J Psychopharmacol. 2006 Jan 9; [Epub ahead of print]
Naltrexone and buprenorphine combination in the treatment of opioid dependence. Gerra G, Fantoma A, Zaimovic A.
Dear Colleagues,
Out of 60 trial patients given rapid detoxification using naltrexone, 34 (57%) completed a 12 week follow-up. These researchers state that due to 'very poor' compliance with oral naltrexone for relapse prevention, they decided to add buprenorphine to the naltrexone. Half of the sixty were given the buprenorphine (4mg daily) in addition to naltrexone 50mg daily. Three month retention was almost double in the experimental group at 73% versus 40% in the pure naltrexone patients, which was highly significant statistically.
The authors propound their theory that adding these drugs leaves kappa opioid receptor antagonism as the major medication effect. This may be a simplistic view, being "on-off" logic, as it ignores the variable absorption of both drugs, different receptor affinity and other unknown factors including the degree of partial antagonism of buprenorphine on mu and/or kappa receptors. While it is said to be this speculation which led to the trial, it may be more productive to speculate on the actual outcomes of this most unusual clinical study.
It appears that buprenorphine is able to breach the block of naltrexone at certain dose levels. This would explain why more patients continued in treatment when it included buprenorphine. [It may also explain the reported large black market in buprenorphine in Perth, WA.]
The conclusion seems contradictory: "The combination of buprenorphine and naltrexone may significantly improve the outcome of opioid antagonists treatment in terms of retention, negative urinalyses, and reduced dysphoria, mood symptoms and craving."
Gerra wrote up a successful report of oral naltrexone over ten years ago. His very positive abstinence outcomes were never replicated by the many similar trials since then.
I cannot see the benefit in trying to compare a treatment which is known from many trials to be relatively ineffective (oral naltrexone for relapse prevention has very low retention rates) with an experimental one. Here, buprenorphine is from the very class of drugs being avoided in this population seeking abstinence. The results are therefore almost meaningless, except to show yet again that oral naltrexone has limited results following rapid detoxification.
My conclusion is that there is now abundant evidence that oral prescribed naltrexone has little if any benefit in opioid addiction treatment in unselected patients. This may be why enthusiasts are currently treating patients with unlicensed naltrexone implants, a practice which should only be done, in my view, under controlled trial conditions with ethics approvals and appropriate funding.
