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Updated: Jan 6, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
The Potential Clinical Use of Opioid-Receptor-Modulating Drugs in Bipolar Disorder
Maria Gefke1,2, Christina B Wagner3, Roger S McIntyre4
1The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Psychiatric Centre North Zealand, Copenhagen University Hospital-Mental Health Services CPH, Dyrehavevej 48, Hilleroed, 3400, Copenhagen, Denmark. maria.gefke@regionh.dk.
None:
Treatment resistance in bipolar disorder (BD) is common, and innovative treatments are needed. The opioid system is under investigation as a new target treatment of depression and BD, notably the treatment of depressive symptoms. This narrative review aims to synthesize the evidence related to opioid-receptor-modulating drugs in treating BD. The protocol was preregistered at Open Science Framework. A search of the literature databases Embase, PubMed, and PsycINFO was conducted in March 2024 for studies involving the treatment of manic or depressive symptoms of BD with an opioid-receptor-modulating drug. The studies revealed a preliminary antimanic but transient effect of intravenous naloxone and potential antimanic effects of pentazocine. Methadone showed an effect on regulating manic symptoms. The existing evidence on the effects of opioid-receptor-modulating drugs in BD is scarce, and most studies are older and based on small samples. Clinically, opioid-receptor-modulating drugs cannot be recommended or integrated into the treatment of BD. Still, well-designed, randomized controlled trials are needed to draw any firm conclusions.
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