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Major Depressive Disorder (MDD) is a condition that affects approximately 12% of the population [1] and recurs at a rate between 50-85% regardless of treatment [2]. Treatment resistant depression (TRD) is considered if patients do not show alleviation of depressive symptoms after at least two trials of antidepressants from different pharmacologic classes [3]. Current antidepressant therapies which modulate serotonin, norepinephrine, and dopamine are based on the monoamine hypothesis, but the mechanism of MDD is now known to be more complex [4]. More aggressive treatment options including ketamine infusions, deep brain stimulation, and magnetic seizure therapy [5, 6] have also been applied in attempts to influence the unknown areas of our understanding of depression. Opiates have been known to influence feelings of depression since the 1950s. Previous studies have identified potential antidepressant effects of buprenorphine. Buprenorphine is a special type of opiate medication that is a partial agonist at the mu receptors, an antagonist at the kappa receptors and has affinity for the delta receptors, all potential modulators of mood. Recent data by Falcon et al. suggests the Kappa opioid receptors are a key player mediating the effects of BPN in tests sensitive to antidepressant drugs in mice [7]. The introduction of opioids with mixed agonist-antagonist with reduced dependence and abuse profiles has made possible the reevaluation of opioids for depression [8]. Buprenorphine has a low side-effect profile and is safe for use in the elderly and patients with renal dysfunction [9]. Buprenorphine alone has the risk of abuse like other opiates, but this can be prevented by the addition of naloxone in combination.

Off Label Use of Suboxone for Treatment Resistant Depression