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Background: Global pharmacoepidemiological evidence suggests dynamically changing prescription patterns in patients with bipolar disorders. We assessed trends in the use of pharmacological agents used in the management of bipolar disorders in inpatients. Methods: We examined drug use data provided by the Drug Safety in Psychiatry Programme AMSP (German: "Arzneimittelsicherheit in der Psychiatrie"), including psychiatric hospitals in Germany, Austria and Switzerland. We included data from adult inpatients with bipolar disorders (ICD-10: F31) treated between 1994 and 2017. We compared prescription patterns between patients receiving therapeutic regimens with vs. without lithium. Patients with manic and depressive episodes were also analyzed separately. Results: We identified a total of 8,707 patients (58% females, mean age 50.8 ± 14.8 years). Our analysis revealed a decrease of lithium use (up to 2004) and a consistent increase of prescription rates for second-generation antipsychotics (SGA) among which quetiapine (n = 2,677) and olanzapine (n = 1,536) were the most common. Among psychotropic drugs, quetiapine was most frequently combined with lithium (n = 716, 25.6%). Lithium-treated patients received a higher number of drugs compared to patients not receiving lithium (mean number of drugs in patients with vs. without lithium 4.99, n = 2,796 vs. 4.75, n = 5,911, p = 0.002). Thyroid therapeutics were given more often, valproate and quetiapine less often in the lithium group. Antidepressants were consistently prescribed to more than 60% of patients with bipolar depressive episodes. Conclusions: Our findings suggest that SGAs are gradually becoming the mainstay treatment option in bipolar disorder, continuously replacing lithium. The use of antidepressants remains concerningly high. We call for action to improve adherence to evidence-based guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Untreated bipolar disorder in pregnancy is associated with adverse maternal and neonatal outcomes. Despite advances in clinical management, there is concern among obstetric providers and patients about the safety of pharmacological agents for the treatment of bipolar disorder in pregnancy. Recent studies have shown atypical antipsychotics and lamotrigine to have a favorable safety profile; however, little information is published on lurasidone. Objectives: The objective of this retrospective chart review was to evaluate pregnancy and neonatal outcomes in obstetric patients with bipolar disorder who are untreated, compared to those treated with lurasidone, other atypical antipsychotics, and lamotrigine at a tertiary teaching institution. Methods: This retrospective cohort study included neonates whose mothers had a diagnosis of bipolar disorder and were referred to the Maternal & Fetal Care Clinic with two documented visits after January 1, 2014, with delivery by October 31, 2017, within an SSM health‐system hospital. Results: In this study, women with untreated bipolar disorder (not on any mood stabilizer) in pregnancy had significantly higher rates of premature delivery and low birth weight compared to women on mood stabilizers of lamotrigine, lurasidone, and other atypical antipsychotics. No difference was observed for pregnancy or neonatal outcomes between patients taking any of the mood stabilizers. Conclusions: This study suggests that the use of lurasidone, other atypical antipsychotics, and lamotrigine have better neonatal outcomes than untreated bipolar disorder in pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6‐month prospective randomized‐controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE‐AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU). Methods: Inclusion criteria were AYAs age 13–21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self‐reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton Depression Rating Scale (HAM‐D) and Young Mania Rating Scale (YMRS). Results: The mean sample age (N = 36) was 19.1 years (SD = 2.0); 66.7% (N = 24) female, BD Type I (81%). The mean missed medication on TRQ for the total sample was 35.4% (SD = 28.8) at screening and 30.4% (SD = 30.5) at baseline. Both CAE‐AYA and ETAU improved on TRQ from screening to baseline. Baseline mean missed medication using SimpleMed was 51.6% (SD = 38.5). Baseline HAM‐D and YMRS means were 7.1 (SD = 4.7) and 6.0 (SD = 7.3), respectively. Attrition rate at week 24 was 36%. Baseline to 24‐week change on TRQ, adjusting for age, gender, educational level, living situation, family history, race, and ethnicity, showed improvement favoring CAE‐AYA versus ETAU of 15%. SimpleMed interpretation was limited due to substantial missing data. There was a significant reduction in depression favoring CAE‐AYA. Conclusions: CAE‐AYA may improve adherence in AYAs with BD, although conclusions need to be made cautiously given study limitations. Clinical Trials Registration: ClinicalTrials.gov identifier: NCT04348604. [ABSTRACT FROM AUTHOR]

