Buprenorphine and Its Therapeutic Potential in Psychiatric Disorders


Researchers discuss new research on buprenorphine, the “gold standard” treatment for opioid use disorder at the APA Annual Meeting.




*A note from the authors: When we first presented our study at the APA annual meeting, we only had preliminary results. Now that our investigation is complete, the results are presented in this article.

Buprenorphine, along with methadone and extended-release naltrexone, is 1 of 3 medications currently approved by the US Food and Drug Administration (FDA) to treat opioid use disorder (OUD). Buprenorphine is considered the “gold standard” treatment for OUD and has been proven to reduce mortality and to improve treatment retention and remission. Buprenorphine has an advantage over methadone in that it has a lower overdose risk due to its ceiling effect and is less likely to cause QTc prolongation.

Opioid receptors have been extensively studied for the treatment of opioid addiction, but recent research has shifted to investigating opioid receptors in the treatment of psychiatric conditions. A significant proportion of patients with an OUD also have cooccurring psychiatric conditions. There is growing evidence from neurobiological research that the endogenous opioid system is involved in mood regulation and that disturbance of this system may lead to depression and anxiety, making it a potential therapeutic target for the treatment of these ailments.

Our study’s goal was to analyze clinical studies in order to determine the efficacy of buprenorphine in treating psychiatric conditions, in particular depression and suicidality (Figure).

Figure. Buprenorphine and Its Therapeutic Potentials in Psychiatric Disorders, Presented at the American Psychiatric Association 2022 Annual Meeting

Figure. Buprenorphine and Its Therapeutic Potentials in Psychiatric Disorders, Presented at the American Psychiatric Association 2022 Annual Meeting

We conducted a literature search in 5 major databases, including PubMed, using inclusion and exclusion criteria. Of the 1347 identified studies, 6 clinical trials were included in this meta-analysis pooling in 417 adult participants. First, HAM-D inter-group assessment favored buprenorphine use compared to control (Cohen’s d=-0.34, 95% CI=-0.66, -0.02, P=0.04). Second, MADRS scores found endline (mean score changes compared to baseline) shifts of depression scores were in favor of buprenorphine (Cohen’s d=-0.31, 95% CI=-0.61, -0.01, P=0.04). Third, BSSI favored the use of buprenorphine (Cohen’s d=-1.4, 95% CI=-0.61, -0.01), and in the intra-group analysis, a single dose (64 mg) of sublingual buprenorphine was superior to 96 mg (Cohen’s d=0.19) and 32 mg (Cohen’s d=-0.22) single doses.

Several hypotheses have been proposed as to the mechanism of action of buprenorphine in the treatment of psychiatric disorders. The review of study shows that buprenorphine has an antidepressant effect at doses ranging from 2 to 8 mg/day, as well as an antisuicidal effect at relatively low doses (0.1 mg to 0.44 mg). According to several studies, buprenorphine's antisuicidal effect may be due to a partial agonist effect on the μ-opioid receptor and an antagonist effect on the delta and κ-opioid receptor. One plausible explanation for buprenorphine's antisuicidal effect is its potential to reduce the psychological or physical pain processing. Also, because of its agonism of nociceptive receptors, it may have anti-anxiety properties, too, and anxiety is an independent risk for suicidality.

Concluding Thoughts

A growing body of literature indicates that buprenorphine has therapeutic potential in treating psychiatric conditions, mainly via the endogenous opioid system. The findings of this study show that buprenorphine has a promising role in reducing depression and suicidality. Lower dosages appear to be more effective in producing favorable psychiatric outcomes in terms of decreasing suicidality.

Despite growing evidence in favor of buprenorphine in the treatment of psychiatric conditions, there are issues to consider before prescribing such as diversion and the potential for abuse. Larger and more rigorous studies are required to establish the efficacy of buprenorphine in psychiatric conditions or to widely use it in clinical practice.

Dr Ahmed is an addiction psychiatrist; diplomate of the American Board of Psychiatry and Neurology; and medical director of the West Ridge Center for Addiction Recovery at Rutland Regional Medical Center in Rutland, Vermont. Dr Bhivandkar is the chief resident at the St. Elizabeth Boston psychiatry residency program and a co-investigator for this study.

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