In this video, Christoph U. Correll, MD, discusses the possible clinical applications of the combination of olanzapine and the mu-opioid antagonist samidorphan. Dr. Correll is Professor of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
The olanzapine/samidorphan combination, also known as ALKS 3831, is being evaluated by the US Food and Drug Administration. Alkermes is seeking approval of the investigational drug for the treatment of both schizophrenia and bipolar disorder. A study on ALKS 3831, which Dr. Correll co-authored, was presented at Psych Congress 2019.
Read the transcript:
The question then is, where would this medication, which is likely to be approved by the Food and Drug Administration in 2020, where would it sit clinically? Olanzapine plus samidorphan reduced weight gain compared to olanzapine, and in a separate Phase 3 study that the FDA required, there was similar efficacy in acutely exacerbated patients versus placebo.
We could say yes, this combination, olanzapine plus samidorphan, has the same efficacy as olanzapine, but less weight gain. Whether or not there is also less metabolic burden, future studies will show.
Clinicians who would reach for olanzapine would now have a treatment option that basically has less weight gain, and also it had less waist circumference elevation, which means that also there might be less central adiposity, which in the long run could predict less cardiometabolic burden.
Would clinicians, family members, and patients say, "If I need something like olanzapine, of that strength in terms of efficacy, why put up with more weight gain?" Most likely, patients might be treated with olanzapine plus samidorphan more often, particularly if you can see early on that patients gain a lot of weight with olanzapine proper.
To what degree clinicians might use olanzapine plus samidorphan instead of other antipsychotics that have less weight gain than olanzapine proper, that will have to be shown, and might also depend on shared decision‑making and the risk/benefit ratio of each of those medications.
There was one other finding that's interesting to maybe then consider in the real‑world application, that for the first 6 weeks, olanzapine plus samidorphan and olanzapine were tracking each other almost similarly, but after that, the curve, the shape of weight gain actually leveled off with olanzapine plus samidorphan.
In the real world, maybe over the long haul, there is not so much more weight gain than would be seen with other, less weight gain‑producing drugs that at least acutely have less weight gain, but might catch up in the long run.