Question 12: Is the long-term use of methadone medically safe, and is it well tolerated by patients?

Answer: Yes. Studies of the long-term administration of methadone confirm that it is a medically safe drug. Long-term methadone maintenance treatment at doses of 80 to 120 mg per day is not toxic or dangerous to any organ system after continuous treatment for 10 to 14 years in adults and 5 to 7 years in adolescents.

Research Highlights

• Methadone has few adverse biological effects. There appear to be no dangerous or troubling psychological effects from long-term administration (Verdejo, Toribio, Orozco, et al., 2005).
• Methadone sometimes causes minor side effects, such as sweating, constipation, temporary skin rashes, weight gain, water retention, and changes in sleep and appetite (Lowinson et al., 1992).
• Methadone prescribed in high doses for a long period of time has no toxic effects and only minimal side effects for adult patients maintained in treatment for up to 14 years and for adolescent patients treated for up to 5 years (Kreek, 1978).
• Although early studies demonstrated no persisting abnormalities directly attributable to methadone in the functioning of five organ systems (pulmonary, cardiovascular, renal, ophthalmologic, and liver) (Krantz, Lewkowiez, Hays, et al., 2002).
• Patients maintained on methadone have no impairment in driving and have no more frequent motor vehicle accidents than people not receiving methadone maintenance treatment (Schindler, Ortner, Peternell, et al., 2004).
• The most common and enduring complaints after 6 months to 3 years of continuous methadone treatment are sweating, constipation, abnormalities in libido and sexual functioning, sleep abnormalities (insomnia and nightmares), and altered appetite (mild anorexia, weight gain) (Kreek, 1979). A study of 92 methadone-maintained patients found that the rate of global sexual dysfunction in methadone-treated men was similar to the general population but that orgasm dysfunction may respond to methadone dose reduction.
• Although euphoria and drowsiness, with occasional nausea and vomiting, can occur before tolerance develops, these side effects are most noticeable when doses are increased too rapidly. Conversely, if a heroin habit has been particularly heavy, initial methadone doses may be too low to prevent the onset of early withdrawal symptoms (Kreek, 1979).
• Life-threatening interactions of methadone with other drugs have not been identified. Drugs found to affect the metabolism of methadone include phenytoin (Dilantin) and rifampin. Opioid antagonists such as pentazocine (Talwin) and buprenorphine can cause withdrawal symptoms in methadone patients and should not be prescribed (Kreek, 1978).

Figure 26 illustrates that methadone maintenance patients, in the early stages of treatment, can experience several minor side effects: sweating, constipation, orgasm abnormalities, alterations of sexual interest, alterations of sleep and appetite, nausea, drowsiness, nervousness, headaches, body aches and pains, and chills. However, the figure also shows that many of these side effects almost disappear with long-term, high-dose methadone maintenance treatment (Hartel, 1989/1990).

References

Hartel D. Cocaine use, inadequate methadone does increase risk of AIDS for IV drug users in treatment. NIDA Notes 1989/1990;5(1).

Jaffe JHl, Martin WR. Opioid analgesics and antagonists. In: Goodman & Gilman's the Pharmacological Basis of Therapeutics. New York: Pergamon Press, 1985.

Kleber HD, Mezritz M, Slobetz F. Medical Evaluation of Long-Term Methadone-Maintained Clients. Rockville, MD: National Institute on Drug Abuse, 1980.

Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Annals of Internal Medicine 2002;137(6):501-04.

Kreek MJ. Medical complications in methadone patients. Annals of the New York Academy of Science1978;311(29):110-34.

Kreek MJ. Methadone in treatment: physiological and pharmacological issues. In: DuPont RL, Goldstein A, O’Donnell J, Brown B (eds.). Handbook on Drug Abuse. Rockville, MD: National Institute on Drug Abuse, 1979.

Lenne MG, Dietze P, Rumbold GR, Redman JR, Triggs TJ. The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving. Drug & Alcohol Dependence2003;72(3):271-78.

Lowinson JH, Marion IJ, Joseph H, Dole VP. Methadone maintenance. In: Lowinson JH, Ruiz P, Millman RB (eds.).Substance Abuse: A Comprehensive Textbook. Second Edition. Baltimore, MD: Williams & Wilkins, 1992.

Maddux JF, Williams TR, Ziegler JA. Driving records before and during methadone maintenance. American Journal of Drug and Alcohol Abuse 1977;4(1):91-100.

Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. American Journal of Cardiology 2005;95(7):915-18.

Schindler SD, Ortner R, Peternell A, Eder H, Opgenoorth E, Fischer G. Maintenance therapy with synthetic opioids and driving aptitude. European Addiction Research 2004;10(2):80-87.

Verdejo A, Toribio I, Orozco C, Puente KL, Perez-Garcia M. Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers. Drug & Alcohol Dependence 2005;78(3):283-88.

Wang D, Teichtahl H, Drummer O, Goodman C, Cherry G, Cunnington D, et al. Central sleep apnea in stable methadone maintenance treatment patients. Chest 2005;128(3):1348-56.