Background: Gambling disorder (GD) is a psychiatric disorder classified in the DSM-5 as a non-substance-related and addictive disorder with extensive health and socioeconomic impacts. Its chronic and high-relapsing nature makes it essential to find treatment strategies that improve functioning and reduce impairment associated with it. The purpose of this narrative review is to evaluate and summarize the available evidence on the effectiveness and safety of pharmacotherapy in GD. Methods: An electronic literature search of Medline, Embase, and Cochrane Central was conducted to identify systematic reviews, meta-analyses, and reviews on pharmacological interventions in patients with gambling disorder. A similar search of these databases and of Prospero, Clinicaltrials.gov, and Epistemonikos was conducted to identify clinical trials that were published since 2019. Results: The initial search identified 1925 articles. After screening and duplicate removal, 18 articles were included in the review (11 studies were systematic reviews and meta-analyses, 6 were reviews, and 1 was an open-label trial). Eight pharmacological agents (naltrexone, nalmefene, paroxetine, fluvoxamine, citalopram, escitalopram, lithium, and topiramate) that were studied in randomized controlled trials and open-label trials showed small to moderate effect sizes in reducing GD symptoms in some studies during post-hoc analyses. Conclusion: The overall sum of evidence in the literature on the use of pharmacotherapy in GD is conflicting and inconclusive. Some studies have shown that pharmacotherapy's role in GD is promising, especially when the choice of the agent is guided by comorbid psychiatric disorders. However, significant limitations exist in the study designs, which need to be addressed in future research on the topic. Conducting future and more rigorous trials that address the limitations in the existing literature is necessary to establish more accurate efficacy data on the use of pharmacotherapy in this population. [ABSTRACT FROM AUTHOR]

Rationale: : Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. Objectives: To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. Methods: We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. Results: Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (β = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (β = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. Conclusions: This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients. [ABSTRACT FROM AUTHOR]

Abstract Background Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20‐year period. Methods We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran–Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20‐year period. Results Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20‐year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20‐year period. Conclusions Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic‐induced constipation.

Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically. We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk. Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies. Substantial heterogeneity among the studies precluded performing a meta-analysis. Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention. • Antipsychotic treatment response appears to differ by sex, possibly favoring women. • There is limited research on sex differences in mood stabilizer response. • Women experience more adverse effects with mood stabilizers and antipsychotics. • Hypothyroidism with lithium is more common in women. • Women using antipsychotics have more weight gain/obesity and hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Background: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20‐year period. Methods: We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran–Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20‐year period. Results: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20‐year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20‐year period. Conclusions: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic‐induced constipation. [ABSTRACT FROM AUTHOR]

Oxcarbazepine is often utilized off-label for bipolar and depressive disorders in outpatient settings despite limited evidence. We performed a retrospective chart review on 38 adult outpatients diagnosed with bipolar and depressive disorders (ICD-10 codes F30-39), treated with oxcarbazepine by psychiatrists and psychiatric nurse practitioners between 2015 and 2021. Primary outcomes were Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores, assigned retrospectively from clinical documentation. Patients were predominantly female (70%), aged 20–76 (mean 36), with a mean of 1.8 DSM diagnoses (range 1–4) and 1.7 (range 0–5) concurrent psychotropic medications. A starting mean oxcarbazepine dose of 489 mg/day, titrated to a mean final dose of 663 mg/day, was associated with a CGI-I of 2.5 [2.25, 2.75] and a pre-to-post treatment decrease in CGI-S from 3.4 to 2.4. Overall response and remission rates were 52% and 29%, respectively. Limitations of this study include potential sample bias, documentation bias and rater bias among other limitations inherent to retrospective study designs.

Psychiatric illness may develop or relapse during pregnancy, and understanding best practices is paramount. In 2017, the British Association for Psychopharmacology (BAP) consensus guidance on the use of psychotropic medication preconception, in pregnancy, and postpartum was released. The BAP guidelines provide concise evidence and additional insight and flexibility for use of psychiatric medication. Key takeaways of these guidelines are highlighted serving as a concise reference for practitioners. Additionally, practice points, such as recommendations for rapid tranquilization and the role of long-acting injectable antipsychotic medications as well as additional insights to the growing body of literature associated with psychiatric medications in pregnancy since 2017 are summarized. Providers are strongly encouraged to stay up to date to provide optimal care for pregnant patients and their babies.

Abstract Background The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). Methods We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: “Arzneimittelsicherheit in der Psychiatrie”; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. Results We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9–5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7–28.3, p

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: Anxiety disorder is present in approximately half of all bipolar disorder (BD) patients. There are neurologic bases for the comorbidity of balance (vestibular) disorders and anxiety. Our objective is to use electrovestibulography (EVestG), which is predominantly a measure of vestibular neural activity to not only quantitatively detect and measure comorbid anxiety disorder but also to quantitatively measure the impacts of anti-depressant, anti-psychotic, and mood stabilizer medication groups on anxiety measures in BD patients. Methods: In a population of 50 (24 with anxiety disorder) depressive phase BD patients, EVestG signals were measured. Participants were labeled depression-wise as anxious or non-anxious using standard questionnaires. Analyses were conducted on the whole dataset as well as on matched (age/gender/MADRS) and “modeled medication-free” subsets. Modulations of the low-frequency EVestG firing pattern data were measured. Findings: For BD, the main anxious minus non-anxious dierence was the presence of an increase in spectral power proximal to 8–9 Hz, which was best attenuated by mood stabilizers. Novelty: This is the first study to use an oto-acoustic physiological measure to quantify anxiety disorder in BD wherein it appears to manifest as a peak proximal to 8–9 Hz which we hypothesize as likely linked to hippocampal theta. [ABSTRACT FROM AUTHOR]

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O'Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use. [ABSTRACT FROM AUTHOR]

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS. [ABSTRACT FROM AUTHOR]

