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OBJECTIVES: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. METHODS: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived higher versus lower function as the dependent variable and selected clinical and demographic variables as predictors. RESULTS: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. CONCLUSIONS: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia. Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Conclusions: Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD. [ABSTRACT FROM AUTHOR]

Objectives: The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE‐II‐Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC). Methods: Psychiatric symptoms, socio‐demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD‐RC) and without (BD‐NRC) RC were compared. Results: Of 726 BD patients, 159 (21.9%) met DSM‐5 criteria for RC. BD‐RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007). Conclusions: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs. [ABSTRACT FROM AUTHOR]

Objectives: In healthy populations, caffeine appears to have beneficial effects on health; however, patients with bipolar disorder (BD) are routinely advised to limit caffeine use in psychoeducation programmes. We aimed to examine all literature reporting whether caffeine intake/withdrawal impacts the natural course of BD, in terms of clinical outcomes. Methods: PubMed, Embase and PsycINFO were searched (up to 17/07/2020) and all studies reporting data on individuals with BD comparing a measure of caffeine use with illness severity (symptoms of mania, depression, psychosis, anxiety, sleep or suicidality) were included. Results: Of the 1678 records reviewed, 17 studies met inclusion criteria (10 case reports, 1 retrospective cohort study, 5 cross‐sectional studies, 1 interventional study). Most case reports described people with BD switching to manic, hypomanic or mixed states after consuming caffeine in variable amounts and/or whose serum lithium concentrations increased after reducing caffeine consumption. The interventional study found that caffeine may suppress lithium concentrations, while the retrospective cohort study reported that participants who drank coffee had more suicidality than non‐drinkers. Conclusions: The literature examining clinical effects of caffeine in patients with BD is not conclusive. Acute increases in caffeine consumption may precede the occurrence of manic symptoms in patients with BD, potentially through a direct stimulant effect, affecting sleep patterns and/or the metabolism of lithium or other medications, although increases in caffeine intake could also be a consequence of an ongoing manic relapse or a prodromal sign. Further research is needed to determine whether caffeine use impacts the long‐term prognosis of BD. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive remediation therapy (CRT) may benefit people with bipolar disorder type I and II for whom cognitive impairment is a major contributor to disability. Extensive research has demonstrated CRT to improve cognition and psychosocial functioning in people with different diagnoses, but randomised trials of evidenced therapy programmes are lacking for bipolar disorders. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. Methods: This proof‐of‐concept, single‐blind randomised trial recruited participants aged 18‐65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment‐as‐usual (TAU) with or without individual CRT for 12 weeks. The partly computerised CRT programme ("CIRCuiTS") was therapist‐led and is evidence‐based from trials in those with psychotic illnesses. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention‐to‐treat analyses. Trial registration: ISRCTN ID32290525. Results: Sixty participants were recruited (02/2016‐06/2018) and randomised to CRT (n = 29) or TAU (n = 31). Trial withdrawals were equivalent (CRT n = 2/29; TAU n = 5/31). CRT satisfaction indicated high acceptability. Intention‐to‐treat analyses (N = 60) demonstrated greater improvements for CRT‐ than TAU‐randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in the following domains (week 25 effect sizes reported here): IQ (SES = 0.71, 95% CI [0.29,1.13]), working memory (SES = 0.70, 95% CI [0.31,1.10]), executive function (SES = 0.93, 95% CI [0.33,1.54]), psychosocial functioning (SES = 0.49, 95% CI [0.18,0.80]) and goal attainment (SES = 2.02, 95% CI [0.89,3.14]). No serious adverse events were reported. Conclusions: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof‐of‐concept trial encourage further investigation in a definitive trial. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder (BD) suffer from cognitive deficits across several domains. The association between cognitive performance and psychosocial functioning has led to the emergence of cognition as a treatment target. Objective: This study reviews the existing literature on cognitive enhancement interventions for people with BD, focusing on different treatment approaches and methodological quality. Methods: We conducted a systematic search following the PRISMA guidelines. Sample characteristics and main outcomes for each study and treatment characteristics for each approach were extracted. Study quality was assessed using the Clinical Trials Assessment Measure (CTAM) and Cochrane Collaboration's Risk of Bias tool by independent raters. Results: Eleven articles reporting data from seven original studies were identified encompassing 471 participants. Two treatment approaches were identified, cognitive and functional remediation. For controlled studies, methodological quality was modest (average CTAM score = 60.3), while the overall risk of bias was considered moderate. Beneficial effects on cognitive or functional outcomes were reported in the majority of studies (91%), but these findings were isolated and not replicated across studies. Key methodological limitations included small sample sizes, poor description of randomization process, high attrition rates, and participant exclusion from the analysis. Conclusions: Findings are promising but preliminary. Quality studies were few and mostly underpowered. Heterogeneity in sample characteristics, outcome measures, and treatment approaches further limit the ability to generalize findings. Adequately powered trials are required to replicate initial findings, while moderators of treatment response and mechanisms of transfer need to be explored. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Make lithium great again - Precisely! 2019; 7 (1). 4 Scott J, Etain B, Bellivier F. Can an integrated science approach to precision medicine research improve lithium treatment in bipolar disorders? Before highlighting factors that may optimise lithium use, we wish to remind readers that lithium is cheap, uniquely effective and a prime candidate for developing precision prescribing in psychiatry. [Extracted from the article]

We agree in general with Malhi et al's forthright Editorial "Make Lithium Great Again", where they reiterate that, despite its clear efficacy and effectiveness, lithium remains under-utilized in the treatment of bipolar disorder. In the UK, lithium monotherapy is recommended as first line long-term pharmacological therapy for bipolar disorder by the British Association for Psychopharmacology Guidelines.2 Despite this, prescribing of lithium in the UK appears to be decreasing. A recent national (Scottish) linkage study found only 5.90% of patients on long-term pharmacological therapy for bipolar disorder received lithium monotherapy between 2009 and 2016. [Extracted from the article]