Buprenorphine Rescue from Naltrexone-Induced Opioid Withdrawal During Relatively Rapid Detoxification from High-Dose Methadone: A Novel Approach

| April 16, 2008 | 0 Comments

by Vanessa Urban, MD; and Rolly Sullivan, MD
Dr. Urban is Clinical Instructor and Dr. Sullivan is Professor, Department of Behavioral Health and Psychiatry, West Virginia University of Medicine, Morgantown, Virginia.

Abstract

This small series of case reports illustrates a significantly faster and well tolerated method for a relatively rapid detoxification from high-dose methadone as compared to traditional methadone detoxification regimens. After inducing a withdrawal state using oral naltrexone, the patients were quickly “rescued” with buprenorphine (a combination of buprenorphine/naloxone). By administering a medication that attenuates withdrawal symptoms, patients immediately began to feel better and were better able to invest themselves in the overall treatment. The patients were then able to taper off opioids in a matter of days with minimal discomfort. The average length of stay was seven days, and no patients left before completing the program.

Key Words

methadone, buprenorphine, suboxone, naltrexone, revia, rapid detoxification, high dose

Introduction

Opioid dependence is a growing concern in the United States. The 2003 National Survey on Drug Use and Health showed 3.2 percent of Americans misused prescription drugs. Abstinence remains the goal of treatment, but often patients relapse when going through the physical withdrawal symptoms that present with opioid cessation. In today’s managed healthcare climate, there is an ever-increasing pressure to treat patients quickly, and this is especially true for inpatient treatments. Often patients request a faster method of detoxification than the standard methadone taper as set forth by methadone clinics.[1 ]We propose a novel approach to address the issue of providing a relatively rapid method of inpatient detoxification from high dose methadone (>70mg in our review) by using a combination of oral naltrexone followed by sublingual buprenorphine/naltrexone.

Methods

The author performed a 12-month retrospective chart review of all inpatients of the addiction unit at a university hospital in Morgantown, West Virginia. Five patients (3 men, 2 women) each requesting detoxification from methadone were admitted on doses of methadone ranging from 70mg to 130mg per day. All endorsed receiving their regular methadone dose the day prior to admission. Patients chosen for this retrospective chart review received naltrexone followed by buprenorphine/naltrexone during their detoxification. Information was obtained from medical records.
Background. Buprenorphine acts as a Mu partial agonist and a moderate kappa antagonist.[1–3] The properties that make it ideal as a detoxification medication are its high affinity for and slow dissociation from the Mu opioid receptors, its minimal withdrawal when stopped abruptly, its minimal euphoric effects, its safety in overdose, and its ability to block receptors from illicit opioid ingestion.[1,4,5] There is preliminary data that it may also reduce opioid cravings.[1,4] Because buprenorphine has a higher affinity for the opioid receptor than methadone, but only 40 percent of methadone’s efficacy, a direct methadone to buprenorphine/naloxone regimen has proven clinically difficult unless the daily methadone dose is 30mg or less.[1,6]

Participants. After a chart review spanning a 12-month period, five patients met the inclusion criteria of a maintenance methadone dosage of 70mg or more per day. Patients included in this case review were adults 18 years of age or older who had a full history and physical as well as standard laboratory work done at the time of their admission. The daily methadone doses of the five cases in this review were 70mg, 75mg, 100mg, 100mg, and 130mg.

Procedure. On admission, all patients were given the choice of clonidine 0.2mg tablets on an as needed basis or weekly TTS-2 (0.2mg/24 hours) clonidine patches. The patients were then educated regarding the induction of opioid withdrawal with naltrexone as well as the pharmacologic properties of sublingual buprenorphine/naloxone that render it ineffective if not taken sublingually. It was explained that after the initial oral dose of naltrexone 25mg, opioid withdrawal symptoms typically took 30 to 45 minutes to be strong enough to warrant a buprenorphine/naloxone dose. After this orientation to the procedure, the patients were then given their initial naltrexone doses, encouraged to self-report any symptoms of opioids withdrawal, and were monitored by the staff for signs and symptoms of withdrawal.

