Naltrexone and Buprenorphine at the Same Time -An Up and Coming Protocol  
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Any one who knows me knows that I am always trying to get my patients opiate free.  While some people will require long term maintenance, others can get free of opiates after a temporary period of discomfort which lasts from weeks to months.  I have found that the longer one spends on the Buprenorphine, the longer and more difficult this period of discomfort is. 

Patients taking Naltrexone do better than those who do not.  Even recently, a study done by Dr. Kleber at Columbia University demonstrates that people on Naltrexone do well even when they receive the Naltrexone in a once monthly injection.  I have always wondered why patients do better. 

One reason might be that Naltrexone antagonizes kappa opiate activity.  Kappa activity has been shown to cause psychological distress.  If someone is on Naltrexone, they have less kappa activity and less distress.  However, the trick is getting them on Naltrexone.

Up until recently, I have waited 5-7 days after weaning a patient of Buprenorphine prior to starting the Naltrexone.  This has been problematic.  Patients feel psychological distress and seek more Suboxone.  Or worse, they relapse with their drug of choice.  Those patients who have been on buprenorphine longer have more difficulty than those who have been on it for shorter times.

I have always asked myself the question: is this distress related to their prior use of their opiate of choice or their more recent use of buprenorphine.  Recent research indicates that the use of buprenorphine itself  may be causing the distress seen during the weaning of buprenorphine.  Buprenorphine blocks kappa activity.  When kappa activity is blocked, the kappa receptors up-regulate.  This likely causes increased kappa activity upon discontinuation of the drug and psychological distress. 

Since Naltrexone also blocks kappa activity, it may minimize the distress seen with Buprenorphine discontinuation.   Recently, a study looking at buprenorphine and naltrexone at the same time was published.  In fact there are about 5 studies of this that I have found over the last 10 years.  Patients were started on buprenorphine and within a few days naltrexone was added.  Patients felt well and 70% stayed with the program until the end.  70% is as good an outcome as we ever see in drug treatment.  There was very little withdrawal seen when the naltrexone was begun.  Other studies have seen some minor withdrawal at the onset of naltrexone.  

The authors of these studies focused on kappa blockade as the mechanism of action underlying the success of this treatment.  They felt that the naltrexone blocked Buprenorphine at the mu opiate receptor.  This left additive effects on kappa blockade at the most likely mechanism of action for the improved sense of well being.   

I have begun to use my own version of this protocol in my office.  After patients have been stabilized on Suboxone around a dose of 4-8 mgs, I begin a schedule of daily naltrexone.  Patients are started on 1 mg/day and are increased to 50 mgs over the course of about one week.  The buprenorphine weaning continues.  It is possible that there may be some more intense withdrawal symptoms this way but many patients do feel better.  They are also fully blocked from the effect of any potential drug relapse that may occur. 

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Stuart Wasser M.D.
April 23, 2006