Clinical Review

Methadone Maintenance Therapy for Opioid Addiction

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For many patients who acknowledge an opioid addiction, methadone can be an effective choice for eliminating the symptoms of withdrawal. Managing patients in primary care who undergo methadone maintenance treatment can be challenging, but understanding how this therapy is administered and overcoming common misconceptions can benefit both patient and provider.



Treating patients in pain has challenged health care providers for centuries. Long-term use of pain medication, particularly opioids, creates a potential for physical addiction. Addiction to opiates can cause irreparable damage in every aspect of life, including personal health, family, and finances.

For certain patients, undergoing pain management in their 20s or 30s for an acute injury, condition, or procedure can begin a cyclical pattern of abuse, physical addiction, cessation of use, and relapse. During this cycle, lack of access to legitimately prescribed opioids may lead to illegal activities, accidental overdose, or drug-related accidents that affect both the user and others.

More than 20% of Americans older than 12 report nonmedical use of various prescribed medications at some point during their lifetime.1 A large proportion of abuse involves opioid-based narcotics.

Benefits of Methadone
Methadone, a synthetic opiate whose analgesic properties were first discovered in the 1940s, was initially used to manage chronic pain. In the early 1960s, it was discovered that when taken daily at an appropriate maintenance dose, methadone benefited patients experiencing withdrawal from other opioids, including morphine and heroin.2,3 Research findings published by the NIH associate methadone maintenance treatment (MMT) with reductions in opioid drug use, crime, transmission of viral diseases, including HIV and hepatitis, and incidence of opioid-related death and overdose.4 This therapy is also credited for improved social productivity.5

Patients enrolled in MMT programs receive methadone for treatment of physical withdrawal symptoms (nausea, diarrhea, muscle aches, sweating, irritability, insomnia, "crawly" skin, anxiety) and cravings. Yet treatment with methadone is only one part of the recovery process.3 MMT also includes counseling, lifestyle modification, and other supportive services. It is important for patients to understand that constant personal reflection, ongoing counseling, and an awareness of the ramifications of continued use of other drugs all play a role in the success or failure of recovery from addiction. Methadone is not indicated for the treatment of addiction to drugs in other classes or to other substances.

Strict criteria are in place for persons to be admitted to MMT. These may include a history of at least six months' daily opioid use, positive urine screening for opioids, and the presence of active withdrawal symptoms. During the first 30 to 60 days, when daily attendance is required, the proper methadone maintenance dose is determined. Participants are monitored regularly with urine drug screening.

An integral part of MMT is to help patients reestablish a "normal" life: stability in employment, family status, finances, and personal goals. Treatment duration is highly individualized, with some patients requiring lifelong therapy to ensure continued success in recovery.3,5

How Methadone Works
Like the opioids, methadone acts on receptors in the brain that control pain and mood. Since methadone is metabolized in the liver through cytochrome P (CYP) enzymes (including CYP450, CYP3A4, CYP2C8, and CYP2D66), some care is warranted regarding use of other medications that may inhibit or induce substances in this enzyme class.7 (See table.7-10) Patients who take other medications that are influenced by CYP enzymes should be monitored for cross-reactions and may require medication adjustment. A thorough history of medication use and close monitoring of potential medication combinations are warranted.

Methadone possesses certain unique properties. Compared with most prescribed opioids (ie, hydrocodone, morphine, oxycodone), which have a half-life averaging less than three hours, the half-life for methadone exceeds 24 hours.9 This, coupled with a relatively slow onset of action, allows for once-daily dosing, making methadone a particularly effective tool in opioid addiction treatment. When taken properly, methadone is safe for the body and does not impede normal functioning. Additionally, methadone is cross-tolerant with other opioid medications,4 decreasing the likelihood of drug-seeking behavior.

Dosing is deemed adequate when the patient experiences relief from withdrawal and cravings without feeling "high" or oversedated. Because methadone is a full agonist, however, excessive dosing may produce euphoric effects.9

While methadone can in itself be physically addicting, research clearly shows that this agent helps normalize the function of body systems (particularly the immune, endocrine, and neurologic systems) that were previously impaired by opioid abuse.1

The most commonly reported adverse effects of methadone use are similar to those associated with the opioids: constipation, decreased libido, alterations in sexual functioning, amenorrhea, weight gain, and sweating. Methadone is not contraindicated for patients undergoing medical or dental procedures, but any dosing reduction should be coordinated through the MMT team. Abrupt reduction or cessation of methadone dosing may lead to drug craving and a reappearance of withdrawal symptoms.

Considerations Before MMT
For the patient who acknowledges an opioid addiction problem, the primary care provider's first step should be to attempt to wean the patient off the prescribed medication. Abruptly cutting the patient off will only generate panic and increase the likelihood of illegal behavior. If the patient is unable or unwilling to tolerate a weaning process, referral to a MMT center is indicated. To allow a reasonable time frame for the patient to enroll, providers are advised to prescribe a limited supply of the medication in question.

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