Bipolar disorder (BD) often necessitates hospitalization, especially during manic episodes. Long-acting injectable antipsychotics (LAIs) are theorized to enhance treatment adherence and decrease rehospitalization rates compared to oral medications. This study aimed to evaluate the real-world effectiveness of LAIs in reducing rehospitalizations among BD patients admitted for bipolar mania.

We conducted a retrospective cohort study using data from a tertiary psychiatry hospital in Taiwan spanning January 1st, 2006, to December 31st, 2017. We analyzed 2212 hospitalizations among 945 patients with bipolar mania. A mixed-effects Cox regression model compared rehospitalization hazards between LAIs, mood stabilizer plus oral antipsychotic (MS + OAP), and mood stabilizer only (MS) groups. Sensitivity analyses assessed robustness across various subgroup criteria.

LAI treatment significantly reduced the hazard of rehospitalization within one year post-discharge compared to MS + OAP (HR = 2.29, 95 % CI = 1.56-3.36) and MS alone (HR = 2.66, 95 % CI = 1.68-4.21). This effect was consistent across different rehospitalization types-all-cause, bipolar disorder-specific, and bipolar mania-specific. Each additional previous hospitalization was associated with higher hazard of rehospitalization across the three rehospitalization types. Sensitivity analyses suggested LAIs' efficacy in manic episodes with and without psychotic symptoms and for patients with frequent hospitalizations. The LAIs included in the analysis are haloperidol, risperidone, fluphenazine, flupentixol, and zuclopenthixol.

Our findings suggest that the addition of LAIs for bipolar mania during acute inpatient treatment is associated with reduced rehospitalizations, particularly among patients with recurrent hospitalizations, making it a valuable option. However, the lack of outpatient prescription data limits our ability to further substantiate this concept, warranting future research.

Bipolar disorder (BD) is a severe mental illness characterized by significant mood swings. Effective drug treatment modalities are crucial for managing BD.

To analyze the current status and future trends of global research on BD drug treatment over the last decade.

The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment. A total of 2624 articles were extracted. Data visualization and analysis were conducted using CiteSpace, VOSviewer, Pajek, Scimago Graphica, and R-studio bibliometrix to identify research hotspots, key contributors, and future trends.

The United States, China, and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration networks. The University of Pittsburgh, Massachusetts General Hospital, and the University of Michigan have been identified as the major research institutions in this field. The Journal of Affective Disorders is the most influential journal. A keyword analysis revealed research hotspots related to clinical symptoms, drug efficacy, and genetic mechanisms. A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited paper.

This study provides a detailed overview of the field of BD drug treatment, highlighting key contributors, research hotspots, and future directions. The study findings can be employed as a reference for future research and policymaking, which may enable further development and optimization of BD pharmacotherapy.

This study aimed to assess treatment patterns and the effectiveness of long-acting injectable antipsychotics (LAIs) in patients with bipolar disorder (BD) across various Asian countries. The study focused on comparing the choices of LAIs, other psychotropic medications, and their psychotropic drug load to explore real-world usage and evaluate the potential benefits of LAIs in BD treatment across different countries.

A retrospective cohort study was conducted with BD patients diagnosed according to ICD-10-CM codes F31.0 to F31.9 across 13 Asian countries or regions. Data were collected through an online system covering prescriptions for all psychotropic medications including LAIs. The Anatomical Therapeutic Chemical (ATC) Classification System was used to compare medication dosage patterns.

The study analyzed 2029 prescription records for BD, including 103 cases involving LAIs. The highest LAI prescription rates were found in Sri Lanka and Malaysia, with no reported use in Myanmar, India, and Japan. Patients receiving LAIs were younger, more often male, and had higher BMI and drug loads compared to those on oral medications. South Korea and Indonesia showed the highest LAIs drug load. South Korea, Pakistan, and China exhibited the highest total psychotropic drug loads, while Malaysia had the lowest.

This study is the first to examine LAIs use for BD across Asia. Cross-national differences in LAIs prescriptions and psychotropic drug load highlight variations in treatment practices and healthcare systems. These findings underscore the need for further research and the development of region-specific guidelines to improve BD treatment outcomes.

In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

To examine lithium use in the perinatal period.

This cohort study used individual-level data of pregnancies from January 1, 2000, to December 31, 2021, in Australia, Denmark, Finland, Germany, Hong Kong, Iceland, Israel, New Zealand, Norway, South Korea, Sweden, Taiwan, the UK, and 2 cohorts in the US. Analyses were performed from September 1 to November 30, 2023.

The prevalence of lithium use as the proportion of pregnancies with at least 1 prescription fill or prescription within 3 months before pregnancy until childbirth was estimated using a common protocol. Lithium use during pregnancy by trimester and in the 3 months before and after pregnancy was examined.

Comparison of prevalence between the first and last 3-year periods of available data.

