Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Evaluation of Antipsychotic-Induced Neuroleptic Malignant Syndrome Using a Self-Organizing Map.

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia.

Impact of Demographics and Insurance Coverage on Schizophrenia Treatment and Healthcare Resource Utilization Within an Integrated Healthcare System.

Purpose: Little is known about the impact of health disparities on antipsychotic treatment and healthcare resource utilization (HRU) among patients with schizophrenia. The objective of this analysis is to examine treatment patterns and HRU by age, race/ethnicity, and insurance coverage among patients with schizophrenia in an integrated delivery network (IDN). Patients and Methods: This cross-sectional study used electronic health record data from MedStar Health, an IDN in the Baltimore-Washington, DC, area. Patients were aged ≥18 years and had ≥2 outpatient encounters or ≥1 hospitalization with a diagnosis of schizophrenia between January 1, 2017 and March 31, 2021. Outcomes assessed included oral antipsychotic prescriptions, long-acting injectable antipsychotic (LAI) utilization, hospitalizations, emergency department (ED) visits, and outpatient visits. Analyses compared subgroups based on age, race/ethnicity (non-Hispanic Black, non-Hispanic White, and other), and type of insurance coverage at index (Medicare, Medicaid, and other) during 12 months of follow-up. Results: A total of 78.1% of patients had ≥1 prescription for an antipsychotic and 69.1% received ≥1 second-generation antipsychotic. Second-generation long-acting injectables (SGA LAI) were utilized by 9.0% of patients, with the elderly and Medicaid beneficiaries having the lowest SGA LAI utilization. Overall, 61.7% of patients had ≥1 hospitalization, 56.4% had ≥1 outpatient visit, and 50.5% had ≥1 ED visit. Hospitalizations and ED visits were most common in those 18 to 24 years of age and in Medicaid beneficiaries, whereas outpatient visits were more common for the elderly and Medicare beneficiaries. Conclusion: At the population level, the results indicate widespread underprescription/underutilization of antipsychotics that have been shown to improve clinical and economic outcomes in patients with schizophrenia, particularly SGA LAI. Within specific subpopulations, disparities in treatment selection and HRU were observed, suggesting the need for increased attention to at-risk groups to ensure consistent quality of care regardless of age, race/ethnicity, or insurance coverage.

Schizophrenia and antipsychotic medications present distinct and shared gut microbial composition: A meta-analysis.

There are some conflicting results regarding alterations of gut microbial composition in schizophrenia (SZ), even a few meta-analysis studies have addressed this field. Ignoring of antipsychotic medication effects may cause the large heterogeneity and impact on study results. This study is a meta-analysis to systematically evaluate composition of gut microbiota in patients with SZ, to elucidate the impact of antipsychotic use and reveal distinct and shared gut bacteria in SZ and antipsychotic medications. We re-analyzed the publicly available 16S rRNA-gene amplicon datasets by a standardized pipeline in QIIME2, used the natural log of response ratios as an effect index to directly and quantitatively compare composition of gut microbiota by random-effects meta-analysis with resampling tests in Metawin, ultimately to evaluate distinct abundance of gut bacteria. A total of 19 studies with 1968 participants (1067 patients with SZ and 901 healthy controls (HCs)) were included in this meta-analysis. The alterations of alpha diversity indices occurred in SZ on antipsychotics but not in drug-naïve or -free patients, while variation of beta diversity metrics appeared in SZ regardless of antipsychotic use. After antipsychotic treatment, reversed Simpson index, decreased observed species index and significant difference of Bray-Curtis distance were observed in patients. Especially, risperidone treatment increased the Shannon and Simpson indices. Noteworthy, three differed genera, including Lactobacillus, Roseburia and Dialister, were identified in both states of antipsychotic use. This meta-analysis is to provide a novel insight that SZ and antipsychotic medications present distinct and shared gut microbial composition.

Pharmacogenomics-assisted treatment versus standard of care in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia. METHODS: PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible. RESULTS: A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76-1.13), p < 0.001); I2 = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37-18.93), p = 0.01); I2 = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low. CONCLUSION: Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard.

