The short answer is that it is like very other drug and there was always the potential for a problem. Any practicing physician realizes that when a drug is approved by the FDA for general release to the public there are all kinds of unintended consequences that are possible. That is the basis of post marketing surveillance by the FDA. There is invariably a lot of hype associated with the release of a drug, but as I have previously pointed out the FDAs approval process is not in place to guarantee a drug that is safe for everyone. It is focused on a releasing a drug that is a potential tool for responsible practitioners. That means any drug can potentially cause a small number of serious unexpected reactions (liver failure, cardiac arrhythmia) that even the most experienced practitioners will not be able to predict. There is also an implicit understanding that the practitioners prescribing the drug have a thorough understanding of its pharmacology, indications and contraindications. Many practitioners advise against trying out a product that has just been released but that advice is tempered by the severity of individual circumstances and the hope of relief and also the general bias that new drugs are somehow better than the old ones. That bias has been repeatedly disproven.
Suboxone prescribers have to take a special course in order to get a prescriber number in addition to their usual DEA number. I took the Suboxone prescriber course about 7 years ago. It was a total of 8 hours of lectures given in a convention center room in a hotel. It was jointly sponsored by state medical association. The morning sessions were largely a review of the pharmacology of the drug and the scope of the opioid addiction problem at the time. The afternoon session focused on vignettes of patients with addictions of varying complexities and the exercise was to determine of Suboxone should be prescribed to that person and how the induction would be done. That was the first suggestion that something was problematic. There apparently were no contraindications to Suboxone. The clear message was that it should be given to anyone with an opioid addiction no matter what their social circumstances or comorbid psychiatric diagnoses and addictions. There was a definite implication that this was a drug that would revolutionize the treatment of opioid addiction.
Suboxone is a combination of buprenorphine and naloxone. Buprenorphine is the active ingredient in terms of treating addiction. In this post I will use Suboxone and buprenorphine interchangeably. The pharmacological properties of buprenorphine that were interesting in terms of potential use for addiction included the fact that it was a opioid mu receptor partial agonist and antagonist at the kappa receptor. The partial agonist effects relevant for addiction such as euphoria and sedation occur at the lower doses and the antagonist effects occur at higher doses. The antagonist effects like preventing respiratory depression were thought to put a ceiling effect on this side effects and make it safer than pure mu receptor agonists that would produce dose related toxicities. In the Suboxone course the mixed agonist/antagonist effects were described as producing less toxicity and less risk of abuse. The naloxone component of Suboxone is a pure mu receptor antagonist. In the course I took, the explanation for the combination of buprenorphine and naloxone was that it reduced the risk of intravenous drug use and that this had occurred in Europe and it resulted in several deaths. The company also sold Subutex which was buprenorphine only and indicated for use in pregnant women.
The pharmacodynamics and pharmacokinetics in real life can differ quite a bit from the idealized cases that the initial marketing and advertising was based upon. Like many medications it can be a life changing drug. People can recover and break the cycle of addiction, recovery and relapse and go on to productive lives. It is the outliers that physicians need to be most concerned about. In real life there are always going to be people who get significant side effects even at low doses and cannot tolerate the drug. There are also people who tolerate the drug at high doses and do not experience the ceiling effect of mu receptor antagonism. The people are probably very low in number but they are significant because they are not protected by the ceiling effect that is supposed to be there from the drug. Drug addiction always attracts or produces a significant number of people who become amateur pharmacologists and use the drug to facilitate their addiction. The word gets out and suddenly buprenorphine has street value (about $1,000 for a 1 month prescription) and opioid addicts can use it when they run out of heroin or oxycodone. In a few people it is their preferred opioid because it has a longer half life.
The politics of Suboxone are as complicated as you will find in the pharmaceutical industry. There are plenty of conflicts of interest in terms of how the drug was initially marketed and plenty of crossover between regulators and the company who developed, marketed and sold it - Reckitt-Benckiser. According to a New York Times article last fall, the company was granted a period of exclusive sales that ended in 2009. After that they went on the offensive to suggest that their new product - a Suboxone film was superior to the generic tablets especially in the area of child safety. They stopped selling the Suboxone tablets at that point. Insurance companies can work any controversy to their advantage and people on buprenorphine maintenance have been cut off based solely on the amount of time they have been taking the drug. There are no scientific guidelines for how long a person should take buprenorphine and like most drugs used for maintenance therapy there will never be a study that looks at that question due to the expense. Most experts would agree that if you have a severe addiction and have recovered based on buprenorphine there is no reason why you would be cut off. In fact discontinuing buprenorphine seems to present a more significant problem as dose is tapered to 2 mg and lower. We also have a familiar political theme in the issue of opioids with the government seeming to create the problems in the first place and now saying: "Trust us we have the solution." That may have explained the desperation in the descriptions of how public health officials were trying to increase Suboxone prescribers to address a public health opioid epidemic that was a likely result of government initiatives to improve the treatment of pain.
