Related Experiment Video
Updated: Nov 18, 2025
Self-Administration of Drugs in Mouse Models of Feeding and Obesity
Published on: June 8, 2021
Does Switching Antipsychotics Ameliorate Weight Gain in Patients With Severe Mental Illness? A Systematic Review and
Dan Siskind1,2, Erin Gallagher1,2, Karl Winckel3,4
1Metro South Addiction and Mental Health Service, Brisbane, Australia.
Objective:
Obesity and adverse metabolic outcomes in patients with severe mental illness are clinically significant but potentially preventable. Importantly, the evidence for switching to antipsychotics to reduce cardiometabolic burden is unclear.
Method:
PubMED, Embase, PsycINFO, and Cochrane were searched from inception to March 8, 2020. Articles reporting weight and metabolic changes after antipsychotic switching vs staying on the previous antipsychotic were meta-analyzed both across and within group.
Results:
Of 61 identified studies, 59 were meta-analyzed (40% rated high quality). In the switch-vs-stay pairwise meta-analyses, only aripiprazole significantly reduced weight (-5.52 kg, 95% CI -10.63, -0.42, P = .03), while olanzapine significantly increased weight (2.46 kg, 95% CI 0.34, 4.57, P = .02). Switching to aripiprazole also significantly improved fasting glucose (-3.99 mg/dl, 95% CI -7.34, -0.64, P = .02) and triglycerides (-31.03 mg/dl, 95% CI -48.73, -13.34, P = .0001). Dropout and psychosis ratings did not differ between switch and stay groups for aripiprazole and olanzapine. In before-to-after switch meta-analyses, aripiprazole (-1.96 kg, 95% CI -3.07, -0.85, P < .001) and ziprasidone (-2.22 kg, 95% CI -3.84, -0.60, P = .007) were associated with weight loss, whereas olanzapine (2.71 kg, 95% CI 1.87, 3.55, P < .001), and clozapine (2.80 kg, 95% CI 0.26, 5.34, P = .03) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.
Conclusions:
Switching antipsychotics to agents with lower weight gain potential, notably to aripiprazole and ziprasidone, can improve weight profile and other cardiometabolic outcomes. When choosing switch agents, both the weight gain potential of the pre- and post-switch antipsychotic must be considered. Antipsychotic switching in psychiatrically stable patients must be weighed against the risk of psychiatric worsening.
Insights
Switching antipsychotics to aripiprazole or ziprasidone can reduce weight and improve metabolic health in patients with severe mental illness. Consider the weight gain potential of both current and new antipsychotics when switching.
Area of Science:
- Psychiatry
- Pharmacology
- Metabolic Health
Background:
- Patients with severe mental illness often experience obesity and adverse metabolic outcomes.
- Antipsychotic medications can contribute to cardiometabolic burden, but evidence on switching to mitigate this is unclear.
Purpose of the Study:
- To meta-analyze the effects of switching antipsychotics on weight and metabolic parameters.
- To identify specific antipsychotics associated with weight loss or gain when switched.
Main Methods:
- A systematic search of PubMed, Embase, PsycINFO, and Cochrane databases was conducted.
- Meta-analyses compared weight and metabolic changes in patients switching antipsychotics versus those staying on their current medication.
- Both across-group and before-to-after switch analyses were performed.
Main Results:
- Switching to aripiprazole significantly reduced weight and improved glucose and triglycerides. Olanzapine significantly increased weight.
- Aripiprazole and ziprasidone were associated with weight loss when switched in before-to-after analyses.
- Olanzapine and clozapine were associated with weight gain; no significant changes were seen with amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.
Conclusions:
- Switching to antipsychotics with lower weight gain potential, such as aripiprazole and ziprasidone, can improve cardiometabolic outcomes.
- The choice of switch agent should consider the weight gain profiles of both the pre- and post-switch antipsychotics.
- Antipsychotic switching in stable patients requires careful consideration of potential psychiatric risks.
Related Concept Videos
01:23Antidepressant Drugs: MAOIs and Other Agents
01:26Psychosis: Goals of Pharmacotherapy
01:28Psychosis and Antipsychotic Drugs: Overview
01:21Antipsychotic Drugs: Typical and Atypical Agents
01:28Drug Therapy
Antianxiety Medications
01:21Antipsychotic Drugs: Therapeutic Uses and Side Effects
Despite these side effects, antipsychotics are used therapeutically for various purposes, including managing schizophrenia, preventing nausea and vomiting, curbing...