Buprenorphine: prospective novel therapy for depression and PTSD

Psychol Med. 2020 Apr;50(6):881-893. doi: 10.1017/S0033291720000525. Epub 2020 Mar 24.


Background: Depression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.

Method: Bibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.

Results: Original clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.

Conclusions: Pharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

Keywords: Chronic pain; opioid use disorders (OUD); post-traumatic stress disorder (PTSD); suicidal ideation; treatment-resistant depression (TRD).

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid / therapeutic use*
  • Antidepressive Agents / therapeutic use
  • Buprenorphine / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naltrexone / analogs & derivatives
  • Naltrexone / therapeutic use
  • Prospective Studies
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Young Adult


  • ALKS 5461
  • Analgesics, Opioid
  • Antidepressive Agents
  • Drug Combinations
  • Buprenorphine
  • Naltrexone