Monday, May 9, 2011

Opioids for Treatment Resistant Depression?

My colleague, Mark Rose, recently submitted this post about the potential use of buprenorphine as an antidepressant treatment for treatment resistant depression. To our knowledge, no further studies of this have been done. Perhaps it's time?


Buprenorphine may be effective in treatment-refractory depression

Mark E. Rose, MA
Licensed Psychologist

Persons with major depressive disorder (MDD) are considered treatment-refractory (TRD) when they fail to respond to multiple trials of antidepressant medication from different classes (Keller 2005). TRD is a devastating condition that results in substantial health care and economic cost, and untold suffering to the patient and family members (Nierenberg et al. 2007). Most FDA-approved antidepressant drugs act through monoamine reuptake inhibition, and medications that act through alternate mechanisms need to be available to patients with unrelenting depression that is untreatable with conventional antidepressants. The results of a study published 15 years ago hint that a currently available drug may provide greater benefit to patients with TRD than any other known pharmaceutical agent.

Although opioids were used to treat MDD until the late 1950s, research evaluating their antidepressant potential has been very rare in the past 60 years (Berrocoso et al. 2009). The synthetic opioid buprenorphine is a partial mu receptor agonist and kappa receptor antagonist, is exceptionally safe in overdose, and produces substantially less euphoria than pure mu receptor agonists such as morphine and oxycodone. A small study (Bodkin et al. 1995) evaluated the therapeutic potential of buprenorphine in the treatment of TRD. The 10 study participants averaged a 20.7–year duration of unipolar major depression, 7.6 previous unsuccessful antidepressant trials, and a HAM-D score of 28.1. Buprenorphine was initiated in open-label manner at 0.15 mg/d with maximum upward titration to 1.80 mg/d over the 4-6 week trial (final mean dose 1.26 mg/d). Three subjects dropped out due to malaise, nausea, and dysphoria. Of the remaining 7 subjects, 6 achieved marked clinical improvement. The mean endpoint HAM-D score was 10.7, a 60.7% reduction from baseline, and 4 patients achieved complete remission (HAM-D ≤ 6). The mean overall level of functioning increased 45.5% and mean subjective depression rating decreased 50%. Significant improvement became apparent at the end of week 1.

The authors conclude that the results are remarkable, with the number of previous treatment failures, the level of disease severity, and the duration of improvement arguing against placebo effect as the basis of treatment response. Patients did not report euphoria or intoxication but instead felt ‘more normal’, which together with the 33% drop-out suggest limited abuse liability in persons with TRD. These results are literally begging for replication, but sadly, despite awareness of this data for 15 years, researchers have not conducted follow-up studies due to the stigma surrounding opioid drugs and their association with addiction.

Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry. 2005;66(Suppl 8):5-12.

Nierenberg AA, Katz J, Fava M. A critical overview of the pharmacologic
management of treatment-resistant depression. Psychiatr Clin North Am. 2007;30(1):13-29.

Berrocoso E, et al. Opiates as antidepressants. Current Pharmaceutical Design. 2009;15:1612-1622.

Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995;15:49-57.


  1. Most people don't understand or believe you when you tell them that if you have severe/refractory depression how much relief you get from certain opiate meds(oxycodone)seems to be the one that works the best for me.Drs. really need to start looking at this as a real treatment for refractory depression.

  2. I discovered this effect by accident. I was in a car accident and had a neck injury. I'm not a candidate for surgery, so I was referred to a pain clinic. I have always suffered from depression, and not only did my medication (percocet) help with my neck pain, it also lifted the depression I had been battling for a long time. Yes, people can become dependent or addicted to this medication, but it is sad that so many people suffer needlessly because of the stigma surrounding it. As always, if something works, they will find a way not to give it to people.

  3. I m so happy that I ve come across this information, I really thought I was the only one who felt this way in using opiates for severe refractory depression. My daughter has suffered such severe depression since she was 10years old, she's now 22 years old. She's been hospitalized on numerous occasions in the past, and has many suicidel thoughts. She was precribed oppiates for pain one time and low and behold she came around like a beautiful blooming flower, it was simply amazing ...I saw something that I've never seen since she was a young child. She said she finally felt normal and happy and she couldn't remember the last time she felt this way. She also suffers from extreme social anxiety and all this went away while she was taking this drug too. Now it's to convince the doctors and this is where it gets hard, we are now in the middle of trying to convince the doctor what she really needs ..this works and we must have it or who knows what will happen to my young beautiful daughter.