Background: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. Objective: Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. Methods: To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. Results: Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. Conclusions: This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. International Registered Report Identifier (IRRID): DERR1-10.2196/64446 [ABSTRACT FROM AUTHOR]

Background: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. Methods: We enrolled patients with schizophrenia attending each hospital (n=14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran- Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. Results: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated magnesium oxide, lubiprostone and elobixibat were differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. Conclusions: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation. [ABSTRACT FROM AUTHOR]

Background: Weight gain is a side effect of antipsychotic medications, and improved management remains an unmet need in the field (James Lind Alliance, 2011). Prevention and early intervention of antipsychotic-induced weight gain (AIWG) require an accurate prediction of its incidence. To predict AIWG incidence in clinical settings, assessing the effect of factors such as type, daily dose, and the number of antipsychotics is crucial, as well as concomitant medication type and background factors in naturalistic studies that consider facility characteristics. However, no studies have been conducted to predict its occurrence based on these assessments. Aims and Objectives: This study aimed to identify the predictors of AIWG incidence by examining the effects of backgroundand medication-related factors on weight gain in patients with schizophrenia and bipolar disorder newly initiated on antipsychotic medication. Methods: This was a nationwide, multicenter (24 general hospitals, 17 psychiatric hospitals, and 3 psychiatric clinics) prospective cohort study conducted in Japan. We recruited patients with schizophrenia, schizoaffective disorder, and bipolar disorder who were newly initiated on antipsychotic treatment. The primary endpoint was AIWG incidence (weight gain of 7% or greater) within the first 12 months after the initiation of antipsychotic treatment. We sought to identify the predictors of AIWG incidence in a multivariate analysis adjusting for background (including coexisting diagnoses, diet and exercise therapies, smoking and drinking habits, and duration of illness) and medication-related factors (type, daily dose, number of antipsychotic medication, and type of concomitant medication). We employed the Cox proportional hazards regression model, stratified by facility characteristics (university hospital, general hospitals, psychiatric hospitals, and psychiatric clinics). Results: Among the 865 patients, 262 patients (30.3%) developed AIWG. Concerning medication-related factors, compared with the initiation of treatment with aripiprazole, the initiation of treatment with clozapine and olanzapine has a significantly higher AIWG incidence (hazard ratio [HR] = 2.17, 95% CI = 1.05- 4.51; HR = 2.01, 95% CI = 1.36-2.96, respectively). Conversely, the initiation of treatment with blonanserin significantly decreased AIWG incidence (HR = 0.49, 95% CI = 0.24-0.98). In terms of antidepressants, the combination of trazodone (HR = 2.53, 95% CI = 1.17-5.50), selective serotonin reuptake inhibitor (HR = 2.30, 95% CI = 1.46-3.64), and mirtazapine (HR = 1.86, 95% CI = 1.04-3.34) significantly increased AIWG incidence. Regarding mood stabilizers, the combination of lithium carbonate and valproic acid (HR = 1.60, 95% CI = 1.01-2.53; HR = 1.53, 95% CI = 1.04-2.23, respectively) significantly increased AIWG incidence. Concerning background factors, outpatients and those receiving their first treatment had a higher AIWG incidence (HR = 1.75, 95% CI = 1.27-2.41; HR = 2.04, 95% CI = 1.38-3.02, respectively). Discussion And Conclusion: The results of this study suggest that predicting AIWG incidence requires consideration not only of the type of newly initiated antipsychotic medication but also the type of concomitant medications (antidepressants and mood stabilizers) and patient treatment status. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder show higher suicide rate and mortality rate of suicidal behavior than the general population. Although several studies have revealed that lithium and some mood stabilizers might prevent suicide in bipolar disorder, it is difficult to clearly confirm the treatment effect on suicide due to the relatively short study period and low suicide rate. Aims & Objectives: This study is aimed to examine and compare the long-term effects of mood stabilizers such as lithium and valproate and atypical antipsychotics on suicide attempt and suicide (hereinafter referred to as suicide incidents) in a large cohort of bipolar patients in Korea. Method: This retrospective cohort study drawn from Korean national health insurance claims database included 44,694 individuals aged 15-50 years who had at least two main diagnoses of bipolar disorder and at least two prescriptions for lithium, valproate, carbamazepine or atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole) within one year of a diagnosis between January 1, 2002 and December 31, 2020. We examined the hazard ratios of suicide attempts, identified by an emergency room diagnosis, and suicide, confirmed by linking the cause of death data, during treatment periods with each drug by using Cox proportional regression. Suicide incidents were repeatedly measured by using between-individual and withinindividual analyses. Medication was regarded as a time-dependent variable, contributing to the estimation of suicide-related risk of each medication when changed. Results: When exposure periods by each medication were considered, the lowest rate of suicide incidents occurred when lithium alone was prescribed, followed by lithium plus valproate and valproate alone. The risk of suicide incidents was significantly reduced by 39.2% and 26.0%, respectively during treatment with lithium alone and valproate alone compared to the period without lithium, valproate or atypical antipsychotics treatment after adjustment for age, sex, income status, past history of suicide attempts, comorbid medical and psychiatric diseases, and concurrent other psychotropic medications in between- individual analysis. In withinindividual analysis controlling for time-invariant confounders, the risk of suicide incidents was most significantly reduced during the combination of lithium and atypical antipsychotics by 0.154 times. When lithium, valproate, and atypical antipsychotics were combined, the risk was significantly reduced by 0.235 times compared to the period without lithium, valproate or atypical antipsychotics treatment. Valproate showed 0.251-fold decrease in the risk of suicide incidents, and there was 0.302-fold decrease in combination therapy with atypical antipsychotics. Discussion & Conclusion: In patients with bipolar disorder, risk of suicide incidents is reduced during the treatment period with lithium alone and valproate alone compared to the period when none of lithium, valproate, or atypical antipsychotics was prescribed. In subjects with suicide incidents, atypical antipsychotics might have protective effect against suicide incidents when combined with lithium and valproate. [ABSTRACT FROM AUTHOR]