Suboxone has become a problem for the same reason that every other drug becomes a problem - unrealistic expectations, conflicts of interest, and a knowledge deficit on the part of the practitioners. The title of the New York Times article illustrates how the press can look at the dual nature of drugs and imply that there is a larger problem. I don't know of two many drugs that do not have a "Dark Side". The negative trends in buprenorphine use can be reversed but it will take more than the suggested strategy in the NY Times article. Here are a few ideas:
1. The CDC needs to get involved and look at Suboxone/buprenorphine related deaths and study it in the same manner that they studied methadone. It would be very instructive to see exactly where Suboxone/buprenorphine falls on the spectrum of deaths/100 kg MME (milligram morphine equivalents). The expectation of some in the article is that it is much safer, I would prefer to see the numbers. Only the CDC has access to the detailed data to look at this issue. I would take it a step farther and suggest that the CDC recalculate this table on an annual basis as a key metric in reversing the significant public health problem of accidental opioid overdose deaths.
2. The physicians prescribing the buprenorphine need to be highly motivated and well versed in prescribing medications to individuals with addictions. The NY Times article suggests that there are many who take an entrepreneurial approach to the prescription of buprenorphine with cash only practices that vary from $100 - $250 a visit. I have no problem with cash only practices if there is a quality approach. By definition that involves a lot more than handing someone a prescription in 5 minutes. The problem is the rest of what happens during that time is poorly defined. The original prescribing information said that the physician needed to refer the patient to counseling services. In many presentations of research that I have seen there is a clear movement to illustrate that - counseling adds little to nothing to outcomes when buprenorphine is prescribed. There are problems drawing that conclusion about this research given the modest outcomes of the buprenorphine treatment.
3. At least part of the interview of any patient recovering from the severe addiction that occurs with opioids is assessing their functional capacity. What are they doing on a day to day basis and is that routine consistent with both recovery and a lack of cognitive side effects from the buprenorphine? Being able to corroborate that improvement with a third party makes it even more reliable.
4. A big part of the unconscious aspects of addiction is the behaviors that are present to continue the addiction despite the best conscious efforts of the person affected. Good examples include craving, lying, and hiding use from others. That requires prescribing physicians to engage their patients at this level and not develop a law enforcement transference. A lot of physicians don't know how to respond to an accusation of: "You don't trust me!" when there is a question of the need for a toxicology screen or a discussion of a positive toxicology. The interpersonal aspect of treatment is very important and it received no attention in the standard Suboxone prescribing course.
5. Continued work on a model of treatment looking at all of the potential positive factors is needed. There is nothing worse in medicine than to treat a scientific topic like a political one and not have a rational approach to the person with the problem. Like the original course I took, there are people out there who say that buprenorphine prescribed out of a physicians office is all that is needed. Is that the case when you have a person who takes two to three times the prescribed amount to get high? Or the person who is crushing it and snorting or injecting it? Or the person who is selling it on the street to get purchase heroin? Or the person who can't function due to cognitive problems at 2 mg a day? Or the person who is hospitalized for recurrent bowel obstructions due to severe constipation? As the prescribing physician - are you confident that you can accurately screen for these problems? What about competing approaches like the long acting mu antagonist naltrexone injections? Where does 12-step recovery like Narcotics Anonymous fit in? Where do sober housing and residential treatment fit in? And finally - where can a person get detoxified and should anyone be forced to go through acute opioid withdrawal when they are incarcerated?
All of these questions are currently unanswered. But like most treatments in medicine, the solution is typically a lot more than a pill. Drugs with addictive potential always add the complication of significant financial gain from a captive audience.
George Dawson, MD, DFAPA
Deborah Sontag. Addiction Treatment With A Dark Side. New York Times. November 16, 2013.
SAMHSA. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. A Treatment Improvement Protocol. TIP 40.
NICE. Naltrexone for the management of opioid dependence. 2010.
NICE. Methadone and buprenorphine for the management of opioid dependence. 2010.