NALTREXONE(VIVITROL)- is it too optimistic to call it a cure?
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There is a medication called naltrexone that that I feel is extremely important to optimize chances for long-term abstinence.  There is no question in my  mind that this is the most underused intervention in the field of addiction medicine.

 So what does it do? The medication had traditionally been considered only an opioid blocker.  It was designed to prevent someone addicted to heroin or pain medication from getting high.  The medication would presumably sit in mu opioid receptor without stimulating it.  However, it does not let heroin and/or pain medication from interacting with the receptor.  This creates a chemical wall between the bloodstream and the brain.  Therefore, the addict would not feel anything even if they used their drugs.   The clinical result would be that their drug use would go down. 

 The reality is that naltrexone does so much more than that.  In addition to having a blocking effect, the medication seems to have other effects that reduce craving for opioids.  This reduction in cravings is the main reason I use it.  The mechanisms for accomplishing the reduction is not 100% agreed upon but I believe I have several insights into what they might be.

 At the simplest level, the knowledge that the person can't get high may reduce craving.  Why use if you can't get high?  Maybe this is the only reason it works but I believe there is much more to it.   

Naltrexone clearly affects the time course of the post-acute withdrawal syndrome.  Post-acute withdrawal syndrome consists of long term irritability, cravings, depression and insomnia.  It likely represents low-grade withdrawal and it is probably contributed to by persistent physiologic imbalances that make the brain less sensitive to its own endorphins.  This can take from several months to up to a year to resolve.  The use of naltrexone accelerates the resolution of these imbalances and people feel better within a week or two.

The drug does this by sensitizing the brain to the naturally occurring endorphins.  Naltrexone has classically been considered just a blocker so it has been difficult to understand how this would work.  However, recent research over the past few years show the drug works as an INVERSE AGONIST.   In order to understand this means, one must first understand that the opioid receptors have a baseline activity even when not stimulated.  It is as if there is an idling speed (which is significantly increased during early withdrawal) and will be active even when not filled with either a drug or a natural endorphin neurotransmitter.  The naltrexone reduces this activity.   
This forced reduction in activity changes the cell in several ways.  It increases the number of available receptors and it changes the expression of a wide variety of other proteins; the cell becomes more responsive to the natural endorphins.  It will also change in the way it interacts with other cells downstream in the brain.  The whole process results in an improved state of well being much more quickly.

Some patients voice a concern that naltrexone would reduce pleasure by blocking natural pleasure chemicals; however, clinical experience shows this does not happen.  Its' action as an inverse agonist explains how naltrexone can work without having to have a major blocking effect on the natural endorphins and enkephalins.  While it is possible that these are partially blocked, millions of years of evolution have resulted in a high degree of attraction between the natural endorphins and the receptor; any block seems to be overcome.  Therefore, people do not have to overly fear the loss of pleasure from losing their own endorphins.

Another effect of Naltrexone is to block kappa receptors in the brain.  This will relieve anxiety and irritability.  Kappa receptors are a sub-class of opiate receptors.  Unlike mu receptors, which when stimulated result in euphoria and pain relief, kappa receptor stimulation will cause psychological distress.  In animal studies, when kappa receptors are blocked, there is evidence of an improved psychological state.  Naltrexone blocks kappa receptors and will therefore improve mood and reduce cravings.  In fact, this may indicate a need to continue naltrexone for several months or longer to keep cravings under control.

 There is also evidence that naltrexone's effect on blocking opioid receptors in the hypothalamus will reduce appetite.  Perhaps, the anti-craving effect of naltrexone is also related to a generalized anti-appetite effect.

Whatever the mechanisms are, patients on naltrexone clearly crave opiates less and feel better.  The effects on some patients have been striking and have mimicked the reduction of cravings seen with high doses of Suboxone.  However, with naltrexone, there is no physical dependence and the drug can be stopped at any time.  The worst problem I see with stopping the drug before 3-4 months of therapy is a reemergence of cravings- there is no physical withdrawal.  I have not see cravings emerge after 6 months of use. 

 I believe that every one should go on the medication for at least several months.  They should use it even longer if they have problems with impulse control or if they are surrounded by triggers. 

It is currently available as a pill and is used at doses that range between 50 and 100 mgs.  Although it has been usually prescribed as a once a day pill, I find it works much better at twice daily dosing.

September of 2010 saw the injectible form of naltrexone, VIVITROL made by Alkermes, receive an indication for use in opioid dependence. This has been had an astounding benefit for those using it.  It is expensive- $750/month for self pay- but most insurance companies cover it, charging a typical brand name copay which Alkermes will forgo (if you have a coupon).  It is safer, easier, and more effective than the pills, but the pills are cheaper ($100-200/month)

 There are also non-FDA approved implants which are used but data on their effectiveness is limited.

For persons who have been on opioids, there is a possibility of precipitating some degree of withdrawal at the beginning of therapy.  I usually like to wait for the fifth day following the last use of buprenorphine. (I’ll wait seven days following other opiates and 14 days following Methadone,)  The drug needs to be started slowly. 

You need to obtain a razor blade.  Cut the pill in half, than cut one half into quarters and then, one quarter into eighths.  Take one eighth.  I double the dose every day until the whole pill is taken  If withdrawal is precipitated on a given day, the same dose is repeated the following day.  Any withdrawal felt on subsequent days will be far less.

 In my office, I have specially compounded  dosages of naltrexone starting at 1 mg to make the transition onto naltrexone even easier.

 
After a patient is stable on 50 mgs., the injection can be given. 

Side effects from the medication are uncommon.  Perhaps, 10% of my patients do not tolerate the pills secondary to stomach upset.  Liver problems were seen in animals when they were given 7-8 times the equivalent dose that we currently use.  Monitoring for liver disease has become a standard of practice but I have yet to see a problem in this regard.  In fact,  the liver improves because the person is living a healthier lifestyle.  There has been a rash reported that I also have not ever seen.

 Patients also lose weight due to its ani-appetite effects especially when combined with other weight loss medications.

 The injection has almost no problems outside of injection site reactions.  The injection may have an additional benefit.  The drug levels obtained during the first week are higher than those obtained with the pills.  That results in additional efficacy in accomplishing some of the anti-craving effects discussed above.

 

Naltrexone has been especially valuable in the treatment of young adults who are still supervised by their parents.  When the medication is taken, the parent has less to worry about when their child is outside the house and a degree of trust can begin. 

I try to use naltrexone in the majority of my patients in early recovery and try to elicit the help of the family whenever possible.  As one patient aptly put it , it "REBOOTS" the brain.  It is the closest thing we have to a cure. 

I feel that this medication has been very successful in helping my patients stay sober



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Stuart Wasser MD

December 25, 2002
Revised 2/18/06, 10/28/10, 6/23/13