Not All Antipsychotics Affect Metabolic Health Equally in Schizophrenia

A systematic review and network meta-analysis published in World Psychiatry reported that antipsychotic drugs had differing impacts on metabolic outcomes among patients with schizophrenia.

Investigators from the University of Munich in Germany searched publication databases through June 2021 for studies reporting metabolic effects from antipsychotic treatments in the setting of schizophrenia. A total of 137 studies comprising 35,007 patients and 28 antipsychotic interventions were included in this analysis.

The pooled study participants had a median age of 38.9 (interquartile range [IQR], 35.3-41.4) years, and the median proportion of women was 37%.

For the outcomes of weight gain, fasting glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, no antipsychotic was significantly favored over placebo.

The antipsychotics that tended to be favored over placebo were fluspirilene long-acting injectable (LAI), haloperidol LAI, fluphenazine LAI, fluphenazine, ziprasidone, and haloperidol for weight gain (mean difference [MD] range, -9.13 to -0.01 kg); ziprasidone for fasting glucose (MD, -0.67 mg/dl); ziprasidone and aripiprazole for total cholesterol (MD range, -4.69 to -0.75 mg/dl); aripiprazole and ziprasidone for LDL-C (MD range, -1.92 to -1.32 mg/dl); aripiprazole, lurasidone, haloperidol LAI, aripiprazole LAI, paliperidone, and sertindole for HDL-C (MD range, 0.15-0.71 mg/dl); and ziprasidone, lurasidone, aripiprazole, and cariprazine for triglycerides (MD range, -13.09 to -1.07 mg/dl).

In the analysis that pooled the LAI and oral formulations of each antipsychotic, no intervention was significantly favored over placebo. The best intervention was fluspirilene, however the confidence interval was wide (MD, -7.11; 95% CI, -16.83 to 2.87 kg).

Compared with placebo, chlorpromazine, clozapine, olanzapine, zotepine, pimozide, and sertindole were associated with an average weight gain of ³2 kg. In general, the drugs that associated with the greatest weight gain also associated with poor outcomes for the other metabolic measures.

The results of this study may not be generalizable for patients who have new-onset schizophrenia, as data suggest that weight gain affects patients who are treatment-naïve to a greater extent and only 11% of this study population were naïve to antipsychotic treatment.

Analysis authors concluded, “Antipsychotics differ clearly in weight gain and metabolic parameters in mid- to long-term treatment. The magnitude of the differences in fasting glucose and lipid parameters was approximately the same as previously reported for short-term studies, suggesting that these effects occur quickly.”