Clonidine Plus MAT Improves Treatment Outcomes

What is clonidine?

During the late 1970s, my colleague, Dr. Herb Kleber, and I introduced a novel neuroanatomical model to explain the pathophysiology of opioid withdrawal and put forth our contention that addiction was not simply a matter of avoiding withdrawal. Using what was then a novel new drug, clonidine, we were able to effectively detox heroin and methadone addicts in half the time, and without the surge of norepinephrine release from the locus coeruleus. This minimized the agitation and somatic anxiety that can be unbearable for some patients.

This helped prove our conviction that addictive disease was the result of numerous and largely unknown factors, and not simply to avoid withdrawal. In spite of effectively and humanely withdrawing addicts from opioids, we also discovered that something was clearly different and unique about their brain and behavior. After being clean and sober for 6-8 months in a safe and secure rehab environment, most addicts returned to using heroin as soon as the door was unlocked. This looked like Pavlovian principles on steroids. Although it was not due to avoidance of withdrawal symptoms, the answer remained unclear.

In some ways, we have traveled light years in furthering our understanding of the brain and addictive disease. Yet, relapse remains the norm and not the exception for opioid addicts. The development and use of naltrexone in the 1990s followed by buprenorphine has helped many addicts achieve a better quality of life. Yet, relapse remains the norm.

In a recent placebo-controlled clinical trial by Kowalczyk, et al, participants were given (0.3 mg/d) of clonidine or placebo during 18 weeks of Medication-Assisted Treatment (MAT) with buprenorphine, and documented their mood and activities via a pre-programmed smart phone.

Study participants receiving clonidine in addition to buprenorphine had increased abstinence from opioids and were able to decouple their stress from drug craving. Additionally, participants in the buprenorphine-plus-clonidine group, not only experienced longer periods of abstinence, but were also better in managing, or coping with their “unstructured” time. In other words, clonidine helped persons deal with their boredom and inability to create or engage in healthy activities, which is a strong predictor of relapse.

Why Does This Matter?

The study replicates previous research demonstrating that 1.) unstructured time, especially during early recovery is a trigger and predictor of relapse, 2.) engaging in responsible or helpful activities is associated with better outcomes among patients receiving Medication-Assisted Treatment, and 3.) clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have experienced.

From a personalized-medicine perspective, these data are a good reminder that addiction is a multifaceted disease requiring a multimodal approach. It is not treatable with any singular intervention. At best, psychopharmacology is adjunctive. And remember before any MAT, many addicted persons enjoyed sustained recovery via 12-step programs.