It is well established that a common side effect of second-generation antipsychotics is weight gain, which can influence a patient’s attitude toward the treatment and reduce adherence, worsening symptoms and quality of life. A meta-analysis in Schizophrenia Bulletin suggests that switching patients with serious mental illness who are taking one or more antipsychotics to aripiprazole or ziprasidone may lead to weight loss and other cardiometabolic improvements.
Dan Siskind, M.B.B.S., M.P.H., Ph.D., of Metro South Addiction and Mental Health Service in Brisbane, Australia, and colleagues combed through the scientific literature for studies of people with serious mental illness that investigated a switch from any single or combination of antipsychotics to a different antipsychotic monotherapy for ≥4 weeks. Only studies that reported an endpoint and/or mean change for cardiometabolic parameters, including weight, body mass index (BMI), waist circumference, cholesterol, and blood glucose levels, were included in the meta-analysis.
In total, the authors analyzed 61 articles, which described studies of 8,554 people (mean age, 39 years)—the majority of whom had been diagnosed with schizophrenia or schizoaffective disorder, bipolar disorder, or comorbid mental disorders. Most of the studies provided observational data on the outcomes of interest before and after a switch to a specific antipsychotic. Ten studies, however, had data on switching to a new antipsychotic versus staying on the previous agent. The mean duration of the studies included in the meta-analysis was 26 weeks.
Siskind and colleagues noted that meta-analyses of switch-versus-stay were possible only for aripiprazole and olanzapine. In contrast, before-to-after meta-analyses were conducted for the following antipsychotics: aripiprazole, amisulpride, clozapine, lurasidone, olanzapine, paliperidone/risperidone, quetiapine, and ziprasidone.
In the switch-versus-stay meta-analyses, only aripiprazole significantly reduced weight (−5.52 kg), while olanzapine significantly increased weight (2.46 kg). Switching to aripiprazole also significantly improved fasting glucose (−3.99 mg/dl) and triglycerides (−31.03 mg/dl). 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) and ziprasidone (−2.22 kg) were associated with weight loss, whereas olanzapine (2.71 kg) and clozapine (2.80 kg) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.
“Although switching to a different antipsychotic, notably aripiprazole and ziprasidone, may lead to weight loss, these benefits must be weighed against any potential risks of adverse drug reactions or deterioration in psychotic symptoms,” Siskind and colleagues cautioned. “[S]witching antipsychotics in psychiatrically stable patients may risk relapse and detrimental consequences for at least some patients.” They added that antipsychotic switching is only one of several interventions that might help reduce weight and improve cardiometabolic parameters in patients with serious mental illness. Other interventions include lifestyle counseling and exercise.
For related information, see the American Journal of Psychiatry article “How Much of an Advance Is the Addition of Samidorphan to Olanzapine?”
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