In this video, Christoph U. Correll, MD, discusses the results of the ENLIGHTEN‑2 study, which compared weight gain and cardiometabolic side effects in patients taking olanzapine and patients taking olanzapine plus 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 poster on the research, which Dr. Correll co-authored, was presented at Psych Congress 2019.
Read the transcript:
Olanzapine is considered one of the most effective antipsychotics, but its use has been really complicated by a lot of weight gain and metabolic abnormalities. We know that cardiometabolic side effects can lead to life‑shortening events like cardiovascular events, hypertension, diabetes, and related myocardial infarction, stroke. So, the medication use of olanzapine has been reduced.
The question was, can you retain the efficacy of olanzapine, but somehow clean up the cardiometabolic burden? The addition of samidorphan, which is a mu‑opioid antagonist to olanzapine, was one option to try out because in healthy controls and in a phase 2b study, there was a reduction in weight gain compared to olanzapine alone.
This study now, the ENLIGHTEN‑2 study, was a 6‑month study that compared olanzapine alone or plus placebo vs. olanzapine with samidorphan, trying to see whether over 6 months the weight gain would be less and also, secondarily, the cardiometabolic side effects.
The primary outcome was percent weight change. The co‑primary outcome was the proportion of patients gaining at least 10%. The key secondary outcome was at least 7% of weight gain.
What did this study show? It showed that there was a significant benefit of lower weight gain with the olanzapine plus samidorphan combination. It was only 4.2% vs. 6.6% weight gain with olanzapine proper.
Also, the proportion of patients gaining at least 10% was 18% with olanzapine plus samidorphan versus 30%, which is a 12% difference, and the number needed to treat of 8 or 9. Even on the key secondary outcome, 7% weight gain, again, the combination of the mu‑opioid antagonist plus olanzapine beat olanzapine alone.
There was not a significant difference in glucose and lipid metabolism, but what was somewhat surprising in this study was that overall, in these patients aged 18 to 55 that were studied for 6 months, there was relatively less weight gain on olanzapine alone than expected or seen in another studies.
Also, there was very little metabolic change in lipids and glucose, so that the combination of olanzapine plus samidorphan had less power to actually separate from olanzapine alone.