Among 21 659 454 pregnancies from all collaborating sites, the prevalence of lithium use ranged from 0.07 per 1000 pregnancies in Hong Kong to 1.56 per 1000 in the US publicly insured population. Lithium use increased per 1000 pregnancies in 10 populations (Australia [0.60 to 0.74], Denmark [0.09 to 0.51], Finland [0.10 to 0.29], Iceland [0.24 to 0.99], Israel [0.25 to 0.37], Norway [0.24 to 0.47], South Korea [0.30 to 0.44], Sweden [0.42 to 1.07], the UK [0.07 to 0.10], and Taiwan [0.15 to 0.19]), remained stable in 4 populations (Germany [0.17 to 0.16], Hong Kong [0.06 to 0.06], and the publicly [1.50 to 1.34] and commercially [0.38 to 0.36] insured US populations), and decreased in 1 population (New Zealand [0.54 to 0.39]). Use of lithium decreased with each trimester of pregnancy, while prevalence of postpartum use was similar to prepregnancy levels. The proportion of lithium use in the second trimester compared with the prepregnancy period ranged from 2% in South Korea to 80% in Denmark.

Prevalence of lithium use in pregnant women over the past 2 decades varied markedly between populations. Patterns of use before, during, and after pregnancy suggest that many women discontinued lithium use during pregnancy and reinitiated treatment after childbirth, with large variations between countries. These findings underscore the need for internationally harmonized guidelines, specifically for psychiatric conditions among pregnant women that may benefit from lithium treatment.

The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose-response relationship for efficacy, acceptability, and metabolic/endocrine profiles.

Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose-response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs.

Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40-60 mg) improved depression (50 mg: SMD -0.60 (95% CI -0.30, -0.89)), anxiety (50 mg: -0.32 (95% CI -0.21, -0.42)), clinical global impression (50 mg: -0.67 (95% CI -0.30, -1.03)) and disability (50 mg: -0.38 (95% CI -0.08, -0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose-effect relationship. Weight increased at doses<60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses>70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)).

A daily dose of 40-60 mg of lurasidone is a reasonable choice for bipolar depression treatment.

INPLASY202430069.

Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD.

Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections.

Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5).

These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace.

PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes.

A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo.

Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Our study employs machine learning to predict serum valproic acid (VPA) concentrations, aiming to contribute to the development of non-invasive assays for therapeutic drug monitoring.

Medical records from 2002 to 2019 were obtained from the Taiwan Chang Gung Research Database. Using various machine learning algorithms, we developed predictive models to classify serum VPA concentrations into two categories (1-50 μg/ml or 51-100 μg/ml) and predicted the exact concentration value. The models were trained on 5142 samples and tested on 644 independent samples. Accuracy was the main metric used to evaluate model performance, with a tolerance of 20 μg/ml for continuous variables. Furthermore, we identified important features and developed simplified models with fewer features.

The models achieved an average accuracy of 0.80-0.86 for binary outcomes and 0.72-0.88 for continuous outcome. Ten top features associated with higher serum VPA levels included higher VPA last and daily doses, bipolar disorder or schizophrenia spectrum disorder diagnoses, elevated levels of serum albumin, calcium, and creatinine, low platelet count, low percentage of segmented white blood cells, and low red cell distribution width-coefficient of variation. The simplified models had an average accuracy of 0.82-0.86 for binary outcome and 0.70-0.86 for continuous outcome.

The study's predictive model lacked external test data from outside the hospital for validation.

Machine learning models have the potential to integrate real-world data and predict VPA concentrations, providing a promising tool for reducing the need for frequent monitoring of serum levels in clinical practice.

Non-invasive brain stimulation (NIBS) is a promising treatment for bipolar depression. We systematically searched for randomized controlled trials on NIBS for treating bipolar depression (INPLASY No: 202340019). Eighteen articles (N = 617) were eligible for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs). Anodal transcranial direct current stimulation over F3 plus cathodal transcranial direct current stimulation over F4 (a-tDCS-F3 +c-tDCS-F4; SMD = -1.18, 95%CIs = -1.66 to -0.69, N = 77), high-definition tDCS over F3 (HD-tDCS-F3; -1.17, -2.00 to -0.35, 25), high frequency deep transcranial magnetic stimulation (HF-dTMS; -0.81, -1.62 to -0.001, 25), and high frequency repetitive TMS over F3 plus low frequency repetitive TMS over F4 (HF-rTMS-F3 +LF-rTMS-F4; -0.77, -1.43 to -0.11, 38) significantly improved depressive symptoms compared to sham controls. Only a-tDCS-F3 +c-tDCS-F4 (OR = 4.53, 95%CIs = 1.51-13.65) and HF-rTMS-F3 +LF-rTMS-F4 (4.69, 1.02-21.56) showed higher response rates. No active NIBS interventions exhibited significant differences in dropout or side effect rates, compared with sham controls.