The Future of Schizophrenia Treatment

Although there have been significant advancements in the treatment of schizophrenia, it is estimated that 10-30% of people with schizophrenia are resistant to current treatments or experience adverse side effects from the treatments themselves. Patients who are resistant to treatment continue to suffer a lower quality of life, and scientists are therefore continuing to pursue new treatment alternatives. The following are a few drugs and therapies that are actively being studied for use in treating schizophrenia.

ALKS 3831 (Alkermes)

ALKS 3831 is a two-component medication involving samidorphan, a mu opioid receptor antagonist, and olanzapine. This combination is being considered because samidorphan is capable of mitigating the side effects that olanzapine can incur, such as weight gain and adverse metabolic consequences such as decreased insulin sensitivity/impaired glucose tolerance. However, samidorphan does not interfere with olanzapine's antipsychotic effects, which makes samidorphan an attractive drug to be combined with olanzapine when treating schizophrenia patients.

Structure of samidorphan

Phase 2 of an ALKS 3831 study was completed in January 2015, and it demonstrated positive results in two key areas. Alkermes was just as effective as olanzapine alone at reducing the scores of the Positive and Negative Syndrome Scale (PANSS),  a scale that is used to determine how severe a particular case of schizophrenia is. Even more exciting was the fact that participants treated with Alkermes experienced a mean of 51% lower weight gain after 12 weeks than those who were given olanzapine alone. Because of this, Alkermes was able to move to phase 3 trials, and in November 2019 Alkermes submitted a new drug application for ALKS 3831 to the U.S. FDA to treat Schizophrenia.

NaBen (Sodium Benzoate)

NaBen is a D-amino acid oxidase inhibitor. NaBen has been shown to improve the function of the glutamate-NMDA receptor by preventing D-amino oxidase from degrading D-serine, a key regulator of NMDA receptor activity. This drug first began to be administered to patients in 2011 as a therapy for those with schizophrenia experiencing refractory disease, or a continuation of moderate to severe symptoms even after administration of other therapies. In 2014, NaBen won the designation of being an additional treatment for schizophrenia patients. It was able to move into phase 2 trials, which showed that patients experience a mean decrease of 21% in their PANSS scores compared to a placebo. The drug began moving into phase 3 in 2016, and participants are still in the process of being recruited.

Diagram of D-amino oxidase degrading D-serine to Beta-hydroxypyruvate.

Fellner C. (2017). New Schizophrenia Treatments Address Unmet Clinical Needs. P & T: a peer-reviewed journal for formulary management, 42(2), 130-134.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265239/


Thomas K, Saadabadi A. Olanzapine. [Updated 2020 Mar 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
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MacKay Mary-Anne B., Kravtsenyuk Maryana, Thomas Rejish, Mitchell Nicholas D., Dursun Serdar M., Baker Glen B. (2019). D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression? Frontiers in Psychiatry (10), 25. https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00025/full


http://www.syneurx.com/en/snd13/

Structure of samidorphan

https://www.prnewswire.com/news-releases/alkermes-submits-new-drug-application-to-us-food-and-drug-administration-for-alks-3831-for-treatment-of-schizophrenia-and-bipolar-i-disorder-300960407.html