poor life satisfaction. Worse bodily pain predicted symptoms of mania/hypomania. Reports of specific or concrete physical limitations in daily life showed no associations with psychiatric symptoms at concurrent assessments, but did predict worse course of illness one year later. SF-36 scores showed significant, but small associations with the presence of medical comorbidities.Limitations: Perceptions of physical health and quality of life were self-report, potentially lending themselves to transient negative biases, particularly among depressed participants. Additionally, the SF-36 was selected as a generic, widely used measure; as a result, it was not specific to the illness burden of bipolar disorder.Conclusion: Overall, broad perceptions of poor physical health were associated with worse course of illness over the 24 months of the study. Though further research is warranted, changes in subjective physical health related quality of life, even independent of objective health changes, may offer important insight into global wellbeing and be targets of psychotherapy treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders. Methods: The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses. Results: Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders. Limitations: This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use. Conclusions: Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II disorder over 6 months, after controlling for potential confounding factors. [Copyright &y& Elsevier]