Antipsychotic-induced Weight Gain Research Articles

The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis

Abstract Background Weight gain and metabolic complications are substantial adverse effects associated with second-generation antipsychotics. However, comprehensive guidelines for managing antipsychotic-induced weight gain are lacking. Methods This review included all double-blind, placebo-controlled studies investigating metformin’s effectiveness in addressing antipsychotic-related weight gain. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov for relevant studies from the inception to 2024. A random-effects model was used for the meta-analysis. Results This meta-analysis, including 20 studies with 1070 patients, revealed that metformin significantly surpassed placebo in attenuating weight gain in patients receiving antipsychotics. The mean weight change with metformin was −3.32 kg [95% confidence interval (CI): −4.57 to −2.07]. Additionally, metformin use resulted in a marked decrease in body mass index [−1.24 kg/m2 (95% CI: −1.70 to −0.77)]. Metformin could maintain the effects from 12 to 24 weeks. Conclusions This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research to validate our findings.

Protective effects of menthol against olanzapine-induced metabolic alterations in female mice

AimMetabolic comorbidities such as obesity type 2 diabetes, insulin resistance, glucose intolerance, dyslipidemia are the major contributors for lower life expectancy and reduced patient compliance during antipsychotic therapy in patients with severe mental illnesses such as schizophrenia, bipolar disorder, and depression. TRPM8 activation by menthol is also reported to alleviate high fat diet-induced obesity in mice. Additionally, this TRPM8 activation leads to increase in gene expression of thermogenic genes in white adipocytes and dietary menthol was found to increase browning of WAT along with improved glucose utilization. Therefore, we aimed to evaluate the plausible role of TRPM8 channels in olanzapine-induced metabolic alterations in female balb/c mice. Methods6 weeks olanzapine (6 mg kg−1, per oral) model was used in female balb/c mice. Pharmacological manipulation of TRPM8 channel was done using menthol and N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide (AMTB), the agonist and antagonist respectively. Key resultsMenthol co-treatment for six weeks prevented olanzapine-induced metabolic alterations such as weight gain, increased food intake, decreased energy expenditure, adiposity, liver lipid accumulation, systemic inflammation and insulin resistance. Although no significant change in TRPM8 mRNA expression was found in the hypothalamus, however, some of the protective effects of menthol were absent in presence of AMTB indicating possible involvement of TRPM8 channels. ConclusionOur results suggest possible therapeutic implications of menthol in the management of antipsychotic-induced weight gain and other metabolic alterations.

The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta-analysis.

Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic-induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously. A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness. A meta-analysis was also completed where applicable. We identified two categories of studies for the meta-analysis. Category 1 included three studies, which compared measures of AP adherence or discontinuation across BMI classes/degrees of self-reported weight gain. When compared to normal weight individuals receiving APs or those who did not report AIWG, individuals who were either overweight or obese or reported weight gain in relation to AP use had an increased odds of AP nonadherence (OR 2.37; 95% CI 1.51-3.73; p = 0.0002). Category 2 had 14 studies which compared measures of discontinuation related to weight gain reported as an adverse effect across different APs. Olanzapine was associated with a 3.32 times (95% CI 2.32-4.74; p < 0.00001) increased likelihood of nonadherence or discontinuation when compared to other APs with lower weight gain liabilities. Similarly, APs with moderate weight gain liability (paliperidone, risperidone, and quetiapine) increased the odds of nonadherence or discontinuation by 2.25 (95% CI 1.31-3.87; p = 0.003) when compared to APs considered to have lower weight gain liability (i.e. haloperidol and aripiprazole). The qualitative summary also confirmed these findings. This review and meta-analysis suggests that AIWG influences medication nonadherence/discontinuation, whereby APs with higher weight gain liability are associated with nonadherence/discontinuation. Additional studies are needed to confirm these findings.

GLP-1 receptor agonists and weight loss in schizophrenia - past, present, and future.