Pharmacotherapy remains crucial for treating bipolar disorder (BD), but knowledge on the treatments actually used by newly diagnosed patients in real-world settings is sparse. Individuals newly diagnosed with BD during 1996–2018, aged 15–65 years, were identified from national Finnish registers. The patients' use of different drug classes (mood stabilizers, antipsychotics and antidepressants) or combinations of these drug classes were followed from initial pharmacotherapy (first line) after BD diagnosis until the fifth line of treatment or until the two-year follow-up time ended. Clinical and sociodemographic factors associated with antidepressants-only as the first treatment line were assessed with logistic regression. 82.6 % of all patients used BD medication during the follow-up. 33.9 % had antidepressants-only as the first, 22.9 % as the second and 19.7 % as the third treatment line. Use of combinations of mood stabilizers, antipsychotics and antidepressants increased by successive treatment lines. Factors associated with antidepressants-only as the first treatment line included older age (>45 years aOR 2.20, 95% CI: 2.01–2.40, 25–45 years: 1.55, 1.42–1.68, compared with those aged <25), diabetes (1.35, 1.17–1.55) and female sex (1.29, 1.21–1.37). BD diagnosis registered in 2016–2018 (0.48, 0.42–0.55) and substance abuse (0.77, 0.71–0.83) were associated with decreased odds. Due to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. A large proportion of patients with bipolar disorder are not treated according to treatment guidelines, as use of antidepressants alone is common. Reasons for not following evidence-based recommendations need to be further researched. • Despite clinical guidelines, use of antidepressants alone was frequent among persons with incident BD. • Older age, female sex and comorbid diabetes were associated with antidepressant use. • Use of mood stabilizers, such as lithium was observed to be remarkably low. • Findings support the need for increasing the use of evidence-based treatments for BD. [ABSTRACT FROM AUTHOR]

Background: The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). Methods: We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. Results: We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9–5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7–28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3–8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1–5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. Conclusions: Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives. [ABSTRACT FROM AUTHOR]

Schizophrenia is a known risk factor for coronavirus disease (COVID-19) infection and severity, and certain psychotropic drugs have been linked to increased mortality in infected patients with schizophrenia. However, little evidence exists regarding this risk. We retrospectively examined the association between mood stabilizers and the risk of pneumonia in patients with schizophrenia. This study included 99 patients with schizophrenia or schizoaffective disorder who were infected with COVID-19 in 2022 and met the inclusion criteria. After conducting propensity score matching to align patient backgrounds and concomitant medications, we assessed the impact of mood stabilizers, specifically sodium valproate, on the risk of pneumonia development. Univariate analysis revealed that patients with schizophrenia and COVID-19 who developed pneumonia were more likely to be older (64.5 [14.2] vs. 57.4 [11.5] years, p = 0.008) and using sodium valproate (44.4% vs. 16.7%, p = 0.004). Even after propensity score matching, patients who developed pneumonia were still more likely to be receiving sodium valproate than not (58.8% vs. 20.0%, p = 0.003). Sodium valproate use may be a risk factor for the development of pneumonia in patients with chronic schizophrenia who are infected with COVID-19 during long-term hospitalization. [ABSTRACT FROM AUTHOR]

Background: Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia. Methods: We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted. Results: A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)]. Conclusions: The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What proportion of adults aged 50 years or older living in the community are using lithium? • What is the main finding of this study? The proportion of older adults dispensed lithium decreases with age, from 0.4% for those aged 50–59 years to < 0.1% for those aged ≥ 90 years. Most older adults dispensed lithium were dispensed other medications, such as antipsychotics, antidepressants, anxiolytics/hypnotics, and medications to treat diseases of the alimentary, cardiovascular, endocrine and nervous systems. • What is the meaning of the finding? The proportion of older adults dispensed treatment with lithium is lower than the known prevalence of older adults with bipolar disorder, suggesting that lithium is under-utilized in this population. Lithium use seems to be declining in clinical practice. We examined the proportion of adults aged ≥ 50 years dispensed lithium between 2012 and 2021, and investigated the proportion of lithium users dispensed other medications. We used a 10% random sample data of the Australian Pharmaceutical Benefits Scheme from 2012 to 2021, and limited our analyses to adults aged ≥ 50 years. We retrieved data on lithium, other mood stabilisers, antipsychotics, antidepressants, anxiolytics and hypnotics, and medications for the treatment of other health systems. We received 7081939 person-years records (53.2% women). The proportion of participants dispensed lithium decreased with age: 0.4% for those aged 50-59 years to < 0.1% for people aged ≥ 90 years. The dispensing of lithium increased over 10 years for those aged 50-69 and decreased in those older than 80 years. Among people dispensed lithium, nearly 1 in 5 were dispensed another mood stabiliser. Antipsychotics and antidepressants were dispensed to about 60% of participants dispensed lithium, with antidepressants dispensed more frequently to women than men. About 20% of people dispensed lithium were dispensed anxiolytics/hypnotics, more frequently for women than men. Medications to treat diseases of the alimentary, cardiovascular, endocrine and nervous systems were commonly dispensed to those dispensed lithium, as were antibiotics. While the dispensing of lithium increased among young older adults since 2015 when guidelines for the management of mood disorders were published, our findings suggest that lithium may be under-utilised for the management of bipolar disorder in later life. [ABSTRACT FROM AUTHOR]

