Prescription medicine primer: maintenance treatment of opiate addiction.
Subject: Detoxification (Substance abuse treatment) (Methods)
Detoxification (Substance abuse treatment) (Analysis)
Drugs (Prescribing)
Drugs (Health aspects)
Authors: Schmetzer, Alan D.
Bhagar, Harpriya "Sonya" A.
Pub Date: 06/22/2008
Publication: Name: Annals of the American Psychotherapy Association Publisher: American Psychotherapy Association Audience: Academic; Professional Format: Magazine/Journal Subject: Psychology and mental health Copyright: COPYRIGHT 2008 American Psychotherapy Association ISSN: 1535-4075
Issue: Date: Summer, 2008 Source Volume: 11 Source Issue: 2
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 180860864
Full Text: [ILLUSTRATION OMITTED]

Of all the modern treatments for addiction, perhaps the most controversial is the use of maintenance opioid substitution in the treatment of intravenous drug addiction. "Maintenance" is defined as the continuation of prescribing some compound similar enough to stave off withdrawal to a person who is already addicted. With current concerns about the human immunodeficiency virus infection and other serious health complications, harm reduction is the primary argument for maintenance treatment of addiction to intravenous abuse of drugs such as heroin and opioid pain medications. In this country, we have used such medications as methadone, long-acting methadone, and, more recently, buprenorphine for maintenance, although in other countries the addicted person's drug of choice, such as heroin, might be used along with some sort of "clean" needle giveaway program.

Methadone (Dolophine[R]) is a synthetic opioid usually started orally at 30 mg or less per day and increased to the lowest dose that effectively blocks or stops use of other opioids (known as "chipping") for a given patient, usually 50 mg per day or more. Although it can be given in a tapering dose as a withdrawal agent, it is frequently used as a maintenance strategy, administered daily dissolved in juice or water. It has most likely been studied more than any of the others listed. Because it is given once a day by mouth, causes less sedation, and can be obtained legally at a reasonable cost, people taking methadone will not develop new IV-related complications, can be successful in the free-market workplace, and are less likely to resort to criminal activities. These have been the major arguments for its use. Opponents point out that methadone maintenance simply substitutes one addiction for another, that withdrawal from methadone takes longer (and some patients report it being more severe) than from heroin, and that it does have its own side effects. The latter include some sedation, especially early in treatment; dizziness; nausea; vomiting; headaches; and excessive sweating. If the dose is too high, respiratory depression and cardiovascular collapse may occur, which can be fatal. Very little (only a fraction of one percent) methadone is diverted to "street use," but this remains a serious law-enforcement concern, and thus methadone is highly regulated by federal agencies such as the Drug Enforcement Administration (DEA) and the Food and Drug Administration (FDA).

Levo-alpha-acetylmethadol or LAAM (Orlaam[R]) is a longer-acting derivative of methadone that became available in the United States in 1993. Given less frequently than regular methadone, patients were seen in clinic only three times a week for LAAM as opposed to daily visits for traditional methadone. However LAAM was removed from the European market in March 2001 following reports of severe cardiac-related adverse events, including QT-interval prolongation, Torsades de Pointes, and cardiac arrest. In September 2003, Roxane Laboratories, Inc. discontinued the sale and distribution of Orlaam[R] in the United States as well.

More recently, the FDA approved buprenorphine (Subutex[R]) for use in opioid withdrawal and maintenance. Unlike methadone and LAAM, it is only a partial agonist at the opioid receptor. Therefore, it can substitute for opiates in addicted people but may also precipitate withdrawal symptoms if used with someone who is still actively abusing an opioid. Adverse effects include sedation and constipation. Buprenorphine may be given in a physician's private office with appropriate physician training (available at http://www.aaap.org/buprenorphine/ buprenorphineonline.htm or at various training sites around the country) rather than in a specially licensed opioid treatment program. The usual starting dose is between 0.8 mg and 4 mg, with a maximum recommended daily dose of 32 rag. When coupled with naloxone, an opioid antagonist, in a sublingual tablet called Suboxone[R] the risk of abuse is further diminished. When it is taken only as directed--placing the tablet under the tongue and allowing it to dissolve--the naloxone component is poorly absorbed, but if the tablet is crushed and put into solution for injection, the naloxone is activated, thus blocking the buprenorphine (or any other opioid, for that matter) from attaching to the brain's [mu]-opioid receptors, thereby reducing or eliminating any intoxicating effect.