People with schizophrenia experience three to five times higher prevalence of diabetes and obesity than the general population, contributing to a 20-year reduced lifespan. The impacts of weight gain extend beyond physical health, affecting people's self-esteem, quality of life, and triggering treatment nonadherence, leading to relapse and deteriorations in health. Clinical guidelines recommend patients with antipsychotic-induced weight gain are treated with cognitive behaviour therapy and lifestyle changes; however, effective treatments for obesity in schizophrenia are critically lacking. Glucagon-like peptide-1 receptor agonists (GLP-RAs) have shown large effects in weight loss in the general population; however, effects are less clear in people with schizophrenia. This review aims to assess the clinical trials that have been completed, are in progress, and directions for future trials. To date, six clinical trials have been completed, four of which have published their findings. Three further trials are currently in progress. Results from completed trials suggest that GLP-1RAs decrease weight in people with schizophrenia, however effect sizes are mostly smaller than studies based on the general population. Future trials could focus on dual or triple agonist agents, and/or explore the effects of GLP-1 s at antipsychotic medication commencement, to potentially prevent antipsychotic weight gain.

Informing the development of antipsychotic-induced weight gain management guidance: patient experiences and preferences - qualitative descriptive study.

Antipsychotic-induced weight gain (AIWG) is a substantial contributor to high obesity rates in psychiatry. Limited management guidance exists to inform clinical practice, and individuals with experience of managing AIWG have had no or minimal input into its development. A lack of empirical research outlining patient values and preferences for management also exists. Recommendations addressing weight management in psychiatry may be distinctly susceptible to ideology and sociocultural values regarding intervention appropriateness and expectations of self-management, reinforcing the need for co-produced management guidance. This study is the first to ask: how do individuals conceptualise preferred AIWG management and how can this be realised in practice? 1. Explore the management experiences of individuals with unwanted AIWG. 2. Elicit their values and preferences regarding preferred management. Qualitative descriptive methodology informed study design. A total of 17 participants took part in semi-structured interviews. Data analysis was undertaken using reflexive thematic analysis. Participants reported that clinicians largely overestimated AIWG manageability using dietary and lifestyle changes. They also reported difficulties accessing alternative management interventions, including a change in antipsychotic and/or pharmacological adjuncts. Participants reported current management guidance is oversimplified, lacks the specificity and scope required, and endorses a 'one-size-fits-all' management approach to an extensively heterogenous side-effect. Participants expressed a preference for collaborative AIWG management and guidance that prioritises early intervention using the range of evidence-based management interventions, tailored according to AIWG risk, participant ability and participant preference. Integration of this research into guideline development will help ensure recommendations are relevant and applicable, and that individual preferences are represented.

Glucagon-like peptide agonists for weight management in antipsychotic-induced weight gain: A systematic review and meta-analysis.

Managing body weight in patients with antipsychotic-induced weight gain (AIWG) is challenging. Besides lifestyle interventions, pharmacological interventions may contribute to weight loss. This systematic review and meta-analysis evaluated the effect on weight loss and adverse effects of glucagon-like peptide-1 (GLP-1) agonists in patients with AIWG. Following PRISMA guidelines, we performed a meta-analysis of blinded and open-label randomised controlled trials (RCTs), non-randomised controlled trials and cohort studies that evaluated treatment with GLP-1 in patients with AIWG, regardless of psychiatric diagnosis. PubMed, Embase, PsycINFO and Cochrane Library databases were searched. Primary outcome measures were changes in body weight and BMI. Secondary outcomes were changes in adverse effects and severity of psychopathology due to GLP-1 agonists. Only data for exenatide and liraglutide could be included, that is, five RCTs and one cohort study. For exenatide the mean weight loss was -2.48 kg (95% Confidence Interval (CI) -5.12 to +0.64; p = 0.07), for liraglutide the mean weight loss was -4.70 kg (95% CI -4.85 to -4.56; p < 0.001). The mean change in BMI was -0.82 (95% CI -1.56 to -0.09; p = 0.03) in the exenatide groups and -1.52 (95% CI -1.83 to -1.22; p < 0.001) in the liraglutide groups. Exenatide and liraglutide did not adversely affect psychopathology. The most common adverse events were nausea, vomiting, and diarrhoea. The GLP-1 agonists exenatide and liraglutide are promising drugs for inducing weight loss in patients with AIWG. The adverse effects are acceptable, and the addition of GLP-1 does not increase the severity of psychopathology. However, more research is needed.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial

BackgroundWeight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism.MethodsPatients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8.ResultsSixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group.ConclusionsThese findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients.Trial registrationClinicalTrials.gov NCT03451734.

Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis

ObjectiveAntipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). MethodsThe data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. ResultsThe drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (−8.0 kg; −16. to −0.21), metformin 750 mg + lifestyle modification (−7.5 kg; −12 to −2.8), topiramate 200 mg (−7 kg; −10 to −3.4), metformin 750 mg (−5.7 kg; −9.3 to −2.1), topiramate 100 mg (−5.7 kg; −8.8 to −2.5), topiramate 50 mg (−5.2 kg; −10 to −0.57), liraglutide 1.8 mg (−5.2 kg; −10., −0.080), sibutramine 15 mg (−4.5 kg; −8.9 to −0.59), nizatidine 300 mg (−3.0 kg; −5.9 to −0.23) and metformin 1000 mg (−2.3 kg; −4.6 to −0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. ConclusionMetformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence.

Are Opioid Receptor Antagonists Effective at Treating Antipsychotic-Induced Weight Gain? A Systematic Review and Meta-Analysis

Are Opioid Receptor Antagonists Effective at Treating Antipsychotic-Induced Weight Gain? A Systematic Review and Meta-Analysis

Development of antipsychotic-induced weight gain management guidance: patient experiences and preferences - a qualitative descriptive study

Abstract Introduction It is estimated that 50% of patients with a severe mental illness (SMI) do not adhere to their medication regimen. Antipsychotic-induced weight gain (AIWG) is one of the most common reasons for patient disengagement with treatment.[1] Clinically significant weight gain has been linked to almost all antipsychotics and contributes significantly to the 2-3-fold higher rates of obesity seen in psychiatry.[2] Given the personal, social, and healthcare costs of overweight, obesity and relapse of mental illness, effectively managing AIWG is a priority for patients, clinicians, and policymakers. However, effectively managing AIWG is challenging. Sparse guidance for clinicians invariably contributes to management complexity. An important barrier to the development of high-quality AIWG management guidance is the lack of empirical research assessing patient values and preferences for management and other key guideline decision-making criteria including acceptability, feasibility, and equity considerations. Integration of patient experiences and preferences for management into guidance informing practice is essential to ensure recommendation relevance, applicability, and transferability. Aim To elicit the values and preferences of those with lived experience of AIWG regarding preferred management. Methods Qualitative descriptive methodology was used as it avoids high-level interpretation and theory development in data analysis and results in outputs that can be more readily implementable by policymakers and guideline developers. The study recruited adult outpatients attending a secondary psychiatric care setting with a diagnosis of a SMI and experience of AIWG. Purposive sampling informed recruitment whereby participants who had a diverse range of experiences of AIWG were recruited. Participants took part in online semi-structured interviews. Reflexive thematic analysis informed data analysis. Results Seventeen participants were recruited (24% male; mean age: 51.7 years [range: 26-66]). Participants conceptualised preferred AIWG management as being individualised, proactive, collaborative, and holistic. Participants were asked how the tenets of preferred management could be realised in practice and within clinician management guidance. Results are summarised in Figure 1. Conclusion Use of this research by guideline developers will provide opportunities to maximise the impact of recommendations in practice for those funding, providing, and using services. The opportunity to include a culturally diverse group was unavailable, which may limit transferability of study findings.

Birth weight, leptin and adiponectin in patients initiating clozapine

IntroductionPsychotic patients often require pharmacological treatment, which may prove ineffective, leading to treatment-resistant psychosis necessitating the use of clozapine. However, the emergence of side effects can result in discontinuation, potentially triggering a relapse of psychotic symptoms. One significant side effect is antipsychotic-induced weight gain which, over time, can lead to adverse metabolic events. Recent translational research is evaluating the impact of prenatal factors on the metabolic outcomes of psychotic patients, using a surrogate marker of the intrauterine milieu such as birth weight (BW).ObjectivesWe aim to evaluate the changes in leptin, adiponectin, and insulin levels in patients with treatment-resistant psychosis who initiate clozapine treatment due to persistent psychotic symptoms.MethodsSubjects older than 18 years with a diagnostic of a major mental disorder and initiating clozapine were enrolled in this 18-months longitudinal study. Neurohormones levels, including leptin, adiponeptin, and insulin were measured at baseline, 8 and 18 months during follow-up. Statistical analysis were conducted by using a fixed-effects model.ResultsA total of 23 subjects initiating clozapine were evaluated during the initial mandatory 18-week period. Neurohormones, specifically leptin and adiponectin, were measured at three time points: baseline, 8 weeks, and 18 weeks. The changes in leptin levels were significantly associated with birth BW with sex differences, being inversely correlated only in females. Adiponectin was significantly associated with BW, being inversely correlated in males. Conversely, there was no observed association between insulin levels and BW.ConclusionsOur findings highlight the significance of prenatal factors in influencing the subsequent evolution of neurohormones in individuals initiating clozapine treatment. This suggests that subjects with lower BW tend to exhibit elevated neurohormone values, emphasizing the role of prenatal events in this context.Disclosure of InterestNone Declared

