Olanzapine and samidorphan combo mitigates antipsychotic-associated weight gain in psychiatric illness

The researchers found that the odds of clinically significant weight gain at the ≥ 10% and ≥ 7% thresholds were reduced by 36% and 39%, respectively, with OLZ/SAM versus olanzapine. The findings were published in The Journal of Clinical Psychiatry on March 22, 2023.

Patients with early-phase bipolar I disorder or schizophrenia are at greater risk for antipsychotic-associated weight gain. René S. Kahn, Icahn School of Medicine at Mount Sinai, New York, New York, and colleagues evaluated the weight gain effects of the combination of olanzapine and samidorphan versus olanzapine in early-phase illness in the ENLIGHTEN-Early, a 12-week, randomized, double-blind study conducted between June 2017 and December 2021.

The study included 428 young adults (16–39 years) with DSM-5 schizophrenia, bipolar I disorder, or schizophreniform disorder, < 4 years since symptom onset, BMI < 30 kg/m2, and cumulative antipsychotic exposure of < 24 weeks. They were randomized to OLZ/SAM (5–20/10 mg/d) or olanzapine (5–20 mg/d).

The primary endpoint was determined as a per cent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, Clinical Global Impressions-Severity (CGI-S) change, and waist circumference change.

The authors reported the following findings:

• Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed.
• Per cent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% versus 6.77%; least-squares mean [LSM] [SE] difference, −1.87%).
• Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% versus 30.4%, respectively; OR = 0.64); hierarchical testing precluded further statistical evaluation of secondary endpoints.
• Proportions of patients with ≥ 7% weight gain (33.1% versus 44.8%; OR = 0.61) and waist circumference change (2.99 versus 3.90 cm; LSM [SE] difference, −0.92 cm) favoured OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was −0.82.
• OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes.

"In patients with an early course of their illness, and thus at high risk for weight gain, OLZ/SAM resulted in less weight gain at week 12 compared with olanzapine while providing similar antipsychotic efficacy," the researchers wrote.

Small metabolic changes observed in both the OLZ/SAM and olanzapine groups were consistent with previously reported early olanzapine effects on glucose and lipid metabolism.

"Taken together with previously published findings, these data indicate that OLZ/SAM mitigates olanzapine-associated weight gain across both early and later stages of illness," they concluded.

Reference:

Kahn RS, Kane JM, Correll CU, et al. Olanzapine/samidorphan in young adults with schizophrenia, schizophreniform disorder, or bipolar I disorder who are early in their illness: results of the randomized, controlled ENLIGHTEN-Early study. J Clin Psychiatry. 2023;84(3):22m14674.