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Introduction: Weight gain in the months/years after diagnosis/treatment of severe enduring mental illness (SMI) is a major predictor of future diabetes, dysmetabolic profile and increased risk of cardiometabolic diseases. There is limited data on the longer-term profile of weight change in people with a history of SMI and how this may differ between individuals. We here report a retrospective study on weight change over the 5 years following an SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community, with particular focus on comparing non-affective psychosis (NAP) vs affective psychosis (AP) diagnoses. Methods: We undertook an anonymised search in the Greater Manchester Care Record (GMCR). We reviewed the health records of anyone who had been diagnosed for the first time with first episode psychosis, schizophrenia, schizoaffective disorder, delusional disorder (non-affective psychosis = NAP) or affective psychosis (AP). We analysed body mass index (BMI) change in the 5-year period following the first prescription of antipsychotic medication. All individuals had taken an antipsychotic agent for at least 3 months. The 5-year follow-up point was anywhere between 2003 and 2023. Results: We identified 9125 people with the diagnoses above. NAP (n = 5618; 37.3% female) mean age 49.9 years; AP (n = 4131; 60.5% female) mean age 48.7 years. 27.0% of NAP were of non-White ethnicity vs 17.8% of AP individuals. A higher proportion of people diagnosed with NAP were in the highest quintile of social disadvantage 52.4% vs 39.5% for AP. There were no significant differences in baseline BMI profile. In a subsample with HbA1c data (n = 2103), mean HbA1c was higher in NAP at baseline (40.4 mmol/mol in NAP vs 36.7 mmol/mol for AP). At 5-year follow-up, there was similarity in both the overall % of individuals in the obese ≥ 30 kg/m2 category (39.8% NAP vs 39.7% AP), and % progressing from a normal healthy BMI transitioned to obese/overweight BMI (53.6% of NAP vs 55.6% with AP). 43.7% of those NAP with normal BMI remained at a healthy BMI vs 42.7% with AP. At 5-year follow-up for NAP, 83.1% of those with BMI ≥ 30 kg/m2 stayed in this category vs 81.5% of AP. Conclusion: The results of this real-world longitudinal cohort study suggest that the changes in BMI with treatment of non-affective psychosis vs bipolar disorder are not significantly different, while 43% maintain a healthy weight in the first 5 years following antipsychotic prescription. Key summary: We here report a longitudinal retrospective cohort study on weight change post-SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community with particular focus on a history of non-affective psychosis vs affective psychosis disorder. [ABSTRACT FROM AUTHOR]

Background Despite uncertain benefits, people with personality disorder are commonly treated with antipsychotic medication. Objective To investigate the association between antipsychotics and violent crimes and suicidal behaviour in individuals with personality disorder. Methods We used nationwide Danish registries to identify all individuals with diagnosed personality disorder aged 18--64 years during 2007 to 2016. Antipsychotics were recorded in dispensed prescriptions, and individuals were followed up for policerecorded suspicions for violent crimes and healthcare presentations of suicidal behaviour. We applied a withinindividual design where outcome rates for individuals with personality disorder during medicated periods were compared with rates during non-medicated periods. Findings The cohort included 166 328 people with diagnosed personality disorder, of whom 79 253 were prescribed antipsychotics, presented at least one outcome and were thus included in the within-individual analyses. Compared with periods when individuals were not on antipsychotic medication, violent crime suspicions were 40% lower (incident rate ratio (IRR) 0.60, 95% CI 0.55 to 0.63) in men and 10% lower (IRR 0.90, 95% CI 0.79 to 1.01) in women, while rates of suicidal behaviour were 32% lower both in men (IRR 0.68, 95% CI 0.66 to 0.71) and in women (IRR 0.68, 95% CI 0.65 to 0.70). In subgroup analyses, the magnitude of the association varied across specific personality disorders for criminal outcomes but less for suicidal behaviour, with largest association in dissocial personality disorder for violent criminality (IRR 0.53, 95% CI 0.47 to 0.59). Conclusions Treatment with antipsychotics was associated with reduced risks for violent crime suspicions and suicidal behaviour among individuals with personality disorder. Clinical implications Potential effects of antipsychotics on suicidal behaviour and violence should be taken into account when considering treatment options for people with personality disorders. [ABSTRACT FROM AUTHOR]