Assessments. Full opioid withdrawal was assessed by staff’s observation of vital signs, onset of nausea, vomiting, diarrhea, rhinorrhea, and yawning in conjunction with patient’s self-reporting of muscle aches, abdominal cramping, irritability, and anxiety. An initial dose of 4 to 6mg of sublingual buprenorphine/naloxone was then given. The dosage for maintenance of symptom relief was then obtained during the first 24-hour period of buprenorphine/naloxone treatment. This dose was then tapered off over several days based on the individual’s clinical course.

Results

The induction/rescue technique had promising results. Typical opioid withdrawal symptoms occurred within 45 minutes of the naltrexone dose, and using it to induce withdrawal circumvented a premature methadone to buprenorphine/naloxone transfer. All patients placed on the intermediate step of naltrexone induction followed by buprenorphine/naloxone rescue completed the detoxification process and expressed gratitude at the efficiency of the process.

Discussion

Traditionally, detoxification from high-dose methadone is a long process. The lowest daily dose of methadone we treated was 70mg daily, which would have taken 15 weeks using a traditional outpatient taper. Our average detoxification was seven days with naltrexone-induced withdrawal followed by a sublingual buprenorphine/naloxone rescue.

We opted to use the “rescue” approach rather than a direct methadone to buprenorphine approach for several reasons. The first was that withdrawal could be quickly and predictably initiated, thus starting buprenorphine treatment sooner. Another was the concern that if a direct methadone to buprenorphine transfer is initiated, significant withdrawal would result due to buprenorphine being a partial agonist but at the same time having the highest affinity for the Mu receptors. Therefore, the withdrawal would not be able to be reversed by the addition of other opioids, which could potentially cause a higher treatment dropout rate. The final reason was that it was felt in a dependent population, a medicine that could quickly reverse withdrawal symptoms would increase patient confidence in the medication and thus increase overall adherence with treatment. Although patients had to enter naltrexone-induced withdrawal before receiving buprenorphine/naloxone, they then had a sufficient “rescue” experience, which allowed them to complete the program. The total number of patients reviewed was small, but there were no dropouts with this method. At the time of the review, the issue of natural versus induced withdrawal was not addressed in the literature. It would be helpful if double-blind, placebo-controlled studies were done to compare outcomes between the methods of predicating withdrawal versus waiting for the natural course of withdrawal to ensue before initiating buprenorphine treatment.

Conclusion

Although this is a small series of cases, it raises some interesting possibilities. Methadone maintenance dosages usually range from 80mg to 120mg, and current literature endorses a slow 3 to 5mg per week taper of this drug.6 Patients’ attempts to wean themselves faster than this may foster relapse as signs and symptoms of withdrawal emerge, thus discouraging them from future attempts. Buprenorphine offers relief from withdrawal and acts as a deterrent to future illicit opioid usage secondary to its high opioid receptor affinity. It may prove beneficial to study the methods outlined in this paper of a naltrexone-induced withdrawal followed by a buprenorphine/naloxone rescue in controlled clinical trials.

References

1. Graham W, Schultz TK, Mayo-Smith MF, et al (eds). Principles of Addiction Medicine, Third Edition. Maryland, Md: American Society of Addiction Medicine, Inc., 2003.
2. Rothman RB, Ni Q, Xu H. Buprenorphine: A review of the binding literature. In: Cowan A, Lewi JW (eds). Buprenorphine: Combating Drug Abuse with a Unique Opioid. New York, NY: Wiley-Liss, 1995:19–30.
3. Johnson RE, Strain EC, Amass L. Buprenorphine: How to use it right. Drug Alcohol Depend 2003;70:S59–S77.
4. Fudala, PJ, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003;349(10):949–58.
5. Johnson, RE. Buprenorphine and naloxone for heroin dependence. Curr Psychiatry Rep 2000;2(6):519–26.
6. McNicholas L. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction: A Treatment Improvement Protocol TIP 40. Department of Health and Human Services, 2004. Available at: http://www.samhsa.gov/SAMHSA_News/VolumeXII_4/article7.htm. Access date: April 7, 2008.

Category: Case Study, Psychiatry, Substance Use Disorders

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