Is a glucocorticoid antagonist a potential treatment alternative for antipsychotic-induced weight gain?

Objective: To evaluate the efficacy and safety of mifepristone as a new treatment modality for antipsychotic-induced weight gain. Methods: We searched databases up to March 2021, for the published English-language literature including a Medical Subject Heading 'Mifepristone,' 'Receptors, Glucocorticoid,' 'Weight gain,' 'Overweight,' 'Obesity,' 'Body Weight Change,' 'Antipsychotics Agents,' 'Glucocorticoid Receptor Blocker,' 'Glucocorticoid Receptor antagonist.' We identified two clinical and four preclinical studies utilizing mifepristone as a treatment modality. Results: The results of the olanzapine clinical trial showed that mean increase in weight from baseline to day 14 was greater in the olanzapine with the placebo group (3.2 ± 0.9 kg) than the olanzapine with mifepristone group (2.0 ± 1.2 kg) and the mifepristone with placebo (2.0 ± 0.7 kg), and a similar effect was observed in the risperidone with mifepristone clinical trial. Conclusions: Mifepristone shows potential in the management of AIWG. Glucocorticoid antagonists can be a viable alternative to curb this side effect. Large-scale clinical studies are warranted to determine the medication's safety and efficacy based on this mechanism of action.