Although olanzapine remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability concerns related to its weight and metabolic profile. Olanzapine-samidorphan combination tablets (OLZ/SAM), branded as Lybalvi, is a newly FDA approved formulation aimed at attenuating antipsychotic induced weight gain via modulation of the endogenous opioid system with samidorphan, while retaining the robust antipsychotic efficacy of olanzapine. We reviewed the published literature of OLZ/SAM for the management of schizophrenia using the US National Library of Medicine's PubMed.gov resource. Topics covered in this narrative review include the pharmacokinetics, pharmacodynamics, efficacy, and tolerability of OLZ/SAM. OLZ/SAM is an effective and well-tolerated pharmacologic option in mitigating olanzapine induced weight gain while retaining olanzapine's efficacy. OLZ/SAM cumulatively tends to attenuate weight gain rather than promote weight loss. Effect on metabolic laboratory variables appears limited. Additional research will be needed to determine its effectiveness compared to alternative strategies to attenuate antipsychotic induced weight gain. [ABSTRACT FROM AUTHOR]

Side effects of antipsychotic drugs play a key role in nonadherence of treatment in schizophrenia spectrum disorders (SSD). While clinical observations suggest that side effect variability between patients may be considerable, statistical evidence is required to confirm this. Here, we hypothesized to find larger side effect variability under treatment compared with control. We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD treated with 1 out of 14 antipsychotics. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels, and corrected QT (QTc) times were extracted. The outcome measure was the variability ratio of treatment to control for individual antipsychotic drugs and the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. We included N = 16 578 patients for weight gain, N = 16 633 patients for prolactin levels, and N = 10 384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02–1.14; P =.004) and prolactin levels (VR = 1.38; 95% CI: 1.17–1.62; P <.001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98–1.12; P = 0.135). We found marked differences between individual antipsychotics and increased variability in side effects in patients under treatment with antipsychotics suggesting that subgroups of patients or individual patients may benefit from treatment allocation through stratified or personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: A post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia. Methods: In the DB trial, patients were randomised to receive lurasidone or risperidone for 12 months. In OLE, all patients received lurasidone for an additional 6 months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression–Severity scale, and Montgomery–Åsberg Depression Rating Scale. Results: In the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically significant increases in prolactin and fasting glucose levels. The proportion of patients with metabolic syndrome was significantly lower in patients treated with lurasidone versus risperidone at the end of the DB trial (25.5% vs 40.4%; p = 0.0177). During OLE, patients switching from risperidone to lurasidone experienced a reduction in weight and prolactin levels; those continuing treatment with lurasidone experienced minimal changes in metabolic variables and prolactin. At the end of OLE, the proportion of patients with metabolic syndrome was no longer significantly different between groups (23.5% vs 31.5%; p = not significant). Efficacy outcomes were generally similar between groups during the DB trial, and were maintained during OLE. Conclusion: Lurasidone was generally well tolerated and effective in clinically stable schizophrenia patients over the long term. Lurasidone was also generally well tolerated and maintained effectiveness over 6 months in patients switching from risperidone. Patients switching from risperidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone's long-term effectiveness and favourable metabolic profile in patients with schizophrenia. Trial Registration: ClinicalTrials.gov identifier NCT00641745. [ABSTRACT FROM AUTHOR]

Introduction: Lurasidone is an atypical antipsychotic that was approved in Europe in 2014 for the treatment of schizophrenia in adults aged ≥ 18 years. Clinical experience with lurasidone in Europe is currently limited, and there is therefore a need to provide practical guidance on using lurasidone for the treatment of adults with schizophrenia. Methods: A panel of European psychiatrists with extensive experience of prescribing lurasidone was convened to provide recommendations on using lurasidone to treat adults with schizophrenia. Results: Extensive evidence from clinical trials and the panel's clinical experience suggest that lurasidone is as effective as other atypical agents, with the possible exception of clozapine. Lurasidone is associated with a lower propensity for metabolic side effects (in particular, weight gain) and hyperprolactinaemia than most other atypical antipsychotics and has a relatively benign neurocognitive side effect profile. Patients switching to lurasidone from another antipsychotic may experience weight reduction and/or improvements in the ability to focus/concentrate. Most side effects with lurasidone (such as somnolence) are transitory, easily managed and/or ameliorated by dose adjustment. Akathisia and extrapyramidal symptoms may occur in a minority of patients, but these can be managed effectively with dose adjustment, adjunctive therapy and/or psychosocial intervention. Conclusions: Given the crucial importance of addressing the physical as well as mental healthcare needs of patients, lurasidone is a rational therapeutic choice for adults with schizophrenia, both in the acute setting and over the long term. Funding: Sunovion Pharmaceuticals Europe Ltd. [ABSTRACT FROM AUTHOR]