Effects of synbiotic supplementation on the components of metabolic syndrome in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Antipsychotic drugs may have adverse effects on the components of metabolic syndrome. Previous studies have shown that changes in the intestinal microbiome are associated with metabolic disturbances in patients with schizophrenia. The objective of this study was to determine the effects of synbiotics on the components of metabolic syndrome as primary outcomes in patients with schizophrenia. Secondary outcomes were HbA1c, insulin resistance, LDL-c, and anthropometric measurements. METHODS: In this double-blind, placebo-controlled trial, seventy patients with schizophrenia receiving antipsychotic drugs who had at least two criteria of metabolic syndrome were randomly divided into two groups to receive either two capsules of a synbiotic supplement or a placebo daily for 8 weeks. Anthropometric indices and biochemical parameters were measured at baseline and after the intervention. RESULTS: Fifty-five patients completed the study. The synbiotic supplement significantly decreased waist circumference and HbA1C compared to placebo (-2.66 ± 4.20 vs. 3.03 ± 4.50 and - 0.26 ± 0.54 vs. 0.20 ± 0.75, respectively). Although BMI did not change significantly in the synbiotic + antipsychotic group, it increased in the placebo + antipsychotic group (-0.37 ± 1.00 vs. 0.61 ± 1.09 P < 0.5). LDL-c and triglyceride (TG) levels decreased significantly in the synbiotic + antipsychotic group, but the change was not significantly different from that of the placebo + antipsychotic group. FBS, HDL-c, systolic and diastolic blood pressure, insulin resistance, and total cholesterol were not significantly different between the two groups after intervention. CONCLUSION: Synbiotic supplement may decrease waist circumference, HbA1c, LDL and TG and prevent BMI increase in patients receiving antipsychotic drugs. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT Number: IRCT20090901002394N45), Date: 26-12-2019.

Psychiatrists effect on positive symptom severity and daily functioning during pharmacotherapy for first-episode psychosis patients.

Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients' psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients' education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients' symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists' training with the goal of improving patient outcomes.

Efficacy of pharmacological treatment in OCD comorbid with tic disorder: Systematic review and meta-analysis.

Up to 30% of subjects with obsessive compulsive disorder (OCD) also have a lifetime tic disorder. Several meta-analyses of pharmaceutical or psychotherapeutic interventions for the management of OCD have been published, but none specifically on patients with OCD comorbid with tics. The literature regarding pharmacological treatments of patients with this condition is mainly focused on studies of OCD. After a search of the Cochrane, EMBASE, PubMed, PsychINFO and Science Direct databases, we performed a proportion meta-analysis of the percentage of patients whose condition improved and a paired meta-analysis of the change in the OCD score (Y-BOCS). Twelve case reports were retained for qualitative analysis and 14 articles for meta-analysis. Case reports showed better efficacy of combined antidepressant-antipsychotic treatment for OCD comorbid with tic disorder. The meta-analysis showed an improvement in 29% [18-42] of patients with antidepressants. Although there was no significant difference with placebo add-on, in antidepressant-resistant OCD patients, adding an antipsychotic to the antidepressant regimen led to an increase in the number of patients who improved (67% [45-86] vs 7% [0-35]) and seemed to show a decrease in the Y-BOCS score (-10.06 [-20.38; 0.26] vs (-3.61 [-9.08; 13.85]). Our study provides new evidence on the pharmacological treatment of OCD comorbid with tics. In some patients, the condition is improved by a first-line antidepressant. In case of non-response or insufficient efficacy of antidepressants, add-on treatment with certain antipsychotics can be implemented.

The association between respiratory failure and psychotropic medications: A systematic review.

OBJECTIVE: To examine the association between psychotropic medication usage and respiratory failure. METHODS: A systematic search of Embase, PubMed, CINAHL, PsycINFO, and the Cochrane Trial Registry databases for publications that evaluated the association between respiratory failure and the use of psychotropic medications in patients with chronic mental health disorders was performed. RESULTS: Nine studies were included, with a total of 170,435 participants. There was no association between antidepressant use and respiratory failure reported in the antidepressant studies, however no formal odds ratio was reported in any of these studies. Three antipsychotic studies met inclusion criteria, which included a total of 169,919 participants. However, two of these studies were derived from overlapping datasets, and one of these studies was reported as an abstract. None controlled for the key confounder of smoking status. All three demonstrated an increased risk of respiratory failure with antipsychotic use (adjusted odds ratio ranged from 1.13 95% CI: 1.2-1.89; to 2.33 95% CI: 2.06-2.64). Two out of three antipsychotic studies had a low risk of bias. CONCLUSIONS: No clear association between antidepressants and respiratory failure was identified. Three studies examining antipsychotic medications and respiratory failure indicated an increased risk for respiratory failure. However, studies demonstrated significant heterogeneity and confounding factors (e.g. smoking status) and strategies to deal with these were absent. Two studies were derived from overlapping datasets and one study was an abstract. Given the signal towards increased risk of respiratory failure with antipsychotic medications, further reporting on this association through large matched and independent datasets is required to allow meta-analysis to quantify the nature and extent of this increased risk.

