The reality of America’s opioid addiction and overdose problem has reached the lay press. As overdose deaths begin to outpace car accidents as the #1 cause of accidental deaths, the Opioid Crisis has people’s attention [1,2].
How we deal with this epidemic in the Emergency Department has been a topic of hot debate, both in publication and in the Free Open Access Medical Education (FOAM) world.
To dive into these topics, we sat down with Dr. Ken Starr, an Emergency and Addiction medicine specialist, to review buprenorphine. Buprenorphine is the opioid agonist agent in Suboxone and the sole active agent in Subutex, which has seen increasing popularity for both the treatment of withdrawal and maintenance of abstinence for the opioid addicted.
The Basics of Buprenorphine
Pharmacology: Buprenorphine has a high affinity (really wants to grab) for the mu-opioid receptor, but a weak or partial agonism (weakly activates) of the receptor. It also is an antagonist at the kappa receptor.
Why this is important: The strong affinity for the mu-opioid receptor means buprenorphine can, metaphorically, kick other opioids (heroin, for example) off the receptor. In this way it can actually precipitate withdrawal in someone actively using high potency opioids. The weak/partial agonism of the mu-receptor is where the withdrawal treatment and maintenance of abstinence come into play. By weakly triggering the mu-opioid receptor, buprenorphine can drastically improve symptoms of withdrawal. It has been shown in this way to help patients maintain their sobriety or abstinence . Because it only weakly or partially activates the receptor, buprenorphine will not cause euphoria (at least in the opioid tolerant patient).
Pharmacodynamics and kinetics: Buprenorphine is a medication with a “ceiling effect” which means there is a dose at which there is no further effect on the targeted receptor (the mu opioid receptor). With an apparent half life of 37 hours, this ceiling effect comes into play . As we discuss in this podcast, you can essentially “load” a patient with buprenorphine in the ED. To do this a provider gives multiple doses, reaching a relatively high plasma concentration and setting the patient well into the ceiling effect level. As they metabolize the medication they continue to have effect for some time while they pursue and are placed in outpatient therapy.
Does it work?
This is all good news in theory, but does buphrenorphine actually help patients? Sadly, there is a scarcity of data to really hang our hat on.
Detox effect- In a small study (N=49), buprenorphine was seen to be superior to clonidine in treating opioid withdrawal symptoms, as measured by a clinical opiate withdrawal scale (COWS) .
The best Emergency Department study is probably D’Onofrio et al out of Yale where the initiation of buprenorphine in the ED was seen to improve engagement in outpatient treatment programs and decrease self reported illicit opioid use . That said, it did not decrease HIV risk or positive urine opioid tests.
Maintenance of Abstinence: Buprenorphine has compared favorably to some higher dose methadone therapy plans for maintenance of abstinence from illicit opioids . These results, however, are not consistent across the literature .
One of the major arguments against methadone and buprenorphine therapy is that we are “trading one addiction for another.” As an initial believer in this philosophy, I can see why some would form this opinion. When we compare the physical and psychological risks and strain of illicit opioid use, the resource and monetary strain on society, etc.- the benefits of controlled therapy become more clear. It may be as simple as the distinction between addiction and dependence, but there are clear arguments it benefits both the individual and society.
How to Prescribe?
Buprenorphine comes in 8 mg sublingual tablets. In the medication Suboxone, it is coupled with 2 mg naloxone as a taper deterrent. The typical maintenance dose of suboxone (buprenorphine) is 16 mg/day.
In the emergency department, patients can be “loaded” as noted above. This typically consists of administration of one sublingual tablet (8 mg) followed by a short observation before administration of one (16 mg) or two (24 mg) tablets. This gets plasma concentration up above the ceiling effect and theoretically allows for continued efficacy while the patient is placed in outpatient therapy and finds a long term prescriber.
To write a prescription for buprenorphine, a physician must take an 8 hour course to allow for an “x waiver” to be applied to their DEA. This would allow the ED physician to write for suboxone prescriptions and avoid the need to load the patient as noted above .
Ok, that was a lot. Let’s hear some of these points discussed in our interview with our expert, Dr. Ken Starr.
D’Onofrio G, MD, MS, O’Connor P, MD, MPH, Pantalon M, PhD, Chawarski M, PhD, Busch S, PhD, Owens P, MS, Bernstein S, MD, and Fiellin D, MD. Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention. J Gen Intern Med. 2017 Jun; 32(6): 660–666. [https://link.springer.com/article/10.1007/s11606-017-3993-2]
Walsh SL1, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. [https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1994.71]
Ziaaddini H, Nasirian M, Nakhaee N. A comparison of the efficacy of buprenorphine and clonidine in detoxification of heroin-dependents and the following maintenance treatment. Addict Health. 2010 Winter-Spring; 2(1-2):18-24. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905506/]
Johnson RE, Jaffe JH, Fudala PJ. A controlled trial of buprenorphine treatment for opioid dependence. JAMA. 1992 May 27;267(20):2750-5. [https://jamanetwork.com/journals/jama/article-abstract/397410]
Ling W, Wesson DR, Charuvastra C, Klett CJ. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Arch Gen Psychiatry. 1996 May;53(5):401-7. [https://jamanetwork.com/journals/jamapsychiatry/article-abstract/497574]