Abstract Background Childbearing-aged female patients and elderly patients with bipolar disorder need special attention for pharmacological treatments, but current guidelines provide little information on their pharmacological treatment. In particular, the risk/benefit balance of pharmacological treatment for childbearing-aged females with bipolar disorder is a growing concern. Therefore, we aimed to address the effect of age and sex on psychotropic drug prescription for outpatients with bipolar disorder. Methods The MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study was conducted, and data on age, sex, and details of pharmacological treatment were collected. Results A total of 3106 outpatients were included in this study. Among young females (age ≤ 39), 25% were prescribed valproate. There was no significant difference in the frequency and daily dose of valproate prescription for young females among all groups. Valproate prescriptions were significantly less frequent among young males and more frequent among middle-aged males. Lithium prescriptions were significantly less frequent among young females and more frequent among older males (age ≥ 65) and older females. Lamotrigine prescriptions were significantly more frequent among young males and young females and less frequent among older males and older females. Carbamazepine prescriptions were significantly less frequent among young males and more frequent among older males. Conclusions Biased information about the risk and safety of valproate and lithium for young females was suggested, and further study to correct this bias is needed. Older patients were prescribed lithium more commonly than lamotrigine. Further studies are needed to determine the actual pharmacotherapy for elderly individuals.

Objective: In patients with bipolar disorder (BD), rapid cycling (RC) presents a risk for a more severe illness, while euthymia (EUT) has a better prognosis. This study focused on the progression of RC and EUT, which are contrasting phenomenology, and aimed to clarify the influence of patient backgrounds and prescription patterns on these different progressions, using a large sample from the first and second iterations of a multicenter treatment survey for BD in psychiatric clinics (MUSUBI). Methods: In the cross-sectional study (MUSUBI), a questionnaire based on a retrospective medical record survey of consecutive BD cases (N = 2,650) was distributed. The first survey was conducted in 2016, and the second one in 2017. The questionnaire collected information on patient backgrounds, current episodes, and clinical and prescribing characteristics. Results: In the first survey, 10.6% of the participants had RC and 3.6% had RC for two consecutive years, which correlated with BP I (Bipolar disorder type I), suicidal ideation, duration of illness, and the use of lithium carbonate and antipsychotic medications. Possible risk factors for switching to RC were comorbid developmental disorders and the prescription of anxiolytics and sleep medication. Moreover, 16.4% of the participants presented EUT in the first survey, and 11.0% presented EUT for two consecutive years. Possible factors for achieving EUT included older age; employment; fewer psychotic symptoms and comorbid personality disorders; fewer antidepressants, antipsychotics, and anxiolytics, and more lithium prescriptions. Conclusion: RC and EUT generally exhibit conflicting characteristics, and the conflicting social backgrounds and factors contributing to their outcomes were distinctive. Understanding these clinical characteristics may be helpful in clinical practice for management of patients with BD. [ABSTRACT FROM AUTHOR]

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown. Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients. Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of colinearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias. Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP. Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients. [ABSTRACT FROM AUTHOR]

Introduction: The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019. Methods: PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second‐ and first‐generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran‐Armitage Trend test. Results: The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased. Discussions: Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required. [ABSTRACT FROM AUTHOR]

Objectives: People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all‐cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. Methods: In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time‐dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. Results: The SMRs of all‐cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all‐cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5‐year follow‐up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all‐cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). Conclusion: In addition to having protective effects against suicide and all‐cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality. [ABSTRACT FROM AUTHOR]

Lithium, divalproex, and oxcarbazepine are commonly prescribed medications used for the management of bipolar disorder, but each of these drugs comes with its own gamut of adverse effects that make these agents unfavorable in certain medical conditions. Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, originally used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes in bipolar disorder. This case report highlights the use of endoxifen in the management of severe manic symptoms of bipolar disorder in a 65-year-old male patient with medical comorbidities arising from traditional mood stabilizer drugs and its potential as an alternative treatment over such drugs., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Dr. Nikhil Gautam declare(s) Support for attending meetings from Intas Pharmaceuticals Ltd. Support for attending meetings and drug samples for patients at a discounted price were provided by the company. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Gautam et al.)