A retrospective review of intramuscular olanzapine and parenteral benzodiazepine coadministration in the emergency department.

Introduction: Acute agitation is a common presenting symptom in medical and mental health emergencies that may require pharmacologic intervention. There is a manufacturer recommendation against intramuscular coadministration of olanzapine with parenteral (intramuscular or intravenous) benzodiazepines despite a deficiency of high-quality evidence. The purpose of this study was to contribute to available literature regarding intramuscular olanzapine and parenteral benzodiazepine use in acutely agitated patients in the emergency department (ED). Methods: This was a single-center retrospective chart review of adult ED patients who received intramuscular olanzapine and a parenteral benzodiazepine within 2 hours. The composite primary endpoint evaluated the occurrence of cardiac or respiratory compromise within 2 hours of medication administration. Secondary endpoints mirrored the primary endpoint within 30 minutes and evaluated the occurrence of cardiac arrest or desaturation in the ED outside the 2-hour window. Results: One hundred eleven patients were included in the analysis, 64 (57.7%) of whom had documented vitals or oxygen status within 2 hours of medication administration. The composite primary endpoint occurred in 8 patients (12.5%), with only 1 patient requiring intervention with intravenous fluids. The secondary composite endpoint occurred in 2 (9.5%) of 21 patients with documented vitals or oxygen status within 30 minutes of treatment, neither of which required intervention. There were no identified events of intubation or significant cardiac events. Discussion: Until better evidence is available, this combination therapy should, at minimum, include appropriate patient monitoring. Future studies should investigate risk factors for serious adverse effects.

Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application.

The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis.

Drugs with glutamate-based mechanisms of action in psychiatry.

Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of treatment resistance with a consecutive number of ineffective trials. A growing number of studies suggest that drugs targeting glutamate receptors offer an opportunity for rapid therapeutic effect that may overcome the limitations of monoaminergic drugs. In this article, we present a review of glutamate-modulating drugs, their mechanism of action, as well as preclinical and clinical studies of their efficacy in treating mental disorders. Observations of the rapid, robust, and long-lasting effects of ketamine and ketamine encourages further research on drugs targeting glutamatergic transmission. A growing number of studies support the use of memantine and minocycline in major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts yield the potential to ameliorate depressive symptoms in patients with affective disorders. Drugs with mechanisms of action based on glutamate constitute a promising pharmacological group in the treatment of mental disorders that do not respond to standard methods of therapy. However, further research is needed on their efficacy, safety, dosage, interactions, and side effects, to determine their optimal clinical use.

Individualized multi-modal MRI biomarkers predict 1-year clinical outcome in first-episode drug-naïve schizophrenia patients.

Background: Antipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia. Methods: Structural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17). Results: ML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences. Conclusion: Our study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy.

Effectiveness of Vitamin E in Treatment of Antipsychotic-Induced Tardive Dyskinesia and Extrapyramidal Symptoms: A Case Report.

Antipsychotic medications, while crucial in managing severe psychiatric disorders such as schizophrenia and bipolar disorder, are frequently associated with extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). TD, characterized by repetitive, involuntary movements, especially of the face and limbs, poses a substantial clinical challenge due to its often irreversible nature. Conventional management strategies, including dose reduction and switching to atypical antipsychotics, frequently offer limited success, prompting exploration of alternative therapies. This case report highlights the effectiveness of vitamin E, a potent antioxidant, in treating a 28-year-old male with severe antipsychotic-induced EPS and TD, unresponsive to traditional therapies. The patient, who had been receiving paliperidone injections as part of his psychotic disorder treatment regimen, developed marked EPS, including muscle rigidity, a parkinsonian gait, significant motor disturbances as well as tardive dyskinesia. Despite discontinuation of paliperidone and initiation of procyclidine, propranolol, clonazepam, and omega-3 supplements, his symptoms persisted. Introduction of oral vitamin E at 400 IU daily led to a dramatic improvement, with an 80% reduction in EPS and TD symptoms within weeks. The patient's Abnormal Involuntary Movement Scale (AIMS) score decreased from 24 to 4, and his overall quality of life improved significantly. Gradual increase of vitamin E dosage to 1200 IU daily, coupled with tapering of other medications, eventually led to complete resolution of symptoms, as evidenced by an AIMS score of 0. The patient maintained symptom-free status during follow-up, with no recurrence of psychotic symptoms. This case underscores the potential role of vitamin E as a viable adjunctive treatment for TD, particularly in patients who do not respond adequately to conventional therapies. While the literature presents mixed evidence regarding vitamin E's effectiveness, this case adds to the growing body of research suggesting its benefits, especially when introduced early in the disease course. Further large-scale studies are warranted to establish the most effective treatment protocols and identify patient populations most likely to benefit from vitamin E therapy.