It must be mentioned that there are non-substitution treatments available for opioid addiction, although their use has generally been limited due to poor patient compliance. Naltrexone (ReVia[R]) is an opiate antagonist related to naloxone, and a daily 50 mg dose will block the effects of opioids, thus decreasing reinforcement for continued use. Some patients also report decreased cravings when taking this medication. Adverse effects include nausea, headache, fatigue, restlessness, and sleep disturbance, as well as occasional dysphoria or outright depression. Naltrexone is often given at mealtime to mitigate the gastrointestinal (GI) side effects. Vivitrol[R] is naltrexone in an extended-release intramuscular suspension intended for monthly use. Although approved by the FDA only for the treatment of alcohol dependence, it is an obvious way around the adherence issue with daily tablets of naltrexone in opioid dependence as well. Nalmefene (Revex[R]) is a long-acting form of naltrexone, also given at a daily oral dose of 50 mg. Its use in the United States has not been particularly robust, because effectiveness still relies on oral intake. Both of these longer-acting variants have essentially the same side effect profile as naltrexone, although GI upset may be less likely with the injectable formulation. None of the medications discussed above are recommended as stand-alone treatments--all must be coupled with some form of group and/or individual counseling or psychotherapy in order to be significantly effective.

Earn CE Credit

Take CE tests for free online at www.americanpsychotherapy.com or see the questions for this article on page 27.

1. The best-studied maintenance medication for treating apioid dependence is:

a) buprenorphine

b) LAAM

c) methadone

d) naloxone

2. Besides use in maintenance for opioid dependence, methadone may also be used for:

a) alcohol dependence

b) barbituate withdrawal

c) marijuana abuse

d) opioid withdrawal

3. LAAM stands for:

a) LAminating AntiMicrobial

b) Levo-Alpha-AcelylMethadol

c) Long-Acting A-Methadone

d) Long-Acting Addiction Maintenance

4. Removal of LAAM from the marketplace was due to problems with:

a) the heart

b) the kidneys

c) the liver

d) the pancreas

5. Naltrexone may be given at mealtime to reduce side effects within the:

a) cardiac system

b) central nervous system

c) pulmonary system

d) gastrointestinal system

6. Suboxone is administered:

a) intramuscularly

b) intrathecally

c) intravenously

d) sublingually

Benefits of Methadone Maintenance Treatment (MMT)

MMT costs about $13 per day and is considered a cost-effective alternative to incarceration (Office of National Drug Control Policy, 1998).

MMT has a benefit-cost ratio of 4:1, meaning $4 in economic benefit accrues for every $1 spent on MMT (COMPA, 1997).

Research suggests that MMT significantly decreases the rate of HIV infection for those patients participating in MMT programs (Firshein, 1998).

MMT allows patients to be free of heroin addiction. The National Institute on Drug Abuse found that, among outpatients receiving MMT, weekly heroin use decreased by 69%.

Patients were no longer required to live a life of crime to support their habit, and criminal activity decreased by 52% among these patients. Full-time employment increased by 24%. In a 1994 study of drug treatment in California, researchers found that rates of illegal drug use, criminal activity, and hospitalization were lower for MMT patients than for addicts in any other type of drug treatment program.

Information retrieved May 8, 2008, from http://www.whitehousedrugpolicy.gov/publications/factsht/ methadone/index.html

References

Lowinson, J.H., Ruiz, P., Millman, R.B., & Langrod, J.G. (eds.). (2005). Substance abuse: A comprehensive textbook, 4th ed., pp. 616-653. Williams & Wilkins.

Physicians' Desk Reference, 33rd edition. (2008). Thompson.

Alan Schmetzer, MD, FAPA, Master Therapist, is vice-chair of the Executive Advisory Board for the American Psychotherapy Association and has been a member of the association since 1998. He is a professor of psychiatry at Indiana University School of Medicine and can be reached at aschmetz@iupui.edu.

Harpriya A. (Sonya) Bhagar, MBBS, is an assistant professor of clinical psychiatry at Indiana University School of Medicine and is a member of the American Psychotherapy Association. She can be reached at hbhagar@iupui.edu.
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