Pregnancy in women with bipolar disorder (BD) can be considered a high-risk pregnancy in view of several clinical and pharmacotherapeutic considerations. Pharmacological treatment during pregnancy requires a careful weighing of psychotropic drug exposure against the risk of BD relapse. An untreated bipolar illness can negatively affect the health of mother as well as unborn child in the event of a relapse. Availability of well balanced, latest information on safety of prophylactic drugs for BD is crucial for making informed decisions. The review provides an evidence-based update (2015–2021) on the drug safety considerations involved in providing care for women with BD who are either pregnant or planning to conceive in near future. Literature review based on systematic reviews, meta-analyses, and data available from studies based on large-scale cohorts and birth registries has been synthesized and presented along with clinically relevant recommendations. [ABSTRACT FROM AUTHOR]

Lithium treatment is considered the gold standard for the long-term management of bipolar disorder and recurrent unipolar depression. It is also extremely effective in other psychiatric conditions characterized by impulsivity and aggression, and for the prevention of suicidal behaviours. This paper provides a scoping review and an expert commentary regarding the use of lithium in adult patients. Available information about efficacy, tolerability, dosing, and switching is analyzed, and the strategies that may be most useful in real-world clinical settings are highlighted. Lithium is effective on different domains of bipolar disorder, including the long-term prevention of recurrences of affective episodes, management of acute mania as well as in the prophylaxis of all affective episodes. Lithium has been defined a 'forgotten drug,' since its use in routine clinical practice has been declined over the last 20 or 30 years. Reasons for this trend include lack of adequate training on the management of lithium side effects. Considering its efficacy, use of lithium in ordinary clinical practice should be promoted. Several strategies, such as using slow-release formulations, can be easily implemented in order to minimize lithium side effects and improve its tolerability profile. [ABSTRACT FROM AUTHOR]

Background: Childbearing-aged female patients and elderly patients with bipolar disorder need special attention for pharmacological treatments, but current guidelines provide little information on their pharmacological treatment. In particular, the risk/benefit balance of pharmacological treatment for childbearing-aged females with bipolar disorder is a growing concern. Therefore, we aimed to address the effect of age and sex on psychotropic drug prescription for outpatients with bipolar disorder. Methods: The MUlticenter treatment SUrvey for BIpolar disorder in Japanese psychiatric clinics (MUSUBI) study was conducted, and data on age, sex, and details of pharmacological treatment were collected. Results: A total of 3106 outpatients were included in this study. Among young females (age ≤ 39), 25% were prescribed valproate. There was no significant difference in the frequency and daily dose of valproate prescription for young females among all groups. Valproate prescriptions were significantly less frequent among young males and more frequent among middle-aged males. Lithium prescriptions were significantly less frequent among young females and more frequent among older males (age ≥ 65) and older females. Lamotrigine prescriptions were significantly more frequent among young males and young females and less frequent among older males and older females. Carbamazepine prescriptions were significantly less frequent among young males and more frequent among older males. Conclusions: Biased information about the risk and safety of valproate and lithium for young females was suggested, and further study to correct this bias is needed. Older patients were prescribed lithium more commonly than lamotrigine. Further studies are needed to determine the actual pharmacotherapy for elderly individuals. [ABSTRACT FROM AUTHOR]

BackgroundBipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response.Methods/designThis study is an 11-site prospective non-randomized open trial of lithium designed to ascertain a cohort of 700 subjects with bipolar I disorder who experience protocol-defined relapse prevention as a result of treatment with lithium monotherapy. All patients will be diagnosed using the Diagnostic Interview for Genetic Studies (DIGS) and will then enter a 2-year follow-up period on lithium monotherapy if and when they exhibit a score of 1 (normal, not ill), 2 (minimally ill) or 3 (mildly ill) on the Clinical Global Impressions of Severity Scale for Bipolar Disorder (CGI-S-BP Overall Bipolar Illness) for 4 of the 5 preceding weeks. Lithium will be titrated as clinically appropriate, not to exceed serum levels of 1.2 mEq/L. The sample will be evaluated longitudinally using a wide range of clinical scales, cognitive assessments and laboratory tests. On relapse, patients will be discontinued or crossed-over to treatment with valproic acid (VPA) or treatment as usual (TAU). Relapse is defined as a DSM-IV manic, major depressive or mixed episode or if the treating physician decides a change in medication is clinically necessary. The sample will be genotyped for GWAS. The outcome for lithium response will be analyzed as a time to event, where the event is defined as clinical relapse, using a Cox Proportional Hazards model. Positive single nucleotide polymorphisms (SNPs) from past genetic retrospective studies of lithium response, the Consortium on Lithium Genetics (ConLiGen), will be tested in this prospective study sample; a meta-analysis of these samples will then be performed. Finally, neurons will be derived from pluripotent stem cells from lithium responders and non-responders and tested in vivo for response to lithium by gene expression studies. SNPs in genes identified in these cellular studies will also be tested for association to response.DiscussionLithium is an extraordinarily important therapeutic drug in the clinical management of patients suffering from bipolar disorder. However, a significant proportion of patients, 30-40 %, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment. Converging evidence suggests that genetic factors play a strong role in the variation of response to lithium, but only a few genes have been tested and the samples have largely been retrospective or quite small. The current study will collect an entirely unique sample of 700 patients with bipolar disorder to be stabilized on lithium monotherapy and followed for up to 2 years. This study will produce useful information to improve the understanding of the mechanism of action of lithium and will add to the development of a method to predict individual response to lithium, thereby accelerating recovery and reducing suffering and cost.Trial registrationClinicalTrials.gov Identifier: NCT01272531 Registered: January 6, 2011.

Objective: Medical treatments for patients with refractory schizophrenia can be roughly divided into three strategies – clozapine administration, adjuvant use of mood stabilizers, and antipsychotic polypharmacy. Few studies exist on older adult patients with schizophrenia. In this study, we intended to assess the prevalence of clozapine administration, adjuvant use of mood stabilizers, and antipsychotic polypharmacy, and to find their predictors in those patients with schizophrenia. Methods: In this cross-sectional study, we collected information of patients' sociodemographic and clinical details. Their psychotic symptoms were evaluated using a clinical interview with a positive and negative syndrome scale (PANSS). Results: We enrolled 240 study participants, with 74 patients (30.8%) receiving clozapine, 40 patients (16.7%) receiving adjuvant use of mood stabilizers, and 42 patients (17.5%) receiving antipsychotic polypharmacy. Younger age (p < 0.05), higher PANSS general symptoms subscales (p < 0.001), and higher dosage of antipsychotics (p < 0.01) were significantly related to patients with clozapine administration. As to patients with adjuvant therapy with mood stabilizers, only younger age (p < 0.01) and male gender (p < 0.05) showed significant association. Finally, patients receiving antipsychotic polypharmacy were significantly related to lower body mass index (BMI) (p < 0.05), higher PANSS positive symptoms subscale (p < 0.05), and higher dosage of antipsychotics (p < 0.001). Conclusions: Our findings showed that patients with clozapine prescription were 30.8% in prevalence which is higher than other studies in Asia. The prevalence of adjuvant mood stabilizers and antipsychotic polypharmacy were 16.7% and 17.5%, respectively. Those two findings are lower than those in other studies in Asia.

Objective: Medications for the treatment of bipolar disorder (BD) could affect patients' cognitive function. Patients with BD present with neurocognitive impairment even in a remission state. Little research is available on the daily functioning, especially driving performance, of stable outpatients with BD under pharmacological treatment. Methods: In total, 58 euthymic outpatients with BD undergoing real‐world pharmacotherapy and 80 sex‐ and age‐matched healthy controls (HCs) were enrolled. Three driving tasks using a driving simulator—road‐tracking, car‐following, and harsh‐braking—and three cognitive tasks—Continuous Performance Test, Wisconsin Card Sorting Test, and Trail‐Making Test—were evaluated. Symptom assessment scales—Young Mania Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory‐II, Social Adaptation Self‐evaluation Scale, and Stanford Sleepiness Scale—were also completed. Results: Car‐following and road‐tracking performance were significantly impaired in patients with BD compared with HCs after adjusting for demographic variables, but these performances generally overlapped. Broad neurocognitive functions were significantly lower in the patients with BD compared to HCs, but car‐following performance was significantly negatively correlated with sustained attention only. Although most patients received multiple medications rather than monotherapy, no relationship between prescriptions and driving performance was found. Conclusion: Euthymic patients with BD under steady‐state pharmacotherapy had impaired driving performance compared with HCs, but the overlapping distributions of driving performance suggested that driving performance is not always deteriorated in patients with BD. Therefore, attentional function may be a useful clinical feature for judging driving aptitude in patients with BD. [ABSTRACT FROM AUTHOR]

Aims: Patients with brain diseases have been associated with several retinal abnormalities. This study aimed to assess the risk of retinal diseases in patients with bipolar disorder (BD). Methods: This nationwide cohort of 73,271 patients with BD was enrolled between 2001 and 2009. To identify newly diagnosed retinal diseases, the patients were followed to the end of 2011. The control group included 293,084 patients, matched for demographic characteristics and medical and ophthalmological comorbidities. The Kaplan–Meier method was used to estimate incidence rates of retinal diseases. Cox regression was applied to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs) after adjusting for confounders. Results: Patients with BD had higher incidence rates of any retinal disease than the controls (1.27% vs 0.48%, P < 0.001), and retinal diseases were diagnosed at a young age (54.23 years [±12.68 years] vs 57.01 years [±13.12 years], P < 0.001). After adjusting for demographic characteristics, physical and ophthalmological comorbidities, and medications, the HR was 3.24 (95% CI, 2.18–4.82) for retinal detachment, 2.35 (95% CI, 1.83–3.03) for primary retinopathy, 2.26 (95% CI, 1.91–2.68) for diabetes retinopathy, 2.39 (95% CI, 1.49–3.82) for hypertensive retinopathy, and 3.46 (95% CI, 2.45–4.89) for retinal vascular complications in patients with BD vs controls. The cumulative daily dose of bipolar medications was not associated with the incidence of any retinal disease. Conclusion: Patients with BD were associated with a higher risk of retinal detachment, primary retinopathy, diabetes retinopathy, hypertensive retinopathy, and retinal vascular complications than the controls. Further studies are needed to examine the mechanisms mediating these retinal diseases in patients with BD. [ABSTRACT FROM AUTHOR]

