Objective: To assess the efficacy, safety, and tolerability of cariprazine in the treatment of the depressed phase of bipolar I disorder in adults (NCT02670538).Methods: In this phase 3 double‐blind placebo‐controlled study, adult patients with bipolar I disorder according to the Diagnostic and Statistical Manual — 5th Edition criteria and a current depressive episode were randomized to placebo (n = 167), cariprazine 1.5 mg/day (n = 168) or cariprazine 3.0 mg/day (n = 158). Efficacy parameters were changes in the Montgomery‐Åsberg Depression Rating Scale (MADRS) total scores (primary) and Clinical Global Impressions — Severity (CGI‐S) scores (secondary) from baseline to Week 6 compared to placebo. A mixed‐model for repeated measures was used to estimate the least‐squares mean differences (LSMD); P‐values were adjusted for multiplicity. Adverse events (AEs), laboratory results, vital signs, and suicide risk were monitored.Results: Cariprazine 1.5 mg/day significantly reduced depressive symptoms on the primary (MADRS LSMD = −2.5; adjusted P = .0417) and secondary (CGI‐S LSMD = −0.3; adjusted P = .0417) efficacy parameters vs placebo; differences were not statistically significant for cariprazine 3.0 mg/day. Common treatment‐emergent AEs (≥5% in either cariprazine group and at least twice the incidence of placebo) were akathisia, restlessness, nausea, and fatigue. Mean metabolic parameter changes were low and generally comparable among groups; mean weight increases were ≤0.5 kg for all groups.Conclusions: Cariprazine 1.5 mg/day significantly reduced depressive symptoms in adults with bipolar I depression compared to placebo, but differences were not significant for cariprazine 3.0 mg/day. The safety and tolerability profiles were similar to previous studies of cariprazine.

Aims: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations.Methods: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved.Results: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence‐based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey.Conclusions: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60‐0.80 mmol/L with the option to reduce it to 0.40‐0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80‐1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40‐0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65‐79 years, and to maximally 0.70 mmol/L over age 80 years.

Background: This study explores the association of demographic and clinical features with quality of life and functioning in individuals with bipolar disorder. Methods: Adult participants (N = 482) with bipolar I or II disorder were enrolled in a comparative effectiveness study across eleven study sites and completed baseline measures of medical and psychiatric history, current mood, quality of life, and functioning. Participants with at least mildly depressive or manic/hypomanic symptomatic severity were randomized to receive lithium or quetiapine in addition to adjunctive personalized treatment for 6 months. Results: Participants with more severe depressive and irritability symptoms had lower quality of life and higher functional impairment. All psychiatric comorbid conditions except substance use disorder were associated with worse quality of life. On average, females had lower quality of life than males. Patients who were married, living as married, divorced, or separated had worse functional impairment compared with patients who were single or never married. A composite score of social disadvantage was associated with worse functioning and marginally associated with worse quality of life. Symptom severity did not moderate the effect of social disadvantage on quality of life or functioning. Conclusions: Our findings highlight that depression, irritability, and psychiatric comorbid conditions negatively impact quality of life and functioning in bipolar disorder. The study suggests that individuals with social disadvantage are at risk for functional impairment. Trial Registration This study is registered with ClinicalTrials.gov. Identification number: NCT01331304