The Medication Assisted Treatment (MAT) Debate

There is an understandable general reluctance in the addiction treatment community to Medication Assisted Treatment (MAT). In the past, MATs have proven to be of questionable reliability, at best, particularly since many substance abusers sought to use it as a quick fix, and did not combine it with coterminous behavioral modification. Many were simply substituting one drug for another. I’ll add that in my travels, meetings and conferences I have attended, that most treatment personnel I’ve met stand firmly against MAT. However, The US Surgeon General Report “Facing Addiction in America” (the “Report”) has further delved into this controversial area with an extensive analysis of several MATs which it describes as having clearly demonstrated proven effectiveness. MAT is therefore certainly a topic worthy of an objective, open-minded review. MATs: Lifeline…Or Crutch? I’d like to start out by pointing out what MAT is not. For example, when Naloxone (commonly commercially referred to as Narcan, among other names) is used in emergency situations to immediately counteract an opioid overdose. The use of the drug in this instance is rescue related and administered in a quick, high dosage to save someone’s life. In fact, Naloxone acts almost miraculously, when an overdose is caught in its early stages, stopping the effects of overdose in its tracks as if nothing ever occurred. However, even this manner of use is not without its detractors. Some medical professionals fear it is used as a crutch by opioid addicts who push the envelope of getting high, knowing that Naloxone can save their lives if they surpass their limits. I don’t want to wade into that debate other than to say Naloxone has saved many lives and is obviously not recommended for long-term addiction treatment. A “Behavioral Intervention” MAT, on the other hand, is intended to be administered in small doses to counteract regular drug use. The Report identified six specific MATs it claims have shown promise and they only apply to opioid and alcohol related addiction. The Report emphasizes that such treatments have proven “highly effective” when combined with “behavioral interventions”. It also points out that the purpose of the medication component is to block the euphoric and sedating effects, reduce cravings and/or mitigate the symptoms of withdrawal. The MATs identified for Opioid Use Disorder involve the drugs: (1) Methadone, (2) Buprenorphine, and (3) Naltrexone. The most important aspect of these MATs, aside from the previously mentioned use in conjunction with behavioral therapy, is that it can be faithfully maintained for a sufficient duration. Patients who receive MAT for fewer than 90 days show NO improved outcomes, and patients who receive MAT for less than 3 years are more likely to relapse than those who stay with it longer. The Methadone Question Methadone is a synthetic opioid agonist. For those of you not familiar with that term, an agonist is a chemical substance that binds to and activates certain cell receptors causing a biological response which reduces cravings. (The other type of MAT related activator is an antagonist. An antagonist stops opioids from binding to the brain’s receptors so that a patient on an antagonist just won’t get high if they take opioids. For the sake of simplicity, think of an agonist as a substitute and an antagonist as a blocker.) Methadone is the longest running MAT, having been in use for over 40 years. It has a proven track record but also many critics, because it stands out as the classic example of substituting one addiction for another. There are also concerns regarding prescribed Methadone users transferring their drugs to third parties for illicit use (called Diversion) and when methadone doses exceed recommended range, which can lead to overdose and death. Methadone programs are now called Opiate Treatment Programs and must be certified by the Substance Abuse and Mental Health Services Administration and registered with the US Drug Enforcement Administration. They’re mostly outpatient programs in which patients must initially take their doses under observation. These programs have the added benefit of limiting other diseases such as HIV and Hepatitis C, since they eliminate needle sharing so common in the heroin addiction community.