Associations between antipsychotics-induced weight gain and brain networks of impulsivity

Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of “at risk” patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21–27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22–33, N = 102) and middle-aged (56 years, IQR = 51–62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (β = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = −0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (β = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.

Trajectories and Predictors for the Development of Clinically Significant Weight Gain in Children and Adolescents Prescribed Second-Generation Antipsychotics.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation.

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10-9) and rs3824417 in PTPRD (P = 3.348 × 10-9) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10-4) and triglycerides (P = 2.06 × 10-3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R2 = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.

The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial

Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).

Effectiveness of lifestyle intervention on prevention/management of antipsychotic-induced weight gain among persons with severe mental illness: A systematic review and meta-analysis.

Individualized lifestyle interventions using motivational interviewing (MI) approach are recommended for persons with severe mental illness (SMI) for effective weight management. The aim of this meta-analysis was to assess the effectiveness of various lifestyle interventions that addressed obesity among persons with SMI. Twelve RCTs were assessed by individual reviewers using revised cochrane risk-of-bias tool (RoB 2). The standardized mean difference (SMD) was calculated with a 95% CI. The age of participants was between 18 and 70 years. Waist circumference showed an SMD of -0.09 (-0.22, 0.03), weight -0.03 (-0.10, 0.15) and BMI -0.07 (-0.07, 0.22). The findings in this meta-analysis revealed that though lifestyle interventions were statistically insignificant in reducing antipsychotic induced weight gain among persons with SMI, they show changes in intervention group. Psychosocial management along with lifestyle interventions, and MI are effective in the management of antipsychotic induced weight gain.

A Realist Evaluation of Social Care Practitioners' Experiences With and Understanding of Applied Healthcare Research.

Social care practitioners are often under-represented in research activity and output. Evidence-based practice enables social care practitioners to develop/engage the skills to evaluate evidence and be more actively involved in research. REalist Synthesis Of non-pharmacologicaL interVEntions for antipsychotic-induced weight gain (RESOLVE) is a NIHR-funded study where realist synthesis is used to understand and explain how, why, for whom, and in what contexts non-pharmacological interventions help service users, with severe mental illness, to manage antipsychotic-induced weight gain. Social care practitioners are a key part of the team providing care for people living with severe mental illness and therefore supporting antipsychotic-induced weight gain. The current study, RESOLVE 2, uses realist evaluation and RESOLVE as an illustrative example to help understand why and how social care practitioners engage (or not) with research. Semi-structured, audio-recorded interviews will be undertaken with a purposive sample of approximately 20 social care practitioners working with people who have severe mental illness, are treated with antipsychotics, and have experienced weight gain. Participants will be recruited from NHS Trusts and recruitment avenues such as social media and personal networks. Topics discussed during interviews will include barriers and facilitators to engagement in research, current, and past engagement as well as recommendations for researchers and other practitioners. Interview recordings will be transcribed verbatim and analyzed using realist evaluation which will allow in-depth causal explanations for research engagement. Better understanding of research engagement by social care practitioners will allow for evidence-based practice and better patient outcomes within these settings.

Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis.

Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

Association of clinical parameters and polygenic risk scores for body mass index, schizophrenia, and diabetes with antipsychotic-induced weight gain

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG.200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits.PRSs for BMI (β = 3.78; p = 0.0041), schizophrenia (β = 5.38; p = 0.021) and diabetes type 2 (β = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10−6.Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples.