Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.

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 (ß = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (ß = 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.

Who is at risk for weight gain after weight-gain associated treatment with antipsychotics, antidepressants, and mood stabilizers: A machine learning approach.

BACKGROUND: Weight gain is a common side effect in psychopharmacology; however, targeted therapeutic interventions and prevention strategies are currently absent in day-to-day clinical practice. To promote the development of such strategies, the identification of factors indicative of patients at risk is essential. METHODS: In this study, we developed a transdiagnostic model using and comparing decision tree classifiers, logistic regression, XGboost, and a support vector machine to predict weight gain of ≥5% of body weight during the first 4 weeks of treatment with psychotropic drugs associated with weight gain in 103 psychiatric inpatients. We included established variables from the literature as well as an extended set with additional clinical variables and questionnaires. RESULTS: Baseline BMI, premorbid BMI, and age are known risk factors and were confirmed by our models. Additionally, waist circumference has emerged as a new and significant risk factor. Eating behavior next to blood glucose were found as additional potential predictor that may underlie therapeutic interventions and could be used for preventive strategies in a cohort at risk for psychotropics induced weight gain (PIWG). CONCLUSION: Our models validate existing findings and further uncover previously unknown modifiable factors, such as eating behavior and blood glucose, which can be used as targets for preventive strategies. These findings underscore the imperative for continued research in this domain to establish effective preventive measures for individuals undergoing psychotropic drug treatments.

Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: A systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Substantial heterogeneity among the studies precluded performing a meta-analysis. CONCLUSION: 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.

International Trends in Lithium Use for Pharmacotherapy and Clinical Correlates in Bipolar Disorder: A Scoping Review.

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.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

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.

Patterns of pharmacotherapy for bipolar disorder: A GBC survey.

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.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

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.

Concepts for selection and utilization of psychiatric medications in pregnancy.

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.

Significant Weight Gain With the Administration of Lurasidone and Valproic Acid in Schizophrenia and Bipolar Disorder Patients.

Antipsychotics are frequently used to treat psychiatric disorders and have been associated with weight gain. Mental disorders are likely to reduce patients' quality of life. Unhealthy lifestyles such as reduced physical activity, sleep disturbances, and irregular diets can lead to weight gain. Herein, we report two cases of schizophrenia and bipolar disorder who had a 10-kg gain in weight in six months with the administration of lurasidone and valproic acid. Lurasidone has fewer side effects, such as weight gain and somnolence. However, concomitant use of sedating antipsychotics or mood stabilizers in the acute phase and multiple doses increase the risk of weight gain. Additionally, various factors, including psychiatric symptoms and lifestyle changes, are believed to contribute to weight gain, and a comprehensive approach should be followed.

Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data.

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.

Sodium Valproate Use in Japanese Patients with Schizophrenia and Coronavirus Disease Is Associated with an Increased Risk of Pneumonia.

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.

Real-world use of pharmacological treatments for incident bipolar disorder: A Finnish nationwide cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Due to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. CONCLUSIONS: 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.

Pharmacotherapy and gambling disorder: a narrative review.

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.

Clinical characteristics and prescriptions associated with a 2-year course of rapid cycling and euthymia in bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric clinics.

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.

Chronic Mania: Diagnostic Dilemma and the Need for Addition in Nosology.

Chronic mania is a mental health disorder that has been described by various psychiatrists in the past but currently is not a part of nosology. Robust epidemiological data for chronic mania are lacking with regard to its prevalence and clinical features. The present case report is of a 48-year-old male with a six-year history of mood and psychotic symptoms, based on which differential diagnoses of schizoaffective disorder (manic type), schizophrenia, and mania with psychotic symptoms (with chronic course) were made. The diagnosis of chronic mania was confirmed considering the predominance of fluctuating mood symptoms along with psychotic symptoms, lack of remission, and chronic course of illness. Antipsychotics were initially started for six weeks, to which the patient demonstrated a minimal response. A mood stabilizer was added to the regimen, leading to significant improvement, and the patient was discharged. According to existing literature, patients with chronic mania present with severe illness, the presence of psychotic symptoms, and socio-occupational impairment, which was also noticed in this case. The prevalence of chronic mania among patients with bipolar disorder is approximately 13-15%, which constitutes a significant proportion of known mental illnesses. Therefore, chronic mania should be added as a distinct clinical entity in the existing nosological systems.

Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study.

OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar. METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection. RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication. CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

An Unusual Cause of Persistent Tachycardia: Atypical Neuroleptic Malignant Syndrome.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening emergency caused more commonly by typical antipsychotics. However, unusual presentations of NMS are intermittently reported with the use of atypical antipsychotics. We present the case of a 42-year-old gentleman with schizoaffective and bipolar disorder who was admitted for change in mentation and lithium toxicity. His mentation did not improve despite being dialyzed and the resolution of lithium level to baseline. He developed persistent tachycardia and hyperthermia, initially attributed to Streptococcal infection. But despite appropriate antibiotic therapy, his clinical symptoms did not improve. An extensive workup for his neurological symptoms, including lumbar puncture, 5-hydroxy indole acetic acid urine test, and brain magnetic resonance imaging, was inconclusive of any underlying etiology. Given the suspicion of atypical NMS, bromocriptine 2.5 mg three times daily was initiated. This led to the gradual resolution of his symptoms and a return to his baseline mental status. Diagnosing atypical NMS can be challenging and must be differentiated from similar disorders. Lithium toxicity can predispose patients to develop NMS.

Lithium Dispensed for Adults Aged ≥ 50 Years Between 2012 and 2021: Analyses of a 10% Sample of the Australian Pharmaceutical Benefits Scheme.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk factors, clinical correlates, and social functions of Chinese schizophrenia patients with drug-induced parkinsonism: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study.

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 co-linearity. 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. Clinical Trial Registration: Identifier: NCT02640911.

Fourteen-year trends in the prescribing patterns of pediatric bipolar patients discharged from two public mental hospitals in Taiwan.

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.