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Pharmacopsychiatry
DOI: 10.1055/a-2307-6484
Review

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments

Yuki Komatsu   ‡
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
2   Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
,
Moe Takehara   ‡
3   Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
,
Xenia Hart   ‡
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
4   Department of Molecular Neuroimaging, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
,
Yuna Takahashi
3   Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
,
Satoko Hori
3   Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
,
Fumihiko Ueno
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
5   Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
6   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
,
Hiroyuki Uchida
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
› Institutsangaben Funding Japan Society for the Promotion of Science — http://dx.doi.org/10.13039/501100001691; JP19H03587 and JP20K20603 Overseas Research Fellow Award This work was supported by JSPS KAKENHI, Grant Numbers JP19H03587 and JP20K20603 (H. Uchida). Dr. Hart was supported by an Overseas Research Fellow Award from the Japan Society for the Promotion of Science.
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Abstract

Introduction Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.

Methods A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.

Results Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.

Discussion Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

Keywords

antipsychotic. schizophrenia - pipeline - non-dopaminergic

‡ These authors contributed equally to this work: Yuki Komatsu, Moe Takehara, Xenia Hart




Publikationsverlauf

Eingereicht: 28. Januar 2024
Eingereicht: 30. März 2024

Angenommen: 05. April 2024

Artikel online veröffentlicht:
06. Mai 2024

© 2024. Thieme. All rights reserved.

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