Olanzapine effectively treats
schizophrenia and bipolar I disorder (BD-I); however, its use is limited by the risk of significant
weight gain and metabolic effects. OLZ/SAM, a combination of
olanzapine and
samidorphan, was recently approved in the United States for the treatment of adults with
schizophrenia or BD-I. OLZ/SAM provides the efficacy of
olanzapine while mitigating
olanzapine-associated
weight gain through
opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data characterizing pharmacokinetics,
antipsychotic efficacy, weight mitigation efficacy, safety, and long-term treatment effects. In an acute exacerbation of
schizophrenia, OLZ/SAM and
olanzapine provided similar symptom improvements versus placebo at week 4. In stable outpatients with
schizophrenia, OLZ/SAM treatment resulted in significantly less
weight gain, reducing the risk for clinically significant
weight gain and waist circumference increases of ≥5 cm by half, compared with
olanzapine at week 24. Based on open-label extension studies, OLZ/SAM is safe and well tolerated for up to 3.5 years of treatment, while maintaining
schizophrenia symptom control and stabilizing weight. The
olanzapine component of OLZ/SAM was bioequivalent to branded
olanzapine (
Zyprexa); adjunctive OLZ/SAM had no clinically significant effects on
lithium or
valproate pharmacokinetics. Additionally, OLZ/SAM had no clinically relevant effect on electrocardiogram parameters in a dedicated thorough QT study. Overall, safety and tolerability findings from clinical studies with OLZ/SAM indicate a similar safety profile to that of
olanzapine, with the exception of less
weight gain. As OLZ/SAM contains the
opioid antagonist samidorphan, it is contraindicated in patients using
opioids and in those undergoing acute
opioid withdrawal. Clinical trial results from more than 1600 subjects support the use of OLZ/SAM as a new treatment option for patients with
schizophrenia or BD-I.