Olanzapine/Samidorphan Combo Found to Reduce Antipsychotic-Induced Weight Gain

Patients with schizophrenia taking the antipsychotic olanzapine in combination with the opioid-receptor drug samidorphan gained less weight and had smaller waistline increases than patients taking olanzapine alone, according to a study published in AJP in Advance. In addition, the combination drug was as effective as olanzapine alone at improving schizophrenia symptoms and had a similar safety profile.

This study was sponsored by Alkermes, maker of samidorphan.

Cristoph Correll, M.D., of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and colleagues randomly assigned 561 adult patients with schizophrenia to receive 24 weeks of olanzapine/samidorphan (10mg/10mg daily in week 1, 20 mg/10 mg daily afterward) or olanzapine (10mg daily in week one, 20 mg daily afterwards). All the participants had a body mass index between 18 and 30 at baseline and reported weight stability of at least three months.

After 24 weeks, the average medication-induced weight gain was 4.21% in the olanzapine/samidorphan group and 6.59% in the olanzapine group, respectively. “Not only were patients less likely to gain any weight with combined olanzapine/samidorphan, but also the risk of clinically significant weight gain (of ≥7% and of ≥10%) was reduced by 50% relative to olanzapine,” the authors wrote.

Patients taking the combination therapy also had smaller increases in waistline circumference after 24 weeks compared with those taking olanzapine alone (2.36 cm vs. 4.47 cm). “Waist circumference is a proxy for central fat accumulation, and increases in waist circumference have been associated with a greater risk of cardiovascular disease and diabetes, even independently of weight,” the authors wrote.

Despite the differences between the two groups in weight gain and waist circumference, there was no difference between the groups in measures of triglycerides, cholesterol, glucose, and insulin.

“Initial weight gain has still been observed with combined olanzapine/samidorphan over the first four to six weeks, and this must be factored into any benefit-risk assessment,” the researchers wrote. “However, by mitigating weight gain after this initial period and reducing the number of patients who have substantial increases in weight and waist circumference, combined olanzapine/samidorphan mitigates one of the key safety risks of olanzapine that has limited its clinical use.”

For related information, see the Psychiatric News article “SGAs Increase Teens’ Abdominal Fat, Decrease Insulin Sensitivity.”

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