H. Hunt, K. Donaldson, Mark Strem
Aug 6, 2021
Citations
0
Influential Citations
5
Citations
Quality indicators
Journal
Journal of Clinical Psychopharmacology
Abstract
Abstract Purpose Antipsychotic medications, including olanzapine, are associated with substantial weight gain and metabolic disturbances. We sought to determine whether coadministration of miricorilant, a selective glucocorticoid receptor modulator, with olanzapine can ameliorate these effects. Methods Sixty-six healthy men were enrolled in a 2-week, randomized, double-blind, placebo-controlled trial. The primary objective was to evaluate changes in body weight after 14 days coadministration of olanzapine (10 mg) + miricorilant (600 mg) compared with olanzapine (10 mg) + placebo. Secondary objectives included evaluating (a) the safety and tolerability of the combination; (b) the effects of the combination on glucose, insulin, insulin resistance, and triglycerides; and (c) the impact of the combination on hepatic enzymes. Results Subjects administered olanzapine + miricorilant gained less weight than subjects administered olanzapine + placebo (mean weight gain on day 15, 3.91 kg vs 4.98 kg; difference between groups, −1.07 kg; 95% confidence interval, −1.94 to −0.19; P = 0.017]). Compared with the placebo group, coadministration of miricorilant with olanzapine was associated with smaller increases in insulin (difference, −3.74 mIU/L; P = 0.007), homeostatic model assessment of insulin resistance (difference, −0.47; P = 0.007), triglycerides (difference, −0.29 mmol/L; P = 0.057), aspartate aminotransferase (difference, −32.24 IU/L; P = 0.009), and alanine aminotransferase (difference, −49.99 IU/L; P = 0.030). Conclusions Miricorilant may provide a promising option for ameliorating the detrimental effects of olanzapine, and investigation of this medication in patients affected by antipsychotic-induced weight gain is warranted. Two phase 2 studies of miricorilant in patients with recent and long-standing antipsychotic-induced weight gain are currently in progress.