Olanzapine-Samidorphan for Schizophrenia: New Real-World Adherence Data

Christoph Correll, MD, presented efficacy and real-world data on olanzapine-samidorphan for schizophrenia and bipolar disorder.

Correll described samidorphan as a mu-opioid receptor-preferring opioid antagonist that modulates appetite and satiety signaling.¹ When combined with olanzapine in a single pill, samidorphan attenuates but does not reverse the weight gain associated with olanzapine, with the effect emerging after about approximately 4 weeks.² He characterized the combination as preserving olanzapine's established efficacy while reducing its cardiometabolic burden.

On efficacy beyond positive symptoms, Correll addressed the longstanding challenge of negative symptoms in schizophrenia, noting that conventional antipsychotics produce secondary improvements in negative symptoms as positive symptoms resolve—a phenomenon he described as pseudo-specificity. To isolate a more specific signal, researchers analyzed subgroups with both prominent positive and negative symptoms, and separately those with predominant negative symptoms and relatively few positive symptoms. Reductions of approximately 8 to 9 points on the negative symptom subscale of the Positive and Negative Syndrome Scale were observed in both subgroups, suggesting a degree of specificity. He framed negative symptom improvement as clinically consequential: "as you improve negative symptoms we would assume and have also shown data in other studies that there's more engagement with social life with maybe work and school and having a fuller ability to reach not just symptom reduction but also recovery."

Real-world data reinforced the randomized controlled trial findings. A mirror-image analysis demonstrated that patients starting olanzapine-samidorphan showed significant reductions in emergency department visits and hospitalizations over 6 months compared to the prior 6 months. A matched cohort analysis further showed superior treatment adherence and longer duration on medication compared to other antipsychotics (including olanzapine monotherapy) in both schizophrenia and bipolar disorder populations.

Dr Correll is professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra Northwell in New York and professor and chair of child and adolescent psychiatry at Charité University in Berlin, Germany.

References

1. Chaudhary AMD, Khan MF, Dhillon SS, et al. A review of samidorphan: a novel opioid antagonist. Cureus. 2019;11(7):e5139.

2. Grywińska WB, Głowacka A. Combining samidorphan with olanzapine to mitigate weight gain as a side effect in schizophrenia treatment. Postep Psychiatr Neurol. 2023;32(3):128-137.