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Opioidergic Agents as Antidepressants: Rationale and Promise

Abstract

Research concerning psychiatric issues relating to opioid drugs currently focuses primarily on their role in reinforcing addictive behaviors, given the recent proliferation of lethal abuse of illicit opiates in the United States and around the world. In contrast, this article will review the mechanism of action of opioids in affective disorders and the available evidence and potential for their use, especially in the treatment of resistant major depression. Buprenorphine is the opioid derivative of special interest; we review this and other opioid derivatives, highlighting the growing role of opioids in treating depressive illnesses and other related psychopathologies.

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Notes

  1. Samidorphan combined with buprenorphine differs from naloxone combined with buprenorphine, as naloxone is not absorbed sublingually, and leaves buprenorphine’s μ-activity unaffected when administered sublingually. Naloxone is intended to prevent illicit administration of buprenorphine parenterally, as parenteral naloxone blocks μ-activity.

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Correspondence to Parnika P. Saxena.

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Conflict of Interest

Parnika Saxena has no conflicts of interest to declare. J. Alexander Bodkin has a potential conflict due to longstanding efforts to advance the development of buprenorphine as an effective treatment for resistant depressive illness. He has helped Alkermes to engage in a development program of a buprenorphine/samidorphan preparation for use as an adjunctive treatment for resistant depression. This guidance was provided gratis; however, compensation was provided for participation in annual day-long group meetings with a group of academics held by Alkermes in Boston. His lab was also provided with funding for their work on a study on the long-term safety and efficacy of Alkermes’s buprenorphine/samidorphan preparation. Dr Bodkin will not benefit financially if the Alkermes preparation is approved and marketed, nor will he be harmed financially if it is not approved. Dr Bodkin authored one of the first American studies of buprenorphine in depression in 1995 and is one of the leading experts in the US on the use of opioids in depressive illness. He has assessed legal cases over the years as an expert on behalf of psychiatrists facing regulatory or civil litigation for having used opioids in treating resistant depression.

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No sources of funding were used to assist with the preparation of this review.

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Saxena, P.P., Bodkin, J.A. Opioidergic Agents as Antidepressants: Rationale and Promise. CNS Drugs 33, 9–16 (2019). https://doi.org/10.1007/s40263-018-0584-7

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