Olanzapine plus samidorphan tied to less weight gain in schizophrenia

Treatment with the combination of olanzapine and samidorphan results in significantly less weight gain and smaller increases in waist circumference compared with olanzapine alone, results of a phase III study have shown. In addition, the combination treatment is well tolerated, and its antipsychotic efficacy is comparable to that of olanzapine monotherapy.

A total of 561 adults with schizophrenia aged 18–55 years were randomized to receive either combination treatment (n=280) or olanzapine monotherapy (n=281) for 24 weeks. Of these, 538 had at least one postbaseline weight assessment.

The least squares mean percent weight change from baseline to week 24 was 4.21 percent and 6.59 percent in the combination treatment and olanzapine monotherapy groups, respectively. The difference of –2.38 percent was deemed significant.

Considerably fewer patients in the combination treatment group than those in the olanzapine monotherapy group had weight gain ≥10 percent (17.8 percent vs 29.8 percent; number needed to treat [NNT], 7.29; odds ratio [OR], 0.50) and weight gain ≥7 percent (27.5 percent vs 42.7 percent; NNT, 6.29; OR, 0.50). Increases in waist circumference were similar between the two treatment groups, as was schizophrenia symptom improvement.

Adverse events in ≥10 percent of the combination treatment and olanzapine monotherapy groups were as follows: weight gain (24.8 percent and 36.2 percent, respectively), somnolence (21.2 percent and 18.1 percent), dry mouth (12.8 percent and 8.0 percent), and increased appetite (10.9 percent and 12.3 percent). Moreover, metabolic changes were small and similar between groups.

“A combination of olanzapine and the opioid receptor antagonist samidorphan is under development for the treatment of schizophrenia and bipolar I disorder,” the authors said. “The single-tablet combination treatment is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain.”