MAT

MAT, in the context of Addiction Medicine, is an acronym that stands for “Medication Assisted Treatment”, and I will be discussing how this applies to opioid use disorders (addiction to heroin, Dilaudid, Roxicodone, etc.). In my first article introducing the concept of MAT, I discussed two different “models” often used to explain an individual’s predilection for addiction- the “moral model” and the “disease model”. My contention, reinforced by the vast majority of experts in the field of Addiction Medicine, was that addiction is, in fact, a chronic brain disease and we should manage it as we would manage other chronic disease states such as diabetes and hypertension. This management of other chronic diseases includes the comprehensive approach of lifestyle modification and medication, when appropriate. We are already aware of the lifestyle component of addiction treatment- namely the various stages of rehabilitation, and then proceeding with 12 step work, attending meetings, etc. But, what about the medication aspect of treating this particular chronic disease? This aspect of treating addiction with medication is known as MAT.

With respect to opioid use disorder, MAT falls into two general categories: opioid agonists, and opioid antagonists. They are used at different times, and in different patient circumstances. Again, like anything in medicine, this a treatment that is individually tailored to each specific patient, and sometimes the patient is simply not a candidate for any MAT at all. In this article I would like to specifically discuss the opioid agonist group of MAT, methadone and buprenorphine products, and address the topic of opioid- antagonists in the next article.

The concept behind opioid agonist therapy is straight forward- replace the illicit substance that our patient is addicted to with a similar substance that is more controllable, but effects the brain in a similar fashion. The severe withdrawal symptoms and cravings an addict experiences upon discontinuation of an opioid are essentially due to the relatively sudden absence of the abused opioid on the addict’s brain receptors. Most often, statistically around 90% of the time, this withdrawal and/or craving is severe and uncomfortable enough that the addict relapses on his or her drug of choice. The sudden introduction of the opioid back into the addict’s body and brain brings an immediate halt to withdrawal symptoms and acute cravings.

The problem is that the opioids most addicts use have an extremely short half-life and must be used several times a day to avoid withdrawal and maintain the happiness/euphoria to which they are accustomed (a term known as “hedonic tone”, which I will explain in the future as well). Also, the chosen method of introduction into the body is typically one that offers the most immediate desired results- specifically intravenous drug use. This method of use is obviously fraught with risks, such as infectious disease transmission (HIV, hepatitis C, among others), and a drastically increased risk of overdose.

Overdose typically occurs because the addict has no idea what is actually in the “heroin” they are injecting into their veins, or how potent the substance is- it is, quite literally, a game of Russian roulette with a substantial risk of overdose and death with every single self-administration. The urine drug test results on my “heroin addicts” very commonly reflect the unknown presence of numerous substances such as cocaine, fentanyl, and most recently carfentanyl (an opioid often used as an elephant tranquilizer that is about 1000 times as potent as morphine). It is easy to see that the slightest bit too much of any of these uber-potent drugs can, and often does, result in overdose and death. This concept, and the reality of drug dealers mixing their own drug cocktails with these novel drugs (and I assure you that these drug dealers do NOT possess Louis Pasteur’s drug mixing proficiency), is the reason why “heroin overdoses” and deaths have risen to such a stratospheric level.

So, that’s the background- 90% of the time the addict picks back up because the withdrawal symptoms and/or cravings are so unbearable that they simply can’t take it any longer. Opioid agonist MAT drugs attach to the opioid receptors in the patient’s brain, and just like they would if they used their opioid of choice, the withdrawal symptoms and cravings abate. When properly prescribed, opioid agonists used for MAT reduce or eliminate drug-seeking behaviors (i.e. stealing, robbing, prostituting, needle-sharing) and do not produce a “high” or impair functioning.

I feel it is also imperative that I comment on an extremely disturbing circumstance that I routinely witness- the simultaneous prescribing of chronic opioid agonist MAT (i.e. methadone or buprenorphine/”Suboxone”) and chronic benzodiazepines in an out-patient setting. This combination can cause serious and sometimes FATAL RESPIRATORY DEPRESSION (and this risk is exponentially higher in our opioid use disorder population- if they could take things according to a prescription on a bottle they wouldn’t be addicts!). Any physician prescribing these drugs in combination is truly doing a disservice to his or her patients, and their liability in event of an adverse outcome is absolutely indefensible and unforgivable!

