Switching antipsychotics as a treatment strategy for antipsychotic-induced weight gain and dyslipidemia.
ABSTRACT Patients taking antipsychotic medications for psychiatric disorders also have many risk factors for medical comorbidities and early death. While these risk factors were present before the arrival of the newer antipsychotic medications, the overall risk factor burden is exacerbated for those high-risk patients whose antipsychotic therapy causes or aggravates obesity or dyslipidemia. Therefore, there is an urgent need for effective interventions to address problems related to the additional iatrogenic burden from weight gain and dyslipidemias caused by antipsychotic medications. For patients with schizophrenia, complete discontinuation of antipsychotic therapy is not advisable and, therefore, pharmacologic options are narrowed to dose adjustments, adding adjunctive agents to induce weight loss, discontinuation of other adjunctive agents associated with weight gain, or changing the antipsychotic medication ("switching"). This article reviews the evidence showing that relative to other possible treatment options, switching to an antipsychotic with a lower propensity to induce weight gain or dyslipidemia can be effective for reversing the weight gain and dyslipidemia caused by previous antipsychotic treatment.
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ABSTRACT: Antipsychotic (AP) treatment-emergent extrapyramidal symptoms (EPS) are acute adverse reactions of APs. The aim of the present study is to analyze gene-gene interactions in nine genes related to the mTOR pathway, in order to develop genetic predictors of the appearance of EPS. 243 subjects (78 presenting EPS: 165 not) from three cohorts participated in the present study: Cohort 1, patients treated with risperidone, (n=114); Cohort 2, patients treated with APs other than risperidone (n=102); Cohort 3, AP-naïve patients with first-episode psychosis treated with risperidone, paliperidone or amisulpride, n=27. We analyzed gene-gene interactions by multifactor dimensionality reduction assay (MDR). In Cohort 1, we identified a four-way interaction, including the rs1130214 (AKT1), rs456998 (FCHSD1), rs7211818 (Raptor) and rs1053639 (DDIT4), that correctly predicted 97 of the 114 patients (85% accuracy). We validated the predictive power of the four-way interaction in Cohort 2 and in Cohort 3 with 86% and 88% accuracy respectively. We develop and validate a powerful pharmacogenetic predictor of AP-induced EPS. For the first time, the mTOR pathway has been related to EPS susceptibility and AP response. However, validation in larger and independent populations will be necessary for optimal generalization. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 11/2014; 25(1). · 3.68 Impact Factor
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ABSTRACT: This observational study evaluates the long-term outcome of switching to ziprasidone in patients with schizophrenia in the clinical practice setting. Patients (208) with schizophrenia who had been switched to ziprasidone monotherapy due to partial response or tolerability problems were followed for 1 year. Efficacy was assessed at baseline and months 1, 3, and 12 with Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-severity (CGI-S), and CGI-improvement. Quality of life, functionality, and safety measures, including metabolic parameters, were also assessed; 195 subjects comprised the per protocol analysis population. A reduction > or = 30% in BPRS total score was observed in 42.5% of the subjects. Mean scores of the BPRS (global and positive and negative clusters), CGI-S and CGI-I significantly decreased at endpoint (p < 0.001). Ziprasidone treatment was also associated with statistically significant improvements in the GAF, WHO-DAS-II, and SF-12. After 1-year follow-up, a mean weight decrease of -1.6 kg (p < 0.05) was observed. Mean levels of LDL cholesterol and triglycerides also decreased (p < 0.01) while HDL cholesterol levels increased (p < 0.05) at endpoint. No significant changes in mean glucose levels at study end were detected. These findings suggest that switching to ziprasidone is effective and well tolerated in patients with schizophrenia requiring a change in antipsychotic medication.The International Journal of Psychiatry in Medicine 01/2013; 45(2):125-42. · 0.81 Impact Factor
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ABSTRACT: To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone. Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion of patients with treatment emergent adverse events (AEs), serious AEs, or who discontinued due to AEs. Secondary endpoints included metabolic variables and measures of extrapyramidal symptoms and akathisia, as well as the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), and the Calgary Depression Scale for Schizophrenia (CDSS). The study was conducted from August 2010 to November 2011. Of the 198 patients who completed the 6-week core study, 149 (75.3%) entered the extension study and 148 received study medication. A total of 98 patients (65.8%) completed the 6-month extension study. Lurasidone 40, 80, and 120 mg were the modal daily doses for 19 (12.8%), 65 (43.9%), and 64 (43.2%) of patients, respectively. Overall mean (SD) daily lurasidone dose was 102.0 mg (77.1). The most commonly reported AEs were insomnia (13 patients [8.8%]), nausea (13 patients [8.8%]), akathisia (12 patients [8.1%]), and anxiety (9 patients [6.1%]). A total of 16 patients (10.8%) had at least one AE leading to discontinuation from the study. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, lipids, glucose, insulin, or prolactin. Movement disorder rating scales did not demonstrate meaningful changes. Treatment failure (defined as any occurrence of discontinuation due to insufficient clinical response, exacerbation of underlying disease, or AE) was observed for 19 patients (12.8% of patients entering) and median time to treatment failure was 58 days (95% CI 22-86). The discontinuation rate due to any cause was 50/148 (33.8%), and median time to discontinuation was 62 days (95% CI 30-75). The mean PANSS total score, mean CGI-S score, and mean CDSS score decreased consistently from core study baseline across extension visits, indicating an improvement in overall condition. In this 6-month, open-label extension study, treatment with lurasidone was generally well-tolerated with sustained improvement in efficacy measures observed in outpatients with schizophrenia or schizoaffective disorder who had switched to lurasidone from a broad range of antipsychotic agents.CNS spectrums 12/2013; · 1.30 Impact Factor