Dataset Information

Second-Generation Antipsychotic Drugs for Patients with Schizophrenia: Systematic Literature Review and Meta-analysis of Metabolic and Cardiovascular Side Effects.

ABSTRACT:

Background and objectives

Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized controlled trials (RCTs) and observational studies.

Methods

We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have been considered for meta-analysis. A test for the summary effect measure and heterogeneity (I² metric) was used.

Results

Seventy-nine papers were selected from 3076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR showed the highest decrease in fasting glucose. Lurasidone showed the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR.

Conclusions

Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies.

SUBMITTER: Rognoni C

PROVIDER: S-EPMC8004512 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundIt is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia.MethodsThis is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked.ResultsIn total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14-70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients.ConclusionStable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.

Project description:BackgroundTo examine the baseline metabolic monitoring (MetMon) for second generation antipsychotics (SGA) among patients with schizophrenia in the Veterans Integrated Service Network (VISN) 16 of the Veterans Health Administration (VHA).MethodsVISN16 electronic medical records for 10/2002-08/2005 were used to identify patients with schizophrenia who received a new episode of SGA treatment after 10/2003, in which the VISN 16 baseline MetMon program was implemented. Patients who underwent MetMon (MetMon+: either blood glucose or lipid testing records) were compared with patients who did not (MetMon-), on patient characteristics and resource utilization in the year prior to index treatment episode. A parsimonious logistic regression was used to identify predictors for MetMon+ with adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsOut of 4,709 patients, 3,568 (75.8%) underwent the baseline MetMon. Compared with the MetMon- group, the MetMon+ patients were found more likely to have baseline diagnoses or mediations for diabetes (OR [CI]: 2.336 [1.846-2.955]), dyslipidemia (2.439 [2.029-2.932]), and hypertension (1.497 [1.287-1.743]), substance use disorders (1.460 [1.257-1.696]), or to be recorded as obesity (2.052 [1.724-2.443]). Increased likelihood for monitoring were positively associated with number of antipsychotics during the previous year (FGA: 1.434 [1.129-1.821]; SGA: 1.503 [1.290-1.751]). Other significant predictors for monitoring were more augmentation episodes (1.580 [1.145-2.179]), more outpatient visits (1.007 [1.002-1.013])), hospitalization days (1.011 [1.007-1.015]), and longer duration of antipsychotic use (1.001 [1.001-1.001]). Among the MetMon+ group, approximately 38.9% patient had metabolic syndrome.DiscussionThis wide time window of 180 days, although congruent with the VHA guidelines for the baseline MetMon process, needs to be re-evaluated and narrowed down, so that optimally the monitoring event occurs at the time of receiving a new episode of SGA treatment. Future research will examine whether or not patients prescribed an SGA are assessed for metabolic syndrome following the index episode of antipsychotic therapy, and whether or not such baseline and follow-up monitoring programs in routine care are cost-effective.ConclusionThe baseline MetMon has been performed for a majority of the VISN 16 patients with schizophrenia prior to index SGA over the study period. Compared with MetMon- group, MetMon+ patients were more likely to be obese and manifest a more severe illness profile.

Project description:BackgroundAntipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking.MethodsWe will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group's Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework.DiscussionThis systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians.Systematic review registrationPROSPERO CRD42020175414.