When it comes to the risk of metabolic side effects, not all antipsychotics are equal, suggests a meta-analysis published in World Psychiatry. The analysis revealed that patients with schizophrenia who took chlorpromazine or clozapine for more than 13 weeks experienced the most weight gain on average compared with those taking placebo. Angelika Burschinski, M.D., of the Technical University of Munich and colleagues compiled data from 137 clinical trials that compared outcomes of patients who had schizophrenia, schizophreniform disorder, or schizoaffective disorder and took antipsychotics or placebo for more than 13 weeks. The combined sample included 35,007 participants who had taken 31 different antipsychotics (both oral and injectable) that are available in the United States and/or Europe. The researchers compared the effects of these medications on body weight as well as fasting glucose, cholesterol, and triglyceride levels. The median age of the participants in the analysis was 39 years, and the median length of follow-up was 45 weeks. The researchers found that five antipsychotics contributed to significant average weight gain relative to placebo:

• chlorpromazine (5.13 kg, or over 11.3 lbs)
• clozapine (4.21 kg, or over 9.3 lbs)
• zotepine (3.87 kg, or 8.5 lbs)
• oral olanzapine (3.82 kg, or 8.4 lbs)
• long-acting injectable olanzapine (3.60 kg, or 7.9 lbs)

Seven other antipsychotics, including risperidone and quetiapine, were associated with average weight gains of 1 to 2 kg (2 to 4.5 lbs) over the study period. The medications associated with the highest weight gain in participants were also associated with greater changes in glucose, cholesterol, and triglyceride levels. Olanzapine was associated with the greatest effects on glucose, total cholesterol, and LDL cholesterol; amisulpride (which led to an average weight gain of 1.43 kg, or over 3 lbs), was associated with the greatest effects on HDL cholesterol and triglycerides. [M]etabolic side effects of antipsychotics are likely to contribute to the average 14.5 years reduced lifespan of individuals with schizophrenia. Furthermore, weight gain is associated with decreased quality of life and treatment nonadherence, the latter resulting in poor treatment outcome and  relapses,” Burschinski and colleagues wrote. “As antipsychotic drugs are often taken for long periods of time, our results represent more valuable clinical information on these health consequences than previous analyses based on short-term studies, which on average only lasted 6 weeks.” (SOURCE: January 23, 2023 APA Psychiatric News Alert)