Samidorphan/Olanzapine Combination Proves Effective in Treatment of Schizophrenia


Investigators also report that the therapy could mimic the efficacy of olanzapine but cancelled out the medication-induced weight gain, improving symptoms and outcomes.

Samidorphan and olanzapine (Lybalvi) as a combination treatment for schizophrenia proved to have successful outcomes and was generally well tolerated by individuals, according to the results of a study published in Annals of Medicine and Surgery.

Investigators also reported that samidorphan could mimic the efficacy of olanzapine but cancelled out the medication-induced weight gain, which shows promise for improving symptoms and health outcomes in individuals with schizophrenia.

Investigators searched Google Scholar and PubMed to find clinical trials that proved efficacy with a Positive and Negative Syndrome Scales (PANSS) score, Clinical Global Impression-Severity (CGI-S) score, and weight changes, safety, with ECG parameters, movement disorders, and suicides, and adverse outcomes of the drugs as a combined regimen.

After removing duplicate articles and screening abstracts, 12 articles were included on the shortlist, and 4 were further excluded after investigators reviewed the full text of the articles.

In the 8 articles included, there were 4 phase 3 trials, 2 phase 2, and 2 phase 1, with a total of 2231 randomized individuals.

Investigators reported that 5 trials used CGI-S and PANSS scales to access the efficacy of the combination.

Overall, the combination showed a significant reduction in both scores and can be considered for long-term treatment, they said.

In 1 article, there were no significant differences in weight changes for the combination and olanzapine monotherapy groups. In another, the proportion of weight change decreased by about 37% in the combination group compared with olanzapine plus the placebo.

Additionally, in the same study, individuals in the olanzapine group had a 2.7 times greater risk of gaining greater than 10% of their body weight from baseline.

Another trial demonstrated the same outcomes of the stability of weight changes in the combination group from 6 weeks and onwards, while the individuals in the olanzapine monotherapy group continued to gain weight.

For safety, investigators assessed the outcomes in 6 different trials. In 3 of the studies, ECG parameters were used to evaluate the tolerance of the combination regimen. In 5 trials, investigators used the Columbia-Suicide Severity Rating Scale to assess suicidal behavior and ideations in individuals.

Additionally, akathisia, dyskinesia, and parkinsonism were evaluated by 3 trials.

Overall, the investigators determined that the safety of the drug combination was well established, and individuals were tolerant to the combination.

They determined that individuals exhibited various adverse effects, including suicidal ideation and weight gain but the efficacy outweighed the risk.

Investigators acknowledged that the review has limitations.

For example, the clinical trials that were included had a considerable number of individuals who withdrew, because of adverse event or lack of efficacy, which caused missing data. Additionally, 3 of the 8 trials showed a high risk of bias, which stemmed from insufficient information about randomization or lack of it.

The drug combination of samidorphan and olanzapine is an FDA-approved drug recombination for the treatment of individuals with schizophrenia.


Rehan ST, Siddiqui AH, Khan Z, Imran L, et al. Samidorphan/olanzapine combination therapy for schizophrenia: efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials. Ann Med Surg (Lond). 2022;79:104115. doi:10.1016/j.amsu.2022.104115

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