Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine

Death by suicide is a global epidemic with over 800 K suicidal deaths worlwide in 2012. Suicide is the 10th leading cause of death among Americans and more than 44 K people died by suicide in 2019 in the United States. Patients with chronic pain, including, but not limited to, those with substance use disorders, are particularly vulnerable. Chronic pain patients have twice the risk of death by suicide compared to those without pain, and 50% of chronic pain patients report that they have considered suicide at some point due to their pain. The kappa opioid system is implicated in negative mood states including dysphoria, depression, and anxiety, and recent evidence shows that chronic pain increases the function of this system in limbic brain regions important for affect and motivation. Additionally, dynorphin, the endogenous ligand that activates the kappa opioid receptor is increased in the caudate putamen of human suicide victims. A potential treatment for reducing suicidal ideation and suicidal attempts is buprenorphine. Buprenorphine, a partial mu opioid agonist with kappa opioid antagonist properties, reduced suicidal ideation in chronic pain patients with and without an opioid use disorder. This review will highlight the clinical and preclinical evidence to support the use of buprenorphine in mitigating pain-induced negative affective states and suicidal thoughts, where these effects are at least partially mediated via its kappa antagonist properties.