Q&A: Buprenorphine for Treatment Resistant Depression?

Q: Are there any recent sources talking about the use of buprenorphine (low dose) for people who were never drug addicts or abusers but who were diagnosed with treatment resistant depression? It seems to me that if stimulants are gaining popularity in treating MDD, why wouldn't we look at low dose buprenorphine which seems to have great results anecdotally for many people with MDD.

A: Buprenorphine is an only mildly abuse-liable drug that is occasionally dramatically helpful in treating depression that does not respond to conventional treatments, even including ECT and MAOIs.

Nonetheless, there has been little work published concerning the antidepressant effects of buprenorphine in treatment refractory depression in the absence of opiate dependence since my 1995 paper. I find only one report, by Nyhuis et al in 2008, looking at low-dose sublingual buprenorphine monotherapy in 6 extremely treatment refractory hospitalized patients with a very marked response to a maximum dose of 0.8 to 2.0 mg/d for a total of 7 days of open label treatment. All but one of these subjects experienced full remission acutely.

A study of buprenorphine treatment for late life treatment resistant depression may currently be under way at the University of Pittsburgh by Dr. Jordan Karp, which is described online at Clinical Trials.gov: http://clinicaltrials.gov/ct2/show/NCT01071538. This is an open-label study, using low doses (to 1.6 mg/d) for an 8-week treatment period.

An obstacle to depression research in the US may have been the requirement that since buprenorphine’s approval in 2002 as a sublingual preparation with or without naloxone for substance abuse treatment, a special DEA number must be obtained in order to prescribe it, requiring some prior drug-abuse treatment training. This removed it from ready access for most psychiatrists who specialize in treating mood disorders.

A relevant matter of mounting scientific interest is the potential role of kappa opioid receptor antagonists in depression treatment, which has been very promising in animal models (Carlezon et al, 2009). Buprenorphine is the strongest kappa-receptor antagonist currently available for human use, although it is also a partial agonist at the mu receptor, and the relative importance of the activity at these sites is currently unknown. This may encourage further work in this area in the near future.