Antipsychotics vary in weight gain and metabolic side effects in Schizophrenic patients through treatment courses

A new study found that the type of metabolic side effects varied among various antipsychotics in mid to long-term treatment. They differed in weight gain and metabolic parameters during treatment. The study results were published in the journal World Psychiatry. 

Antipsychotics are the main line of management for schizophrenia. They are efficacious in preventing acute episodes. But metabolic side effects of antipsychotic drugs may increase mortality due to their serious health consequences. As most patients with schizophrenia take these medicines for a long duration, it is necessary to understand the metabolic side effects of the various schizophrenic drugs. Angelika Burschinski et al conducted a network meta-analysis of various randomized control trials to evaluate the mid-to-long-term metabolic side effects of 31 antipsychotics in persons with schizophrenia.

The study was carried out by applying the random-effects Bayesian network meta-analysis and searching databases like the Cochrane Schizophrenia Group's Study-Based Register of Trials and PubMed. Published and unpublished, open and blinded randomized controlled trials with a study duration >13 weeks which compared any antipsychotic in any form of administration with another antipsychotic or with a placebo in participants diagnosed with schizophrenia were included in the analysis. Weight gain as measured in kilograms was the primary outcome. Secondary outcomes included “number of participants with weight gain”, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. 

Key findings of the study: 

• 137 eligible trials with 35,007 participants on 31 antipsychotics, with a median follow-up of 45 weeks were included in the study. 
• Chlorpromazine (mean difference to placebo: 5.13 kg), followed by clozapine (4.21 kg), olanzapine (3.82 kg), and zotepine (3.87 kg) produced the most weight gain. 
• There was no substantial change in the findings in sensitivity and network meta-regression analyses, although enriched design, drug company sponsorship, and the use of observed cases modified the mean difference in weight gain to some extent instead of intention-to-treat data.
• Antipsychotics that caused more weight gain were often the drugs with worse outcomes in fasting glucose and lipid parameters.
• The confidence in the evidence ranged from low to moderate. 

This is the first study to analyze the metabolic side effects of antipsychotic drugs in mid to long-term treatment. These metabolic side effects should be considered while prescribing the drugs as schizophrenia is often a chronic disorder.  

Further reading: Burschinski A, Schneider-Thoma J, Chiocchia V, et al. Metabolic side effects in persons with schizophrenia during mid- to long-term treatment with antipsychotics: a network meta-analysis of randomized controlled trials. World Psychiatry. 2023;22(1):116-128. doi: 10.1002/wps.21036