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 (I 2 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.

Assessing cardiometabolic parameter monitoring in inpatients taking a second-generation antipsychotic: The CAMI-SGA study – a cross-sectional study

“…Therefore, even though the guidelines recommend to measure baseline CMPM with all antipsychotics, to increase external validity and clinical relevance, first generation antipsychotics, aripiprazole, lurasidone, ziprasidone, brexpiprazole and cariprazine were excluded as they were deemed at less metabolic risk as per national guidelines24 and recent network meta-analysis,32 and the two latter were unavailable on the Canadian market during the study time frame. We can also note some emerging data seem to put some doubts on strength of this broad affirmation 33. However, in clinical practice, it is recommended to adhere to these guidelines for all antipsychotics.…”

“…We can also note some emerging data seem to put some doubts on strength of this broad affirmation. 33 However, in clinical practice, it is recommended to adhere to these guidelines for all antipsychotics.…”

How to improve the physical health of people with severe mental illness? A multicentric randomized controlled trial on the efficacy of a lifestyle group intervention

“…First, they frequently adopt unhealthy lifestyle behaviours, characterized by lack of physical activity, unhealthy diet (rich in carbohydrate and fat), heavy smoking and use of alcohol or illicit substances [15][16][17][18][19]. Second, several psychotropic medications have metabolic side effects, further increasing the cardiometabolic risk [20][21][22][23][24][25][26].…”

Use of Psychoeducation for Psychotic Disorder Patients Treated With Modern, Long-Acting, Injected Antipsychotics

“…Many factors including poor life-style and food intake, poor attention to health needs and side effects of psychotropic drugs may impact on the metabolic outcome of patients affected by psychoses (3). Currently, the employment of second-and third-generation antipsychotics, such as serotonin-dopamine antagonists or dopamine partial agonists, are clinically preferred since are more effective on negative, affective and cognitive symptoms of psychosis (4). Nonetheless, newer antipsychotics may induce increases in bodyweight, insulin-resistance with long-term adverse physiological effects including type−2-diabetes mellitus, hypertension and dyslipidemia, in addition to obesity (4)(5)(6).…”

“…Currently, the employment of second-and third-generation antipsychotics, such as serotonin-dopamine antagonists or dopamine partial agonists, are clinically preferred since are more effective on negative, affective and cognitive symptoms of psychosis (4). Nonetheless, newer antipsychotics may induce increases in bodyweight, insulin-resistance with long-term adverse physiological effects including type−2-diabetes mellitus, hypertension and dyslipidemia, in addition to obesity (4)(5)(6). Also, it has been largely described that the prevalence of metabolic syndrome in patients treated with antipsychotics is approximately 40% (33.8-42.1%) in contrast to rates of 10.4-12.2% among psychosis un-medicated patients: some atypical antipsychotics such as olanzapine and risperidone were associated to higher weight gain among non-clozapine second generation antipsychotics, as well as risperidone and amisulpride were responsible for increasing serum prolactin (7).…”