Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs.

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey.

Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study.

Objective: Cariprazine, a dopamine D/D and 5-HT receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.

Methods: In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.

MoodNetwork: An Innovative Approach to Patient-centered Research.

Introduction: Research has often been viewed as a passive process by which participants enroll in studies developed by researchers. It is becoming clearer that to understand the nuances of mood episodes and how to prevent them, we need to conduct large clinical trials that have the power to investigate moderators and mediators, or catalysts and mechanisms of change. MoodNetwork, the first online, patient-centered research community for individuals with mood disorders, aims to change the way that traditional research has been conducted by involving patients, their caregivers, and advocates in the process of research.

Prevalence and predictors of physician recommendations for medication adjustment in bipolar disorder treatment.

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 pilot study of minocycline for the treatment of bipolar depression: Effects on cortical glutathione and oxidative stress in vivo.

Background: The antibiotic minocycline appears to promote neuroprotection through antioxidant and other mechanisms that may be relevant to the pathophysiology of bipolar disorder. The present study assessed the efficacy of minocycline in bipolar depression and examined the association between minocycline treatment and brain glutathione (GSH), an essential regulator of oxidative stress.

Method: Twenty patients with bipolar disorder experiencing acute depressive symptoms enrolled in an 8-week, open-label trial of adjuvant minocycline.

Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review.

Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19.

Behavioral Indicators on a Mobile Sensing Platform Predict Clinically Validated Psychiatric Symptoms of Mood and Anxiety Disorders.

Background: There is a critical need for real-time tracking of behavioral indicators of mental disorders. Mobile sensing platforms that objectively and noninvasively collect, store, and analyze behavioral indicators have not yet been clinically validated or scalable.

Objective: The aim of our study was to report on models of clinical symptoms for post-traumatic stress disorder (PTSD) and depression derived from a scalable mobile sensing platform.

Predictive analytics in mental health: applications, guidelines, challenges and perspectives.

The emerging field of 'predictive analytics in mental health' has recently generated tremendous interest with the bold promise to revolutionize clinical practice in psychiatry paralleling similar developments in personalized and precision medicine. Here, we provide an overview of the key questions and challenges in the field, aiming to (1) propose general guidelines for predictive analytics projects in psychiatry, (2) provide a conceptual introduction to core aspects of predictive modeling technology, and (3) foster a broad and informed discussion involving all stakeholders including researchers, clinicians, patients, funding bodies and policymakers.

Testing for clinical inertia in medication treatment of bipolar disorder.

Background: Clinical inertia has been defined as lack of change in medication treatment at visits where a medication adjustment appears to be indicated. This paper seeks to identify the extent of clinical inertia in medication treatment of bipolar disorder. A second goal is to identify patient characteristics that predict this treatment pattern.

Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder.

Objective: Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD).

The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study.

Objective: Both preclinical studies and clinical trials have indicated that the combination of a selective serotonin reuptake inhibitor (SSRI) and a statin may have superior antidepressant effects compared with SSRI treatment alone. The authors sought to assess whether this beneficial effect can be generalized to a more heterogeneous population of SSRI users.

Method: In a nationwide cohort study that included all incident SSRI users in Denmark between 1997 and 2012, the authors compared people who had periods of concomitant use of SSRIs and statins with people who had periods of SSRI treatment alone.

Getting to wellness: The potential of the athletic model of marginal gains for the treatment of bipolar disorder.

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.

The Role of Anger/Hostility in Treatment-Resistant Depression: A Secondary Analysis From the ADAPT-A Study.

Major depressive disorder is often accompanied by elevated levels of anger, hostility, and irritability, which may contribute to worse outcomes. The present study is a secondary analysis examining the role of anger/hostility in the treatment response to low-dose aripiprazole added to antidepressant therapy in 225 patients with major depressive disorder and inadequate response to antidepressant treatment. Repeated-measures model demonstrated no drug-placebo difference in treatment response across levels of anger/hostility.

Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.

Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders.

An exploratory study of responses to low-dose lithium in African Americans and Hispanics.

Objectives: Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS).

Methods: LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs.

The Bipolarity Index: a clinician-rated measure of diagnostic confidence.

Background: The Bipolarity Index is a clinician-rated scale that rates cardinal features of the disorder across five domains: signs and symptoms, age of onset, course of illness, response to treatment, and family history. We tested the Index in routine clinical practice to identify the optimal cut-off for distinguishing bipolar from non-bipolar disorders.

Method: Sequential patients in a private practice were rated with the Bipolarity Index (n=1903) at intake.

Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.

Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia and major depression, and a haplotype located in an intronic region of the L-type voltage-gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant.

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

Background: Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment.

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.