Introduction Clozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation. Methods and analysis A 24-week double-blind placebocontrolled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants. Ethics and dissemination Ethics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds. [ABSTRACT FROM AUTHOR]

Metabolic disorders (MDs) like obesity, dyslipidemia, and type 2 diabetes are more frequently observed in patients diagnosed with psychiatric disorders undergoing treatment with antipsychotics, particularly atypical agents, than in the general population. The second generation of antidiabetics (SGAD) has been associated with cardiovascular benefits in large clinical trials which represent an important advantage over first-generation agents and might be of interest in the psychiatric population where multiple risk factors for cardiovascular disease (e.g., smoking, lack of exercise, and lack of healthy diet) are common occurrences. Therefore, this systematic review focused on the evaluation of the glucagon-like peptide-1 receptor agonists (GLP1-RAs), as a representative of the SGAD, to determine whether these agents may be recommended in patients with psychiatric disorders and MDs. For analysis, three electronic databases and clinical trial registers were explored for papers published between January 2000 and November 2022. After applying the inclusion and exclusion criteria, 20 clinical and preclinical trials, therapeutic guidelines, and meta-analyses were reviewed, and clinical recommendations were formulated. The large majority of the reviewed data (nine papers) were graded 'moderate' based on the GRADE criteria. The efficacy and tolerability of liraglutide and exenatide in the management of antipsychotic-induced MDs were supported by evidence of average quality, while the results regarding other GLP-1RAs were not sufficient to formulate a recommendation for their administration in this specific population. Clozapine and olanzapine had the most negative consequences on body weight, glycemic, and lipid metabolism. Therefore, careful monitoring of metabolic parameters is required when these are prescribed. Liraglutide and exenatide may be recommended as augmentative agents to metformin therapy, especially in patients receiving these two atypical antipsychotics, but most of the reviewed data supported the efficacy of GLP-1RAs only during the treatment administration. The two follow-up studies retrieved in the literature reported modest effects after GLP-1RA discontinuation after 1 year; therefore, long-term monitoring of metabolic parameters is required. More research is needed, and three randomized clinical trials are already ongoing, to evaluate the effects of GLP-1RAs in decreasing body weight, but also on other important metabolic variables, such as HbA1c status, fasting glucose levels, and lipid levels in patients receiving antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Metabolic dysfunctions have been reported in patients diagnosed with severe mental illnesses who are undergoing treatment with antipsychotics, especially second-generation agents. Sodium-glucose co-transporter 2 inhibitors (SGLT2Is) and glucagon-like peptide receptor agonists are new-generation antidiabetics whose favourable effects in the treatment of diabetes mellitus in the non-psychiatric population may raise interest in their use in patients presenting with severe mental illnesses and metabolic comorbidities possibly related to the use of antipsychotics. The objectives of this review were to investigate the evidence to support the use of SGLT2Is in this population and to find the most important aspects that need to be addressed by future research. A total of one preclinical trial, two guideline-format clinical recommendations, one systematic review and one case report were found, and their conclusions were analysed. The results support the following conclusions: i) SGLT2Is may be combined with metformin in selected cases of type 2 diabetes mellitus in the context of antipsychotic treatment, as they have been associated with favourable metabolic effects; and ii) data for the recommendation of SGLT2Is as second-line treatment in patients with diabetes mellitus who are also treated with olanzapine or clozapine are supported by very limited preclinical and clinical evidence. Further high-quality, large-scale research is needed in the field of the management of metabolic dysfunctions in patients with severe psychiatric illnesses who undergo treatment with second-generation antipsychotics. [ABSTRACT FROM AUTHOR]