Takashi Tsuboi,1,2 Takefumi Suzuki,2,3 Takaharu Azekawa,4 Naoto Adachi,4 Hitoshi Ueda,4 Kouji Edagawa,4 Eiichi Katsumoto,4 Yukihisa Kubota,4 Eiichiro Goto,4 Seiji Hongo,4 Yoichiro Watanabe,4 Masaki Kato,2,5 Norio Yasui-Furukori,2,6 Reiji Yoshimura,2,7 Atsuo Nakagawa,2,8 Toshiaki Kikuchi,2,8 Koichiro Watanabe1,2 1Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 2The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan; 3Department of Neuropsychiatry, University of Yamanashi Faculty of Medicine, Yamanashi, Japan; 4The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan; 5Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 6Department of Psychiatry, Dokkyo Medical University, Tochigi, Japan; 7Department of Psychiatry, University of Occupational and Environmental Health, Fukuoka, Japan; 8Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanCorrespondence: Takashi TsuboiDepartment of Neuropsychiatry, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-Shi, Tokyo 181-8611, JapanTel +81 422 47 5511Fax +81 422 45 4697Email takashi.tsuboi.0821@gmail.comPurpose: The aim of this study was to identify factors associated with non-remission in bipolar disorder.Patients and Methods: The multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics (MUSUBI) study used a questionnaire administered at 176 clinics throughout Japan from September to October 2016. Clinic psychiatrists performed a retrospective medical record survey of consecutive cases with bipolar disorder. Patients were considered to be in remission if they met all of the following criteria: they were not in a mixed state, their manic or depressive symptoms were either borderline or nonexistent (corresponding to 2 or 1 points on the Clinical Global Impressions Scale, Bipolar Version), and their psychiatrists clinically considered them to be in remission. Enrolled patients were classified into remitters group and non-remitters group and demographic and clinical characteristics were contrasted between the groups. Non-remitters were compared with remitters, using a series of logistic regression analyses.Results: A total of 3130 patients (1420 men; mean age: 50.3 years) were included in this study; 1307 patients (41.8%) were in remission. Of the remaining 1823 patients, 1260 (40.3%) had mild to severe depression, 261 (8.3%) suffered from manic or hypomanic episodes, and 302 (9.6%) were in a mixed state. Logistic regression analyses found the following eight factors to be significantly correlated with non-remission in patients with bipolar disorder: female gender, younger age, unemployed status, rapid cycling pattern, comorbid alcohol/substance abuse, poorer social function, lithium non-use, and antidepressant use.Conclusion: The MUSUBI study, the largest nationwide investigation on bipolar disorder, identified eight clinically relevant factors associated with non-remission in bipolar patients. They have important clinical implications; further prospective studies are necessary to replicate these findings and to guide better managements for those in serious needs.Keywords: bipolar disorder, non-remission, nationwide study, mood stabilizer, antipsychotics

Lithium and mood stabilizers are considered effective augmentation agents of antidepressants for treatment-resistant depression. Thus, this study aimed to estimate the network structure of depression symptom criteria among unipolar depression patients with mood stabilizers, using data from the Research on Asian Psychotropic Prescription Patterns for mood stabilizers (REAP-MS). We estimated a network of the 9 depression symptom criteria among 411 unipolar depression patients in Asia. Each of the depression symptom criteria was considered to be a dichotomous categorical variable. Suicidality (suicidal ideation or attempt) was the most centrally situated within the network of depression symptoms, followed by depressed mood, loss of energy, anhedonia and weight loss or gain. Contrastingly, concentration problem was the least interconnected. The depression symptom criteria were organized into 4 clusters by the community detection method. The findings suggest that suicidality may be one of the significant therapeutic target symptoms in unipolar depression patients with mood stabilizers., Competing Interests: Declaration of Competing Interest Seon-Cheol Park, an editorial board member of the Asian Journal of Psychiatry, was not involved in the evaluation of or decision to publish this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This case study explores the management of a 22-year-old male patient diagnosed with recurrent refractory catatonia, a neuropsychiatric condition characterized by motor, behavioral, and autonomic disturbances often associated with bipolar disorder. Despite comprehensive investigations, including normal results in tests such as complete blood count (CBC), liver function tests (LFT), thyroid function tests (TFT), renal function tests (RFT), C-reactive protein (CRP), creatine kinase (CKP), and serum electrolytes, the patient's condition persisted. Initial treatments with conventional therapies, such as benzodiazepines, proved unsuccessful. However, the introduction of cariprazine, an atypical antipsychotic, combined with electroconvulsive therapy (ECT), resulted in significant improvement. This case highlights the challenges of managing treatment-resistant catatonia and suggests cariprazine's potential role in preventing catatonic relapses when other therapies fail. The patient's sustained remission underscores the need for further investigation into cariprazine as a viable option for refractory cases., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Qasab et al.)