Combination Therapy May Reduce Weight Gain in Young Adults With Serious Mental Illness

According to research published in The Journal of Clinical Psychiatry, treating young adults diagnosed with early stages of primary schizophrenia, schizophreniform disorder, or bipolar disorder I with combination therapy consisting of olanzapine and samidorphan (OLZ/SAM; Lybalvi; Alkermes, Dublin, Ireland) resulted in less weight gain than treatment with olanzapine (OLZ) monotherapy. After 12 weeks of treatment, individuals treated with the drug combination had an overall lower body weight change compared with those treated with OLZ  only (4.91% change in body weight from baseline with OLZ/SAM and 6.77% change in body weight with OLZ according to least-squares means analysis); were less likely to experience > 7% body weight change (33.1% in this category with OLZ/SAM treatment vs 44.8% with OLZ treatment); and were less likely to experience gains in waist circumference compared with those treated with olanzapine monotherapy (increases of 2.99 cm with OLZ/SAM vs 3.90 cm with OLZ). The two medication regimens had similar safety profiles and similar antipsychotic efficacy results.  

The ENLIGHTEN-Early study (NCT03187769) was a phase 3 multicenter, randomized, double-blind study that took place over 12 weeks from June 8, 2017, to December 1, 2021, at 62 sites in 11 countries. Young adults (18-40 y) were 1:1 assigned to receive OLZ/SAM (5–20/10 mg/d) or OLZ (5–20 mg/d) for 12 weeks. The primary endpoint was the percentage change in weight at baseline and 12 weeks. Participants were tapered off their current antipsychotic medication or mood stabilizers within 14 days of randomization. Assessments of body weight, waist circumference, and body composition were made at weeks 1, 2, 4, 6, 8, 10, and 12. Additional details about the study, including exclusion and inclusion criteria, are available in the published article available online.

According to study lead author, Rene Kahn, MD, PhD, Icahn School of Medicine at Mt. Sinai, "The results from the ENLIGHTEN-Early study provide important data for clinicians treating patients early in disease and contribute to our understanding of LYBALVI as a treatment option for adult patients with schizophrenia or bipolar I disorder."