Methadone is the oldest example of an opioid agonist used to treat opioid addiction. As described, methadone attaches to the same opiate receptors in the brain that heroin and other opioids do, and attenuates withdrawal symptoms and reduces cravings. The downsides of methadone are that it is only available at specific government-sponsored clinics, the patient has to go to the clinic daily (at least initially) in order to receive their dose for the day, the safety profile of methadone is somewhat problematic (interactions with other drugs, a propensity to cause respiratory depression, a very real risk of overdose if too much is consumed, and cardiotoxicity and “QT prolongation”), and the patient does remain dependent on an opioid. Although methadone has certainly been used successfully for decades in the treatment of opioid use disorder, these limitations make it less desirable, in my opinion, than the newer medication on the market, namely buprenorphine.

Buprenorphine is sold as a generic and also in the branded combinations Suboxone, Zubsolv, and Bunavail, which contain both buprenorphine and naloxone. With the exception of Probuphine (a new buprenorphine sub-dermal implant), buprenorphine products are dissolved in the mouth (Suboxone and Zubsolv), or applied to the inside of the cheek (Bunavail). Buprenorphine is a partial opioid agonist that has a “ceiling effect”, making overdoses and fatal respiratory depression much less likely than methadone or abused full-agonist opioids like oxycodone, heroin, etc. Buprenorphine comes alone as a medication, and this form has a higher street value, and a greater propensity for diversion or misuse (intravenous administration). In my practice, straight buprenorphine is preferred only in our pregnant patients (naloxone is contraindicated in pregnancy). Naloxone is an opiate “blocker” which is not active or absorbed to any significant extent when administered orally, and there is also a deterrent to diversion and misuse, as the opiate blocker reduces or eliminates any “high” which could be obtained from intravenous use of the product. This is why combination buprenorphine/naloxone products are generally preferable to prescribe.

The DATA 2000 program is a special training course which familiarizes physicians with buprenorphine products and enables certain physicians to prescribe the products for out-patient management of opiate use disorder. This enables patients to live a fairly normal life- going to work, maintaining relationships, etc. Downsides of buprenorphine treatment include the fact that the patient remains dependent on an opioid and cost. Unfortunately, many insurances still play the “prior authorization” game with these medications. What this means is that, if I write a prescription of Suboxone for one of my patients and they take it to the pharmacy, many times the insurance company will ask me to fill out papers and jump through hoops before they will cover the medication. This can take 3-4 days, and in the meantime my patient is either very ill, or already relapsed because of severe withdrawal symptoms. This is very problematic, but I am optimistic that insurers will be forced to increase their coverage for MAT.

You may notice that I listed ongoing opiate dependence as a drawback applicable to both medications. It is important here to differentiate between DEPENDENCE and ADDICTION. Dependence is a physiologic phenomenon experienced by any animal given regular opioids, and is characterized by withdrawal symptoms upon sudden discontinuation. ADDICTION is distinct from dependence in that addiction is defined as compulsive, out-of-control drug use, despite negative consequences. Thus, a patient being treated with buprenorphine is quite naturally DEPENDENT, but generally devoid of harmful addict behaviors and living a normal existence- i.e. he or she is not “addicted”. This ends up being the rationale for the incorporation of MAT into the treatment paradigm of opiate use disorder- the very real concept of harm reduction. We are essentially trading a condition of dependence and addiction for one of solely dependence, and we must at times believe that this is a “win”!

We must accept that the outcome REALITY of the majority of our patients is either relapse or death- PERIOD, NOT the all-too-elusive “abstinence”. Given the REALITY that 90% of our opiate use disorder patients will relapse, and the REALITY that the substances our patients are putting in their bodies nowadays are often fatal with a SINGLE USE OF MINUTE AMOUNTS, we as addiction professionals MUST come to grips with the REALITY of considering MAT in the management of our opiate use disorder patients. In the final analysis, the REALISTIC question we must ask ourselves for the vast majority of our patients is: “is my patient better off alive and using MAT, or dead because of blind allegiance to our industry’s traditional, draconian ideals”?

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