Killing the Suboxone Gift Horse with Naltrexone

First Posted 11/14/2013

I received an email update today with important news from the world of psychiatry and addiction.  The email highlighted a study from the October issue of Jama Psychiatry, entitled ‘A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers’.  The study compared relapse rates in opioid addicts who were tapered off buprenorphine at different rates.  The study considered success as being free of opioid use and taking naltrexone, an orally-active opioid antagonist, after 12 weeks.  The study found that 50% of the people tapered off buprenorphine over 4 weeks were abstinent and taking naltrexone.  That compared to 21% and 17% of success in patients tapered over 1 or 2 weeks, respectively.

I’m sorry, but who cares?

Regular readers of my blog know my opinion about buprenorphine.  (Newcomers please note that by buprenorphine I mean buprenorphine, Suboxone, or Zubsolv, since they all work in identical fashion).  Most people who work in the addiction field agree that addiction is a life-long illness.  Most people who have worked in the field for a few years or more know that relapse is a common feature of opioid dependence.  I believe that anyone claiming to ‘cure’ opioid dependence through use of a plant, root, amino acid, vitamin, hypnosis, accu-pressure point, or 90-day program is either misinformed, pathologically optimistic, lying, or blinded by profit motives.

Opioid dependence is associated with a high rate of death and morbidity. Beyond buprenorphine, the only reliable intervention for treating opioid dependence is methadone maintenance, if ‘reliable’ is defined as ‘likely to be successful.’  I realize there are hundreds if not thousands of residential treatment facilities throughout the US that advertise ‘freedom from addiction’; some even offering freedom from ‘addiction’ to buprenorphine.  These claims are made, and apparently believed, even with one-year relapse rates greater than 90% in opioid addicts treated without medication.  In the real world of ‘Suboxone Talk Zone’, I have to burst a few bubbles about ‘sending someone to treatment.’    For opioid dependence, treatment without medication yields long-term sobriety in only a small minority of patients.
Yet many healthcare professionals continue to chase after the golden goose of abstinent recovery.  Makes me wonder if laetrile would still be around with better marketing!

Before buprenorphine, opioid dependence was an oft-fatal illness that in most people responded only to the administration of opioid agonists at frequent intervals, with no patient autonomy and the threat of discharge if anything prevented on-time arrival at the early-morning line-up.  In 2003, along came buprenorphine— a prescription medication with a reasonable generic cost (finally), with few or no long-term risks and tolerable side effects, that eliminates cravings and prevents illicit opioid use in 50% of an average study population of opioid addicts who are allowed to continue their medication.  So why, exactly, are we excited by the prospect of changing from buprenorphine to a medication that carries the risk of hepatic necrosis?

Are people on naltrexone better off than people taking buprenorphine?  One would hope so, given that 50%-83% of people in the current study went back to active using while trying to make the switch!  Patients on naltrexone still have the problem of blocked mu receptors during emergency surgery.  Having blocked opioid receptors is an even larger problem for many educated addicts than their doctors realize, that goes something like this: ‘I stopped opioid agonists, but now I have to block my endorphins too?!
Why not just keep stable buprenorphine patients on buprenorphine?

The argument for naltrexone over buprenorphine comes down to two issues.  The first is the quasi-spiritual attitude that people are in an inferior form of treatment if their mu receptors are bound by even a partial agonist—no matter that those receptors have developed complete tolerance to the agonist effects of the drug.

The second argument focuses on diversion.  Buprenorphine is sold on the street, particularly in areas where there are no doctors certified to prescribe the medication.  People divert buprenorphine in a number of ways, ranging from efforts to get high, to use ‘in between’, to attempts at self-treatment.  But should risk of diversion reduce the legitimate use of a medication that has saved thousands of lives? Is it logical to throw the bupe-baby out with the bath water when deaths from buprenorphine are less common than deaths from acetaminophen?

I expect that the risk of diversion decreases over time in patients treated with buprenorphine.  Patients in long-term, stable treatment are more likely  employed and insured, with less financial incentive to sell controlled substances and more to lose for doing so.  Most of my stable patients develop insight into the damage caused by addiction, and have no interest in getting someone else caught in the same trap.  Most of the patients I’ve treated over time have severed their connections with the using world.  And most of them are grateful for a second (or tenth) chance at life; grateful enough to avoid risking everything by selling drugs.

Even if diversion could be blamed, in part, on stable buprenorphine patients, why is addiction treated differently than other diseases?  Diversion of opioid agonists is a greater problem than diversion of buprenorphine, both by sheer volume and by the damage from diversion, yet the FDA just approved another potent mu agonist in Zohydro—a drug with far greater diversion potential than buprenorphine or Suboxone.  If diversion doesn’t disqualify the pain meds used for strained backs, bumps, and bruises, why should diversion derail one of the only effective treatments for a disease that is killing thousands of young people?  Heck, pseudoephedrine is sold from pharmacies with a signature; the dangers of methamphetamine didn’t eliminate our collective concern for people with stuffy noses!

If we take diversion out of the argument—for example by deciding that the 300-odd deaths from buprenorphine diversion don’t warrant removing an effective treatment for a disease that has become the leading cause of death in young adults— the push off buprenorphine makes little sense.  I suspect that the people advocating ‘progressing’ from buprenorphine to naltrexone do not envision patients treated indefinitely with naltrexone either, but rather see naltrexone patients as somehow ‘closer’ to abstinence than buprenorphine patients.  From a neurochemical standpoint, what is the difference between being fully tolerant to a partial agonist vs. taking an antagonist?  For relapse-prevention, advantage goes to buprenorphine, since ‘effective relapse’ to opioid agonists requires buprenorphine patients to first go through days of withdrawal.  Naltrexone patients on the other hand can miss the morning’s naltrexone, and later that night relapse using mu receptors that are even hyper-sensitive to agonists.

As for arguments that patients on buprenorphine are impaired, I would love to see my attorney-patients take part in THAT debate.  Concerns of impairment have come from poorly designed studies where buprenorphine groups consisted of patients with no tolerance to the medication. I suspect that medical reporters too often read the abstract and skim the ‘materials and methods’—let alone the statistics!
If ‘success’ consists of moving to naltrexone—a medication that many real-world addicts reject–   how long is naltrexone continued, and what happens when it is stopped?  Do people go back to heroin again?  If not, why not? The cycle of ‘use, treat, cease treatment, use, and repeat’ should be a black box warning on naltrexone— as soon as they finish stamping the warning on the steps of every residential treatment center.

I’ve been accused of being too long-winded.  The short version for those who skipped to the bottom:  buprenorphine-based medications offer an effective, tolerable, long-term treatment for a chronic, life-long disorder.  How many people will die in their quest—or their doctor’s quest—for ‘abstinent recovery’ with or without naltrexone?  Emphasis on naltrexone is just one more example of looking the gift horse of buprenorphine treatment in the mouth.

Sigmon SC, Dunn KE, Saulsgiver K, Patrick ME, Badger GJ, Heil SH, et al. A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers. JAMA Psychiatry. Oct 23 2013;