Buprenorphine and Naltrexone Buprenorphine is considered a partial agonist because it adheres to the receptors with less intensity. Clinical research indicates that it can be highly effective during the initial phases of treatment to get the substance abuser into stasis (stable non-drug detox). Also while Buprenorphine itself does not appear to pose an independent overdose threat, even if combined with opioids, it can still be deadly if combined with tranquilizers and/or alcohol. It can also be combined with low doses of Naloxone to positively tweak outcomes. It is now available in low doses, as an implant that can last up to 6 months, for patients in maintenance, to help avoid the negative effects of patients’ inadvertent failure to take their meds. Physicians are limited in the number of patients they can treat at the same time, in order to control Diversion to third parties, but as a result of the program’s effectiveness, these restrictions were eased considerably in July 2016.​ Naltrexone is an opioid antagonist, completely blocking their activation. It is therefore deemed not abusable. It completely interrupts the side effects of opioids (much like Naloxone) and can therefore lead to rapid opioid withdrawal syndrome for patients not completely out of Detox. It is often considered as a second-stage treatment option for patients formerly on Buprenorphine or Methadone who fear relapse. If they then take opioids, they won’t feel the benefit, so they won’t bother to continue. Naltrexone is available in both daily and extended release forms. One additional point I found interesting was that the report failed to take note of commonly used MATs I’ve come across in my research, such as Vivitrol and Suboxone for opioid abuse, and Antibuse disulfiram for alcohol abuse. I’m not sure why that’s the case. Perhaps the Surgeon General elected not to include the names of specific commercial products. Regardless, the report certainly covered a lot of new ground and can’t be expected to have included everything. Treating Alcohol Use with MATs There are currently three FDA approved medications for treatment of alcohol use disorder: (1) Disulfiram, (2) Naltrexone, and (3) Acamprosate. None carries risk of misuse or addiction and all are therefore not DEA scheduled substances. Disulfiram interferes with the body’s metabolism of alcohol, which leads to sickness when it is consumed. The intensity of the reaction depends on both the dose of the Disulfiram and the amount of alcohol ingested. The major impediment for this solution is adherence, because Disulfiram basically punishes consumption. One or two negative episodes tends to take the alcoholic firmly in one direction or another, in his recovery. It depends on how desperate he is for a solution. For that reason, Disulfiram is most effective when its use is supervised or observed to increase compliance. Naltrexone counteracts some of the “pleasurable” aspects of drinking in a similar fashion that it does with opioids. In fact, Naltrexone is even showing up in other sorts of addiction treatment, like obesity. It is one of the principal components of Contrave which recently began an advertising campaign for use by obesity patients trying to lose weight. Cross addiction is universally recognized as a potential issue for substance abusers in recovery. To that end, perhaps Naltrexone could actually serve a multi-purpose function by addressing the root cause of addiction; that it’s a brain disorder. Acamprosate normalizes alcohol related neurochemical changes in the brain, reducing the symptoms of cravings that can prompt a relapse. There are two main causes for relapse, the actual physical craving and the psychological euphoric recall of a pleasurable event. This is a demonstration of how a MAT combined with traditional therapy can concentrate synergistically to aid in treatment. The Emergence of Ibogaine One interesting drug that has shown potential as a MAT is not even mentioned in the Report, probably because it is still not approved for use in the United States. Ibogaine was originally utilized as an anti-depression cure from 1939-1970. Around the same time it was being phased out, a 19 year old heroin patient noticed it eliminated his cravings to use. It is derived from a rainforest shrub commonly known as Tabernanthe Iboga. News spread and heroin clinics opened around the world. Initial results were very positive with clinicians claiming it acted like an addiction reset button, but some severe side effects led to unacceptably high mortality rates during treatment. Research has continued outside the US for decades and the drugs success at lower doses (some clinics claim success rates of up to 70%) is once again opening the debate. Kratom, derived from a plant in the coffee family, commonly found in Indonesia, Malaysia and Thailand, is another controversial MAT that has also gained considerable attention as of late. Many former opioid addicts swear by it, claiming that it has saved their lives. The United States Drug Enforcement Agency recently considered classifying it as a Schedule I drug and even began doing so on an emergency basis, but in an unprecedented move, they held back as a result of tremendous political backlash. While more professional research is required in these two, and many other areas, perhaps we’ll see approval of some new and innovative MATs in the near future. Promising Research Continues Even more potentially compelling is the promise of a vaccine against opioids, reported in a December 2016 issue of The Economist. The Scripps Research Institute in La Jolla, California, claims to have developed just such a vaccine. They created a process through which opioids are made to attract the attention of the human immune system (which is normally not the case), by having them attach to a ‘carrier’ protein. That lures the immune system into creating anti-opioid antibodies. Experiments to date have been successful in mice, remaining effective for 2-4 months. While there are still many hurdles to overcome for human use, it demonstrates some of the ‘outside-the-box’ thinking that can be useful to combat addiction’s rapid growth. While the Report seems to strongly endorse the use of MATs, absolute acceptance is hardly universal. For example, on the heels of the Report, the Agency for Healthcare Research and Quality produced its own report listing dozens of MAT related questions it says require further research. Moreover, addiction is certainly much more encompassing than simply alcohol and opiates. When it comes to MATs, it seems that there are still more questions than answers. I for one, would have liked to see more information on the number of people who were treated using MATs and some specific information on success rates. I would also feel more comfortable seeing it used as a treatment of last resort, after a few relapses, once all else has failed. Moreover MATs should not be implemented on their own, without additional therapeutic treatment. While MATs limit the cravings, they do nothing for euphoric recall which can often be equally damaging. Nonetheless, considering what we’re up against, it would seem prudent to be open-minded about any process that might be effective in gaining the upper hand against addiction.

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