Age and sex differences in outpatient antipsychotic prescriptions for schizophrenia: a claims data study.

Most studies on antipsychotic efficacy and safety, including sex differences, focus on young schizophrenia patients. However, with an aging population, the number of older schizophrenia patients is increasing. This group faces challenges due to varying treatment responses and higher risks of adverse reactions, and guidelines often lack specific recommendations due to insufficient trials. Therefore, we investigated how age and sex influence antipsychotic prescribing practices in schizophrenia using the German Pharmacoepidemiological Research Database (GePaRD). We included patients diagnosed with schizophrenia (ICD-10 code F20.X) who had been prescribed at least one antipsychotic on an outpatient basis in at least two consecutive quarters in 2020, analyzing prescription data for 49,681 patients. Key findings include a notable preference for second-generation antipsychotics (SGAs) across all age groups, especially in younger patients, possibly due to their perceived better tolerability and efficacy. Treatment intensity with SGAs (expressed as the defined daily doses of SGAs per patient in 2020) initially increased with age, peaked among 35- to 44-year-olds, and then decreased, with the lowest treatment intensity in patients aged 65 years and older. The prescription patterns of specific SGAs and first-generation antipsychotics varied across age groups, highlighting the complexity of treatment decisions in schizophrenia management. Sex differences in prescription frequency and treatment intensity were also observed. The basic recommendation of the guideline to consider sex and age when prescribing antipsychotics therefore appears to be followed. Whether this prescribing practice is really optimal for older male and female schizophrenia patients, however, still needs to be proven in clinical trials.

Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics: a state-of-the-art clinical review.

INTRODUCTION: People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes. AREAS COVERED: We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations. EXPERT OPINION: To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v)choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate(second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.

Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

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.

Association of nursing home antipsychotic reduction policies with antipsychotic use in community dwellers with dementia.

BACKGROUND: Antipsychotic and other psychotropic medication use is prevalent among community-dwelling older adults with dementia despite the potential for adverse effects. Two Centers for Medicare & Medicaid Services (CMS) initiatives, the National Partnership to Improve Dementia Care ("the Partnership") and the Five Star Quality Rating System for antipsychotic use reporting, have been successful in reducing antipsychotic use in nursing home residents. We assessed if these initiatives had a spillover effect in antipsychotic and other psychotropic medication use among community dwellers with dementia due to potential overlap in prescribers across settings. METHODS: Among community-dwelling older adults with dementia, we examined psychotropic medication class use (i.e., antipsychotics, antidepressants, anxiolytics, anticonvulsants/mood stabilizers, antidementia) in 2010-2017 Medicare fee-for-service claims using interrupted time series analyses across three periods ("Pre-Partnership": July 1, 2010 to March 31, 2012; "Post-Partnership": April 1, 2012 to January 31, 2015; "Five Star Quality Rating": February 1, 2015 to December 31, 2017). RESULTS: We included 1,289,401 community dwellers with dementia contributing 26,609,697 person-months. The mean age was 80 years, most were female (70%), approximately 80% were non-Hispanic Whites, 10% were non-Hispanic Blacks, and 5% were Hispanic ethnicity. Antipsychotic use was declining pre-Partnership (ß = -0.06, 95% CI: -0.08, -0.05) and post-Partnership (ß = -0.02, 95% CI: -0.02, -0.01). Post-Five Star Quality Rating, antipsychotic use remained stable with a nearly flat slope (ß = -0.01, 95% CI: -0.01, 0.00). Anticonvulsant and antidepressant use increased and anxiolytic and antidementia medication use decreased among community-dwelling older adults with dementia. CONCLUSIONS: These two CMS policies on antipsychotic use for nursing home residents were not associated with a spillover effect to community-dwelling older adults with dementia. Strategies to monitor the appropriateness of psychotropic medication use may be warranted for community-dwellers with dementia.

Using qualitative exit interviews to explore schizophrenia burden and treatment experience in clinical trial patients.

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials. Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted. Results: Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning. Conclusion: Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients' views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies.