Methadone Maintenance Treatment and St. John’s Wort

Abstract

St. John’s wort, a popular over-the-counter drug for treatment of depression, might reduce concentrations of drugs such as cyclosporin and indinavir and lead to drug resistance and treatment failure. No studies as yet have examined its influence on methadone plasma levels. The trough methadone plasma levels were measured in four patients (2 males, median age: 31 years; range 19 - 40 years) in methadone maintenance treatment just before the introduction of St. John’s wort (900 mg/d) and after a median period of 31-day treatment (range 14 - 47). The study was proposed to addict patients about to start an antidepressant therapy. Introduction of St. John’s wort resulted in a strong reduction of (R,S)-methadone concentration-to-dose ratios in the four median patients included, with a median decrease to 47 % of the original concentration (range: 19 % - 60 % of the original concentration). Two patients reported symptoms that suggested a withdrawal syndrome. Thus, prescription of St. John’s wort might decrease methadone blood levels and induce withdrawal symptoms which, if not correctly identified and handled (by changing the antidepressant or by increasing the methadone dose), might cause unnecessary discomfort to the patient, lead to resumption of illicit drug uses, or be a risk factor for discontinuation of the methadone or antidepressant treatment.

References

• 1 Baumann P, Meyer J W, Amey M, Baettig D, Bryoids C, Jonzier-Perey M. et al . Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.  Ther Drug Monit. 1992;  14 1-8
• 2 Bertschy G, Baumann P, Eap C B, Baettig D. Probable metabolic interaction between methadone and fluvoxamine in addict patients.  Ther Drug Monit. 1994;  16 42-45
• 3 Di Carlo G, Borelli F, Ernst E, Izzo A A. St. John’s wort: Prozac from the plant kingdom.  TIPS. 2001;  22 292-297
• 4 Drewe J, Gutmann H, Török M, Escchenmoser M, Käufeler R, Schaffner W. et al .Mechanismen der Interaktionen mit Johanniskrautextrakten. In: Rietbrock N, editor Phytopharmaka VI. Steinkopff Verlag Darmstadt; 2000: 75-81
• 5 Dürr D, Stieger B, Kullak-Ublick G A, Rentsch K M, Steinert H C, Meier P J. et al . St. John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.  Clin Pharmacol Ther. 2000;  68 598-604
• 6 Eap C B, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: Implications for the treatment of opioid dependence. Clin Pharmacokinet (in press)
• 7 Eap C B, Finkbeiner T, Gastpar M, Scherbaum N, Powell K, Baumann P. Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics.  Eur J Clin Pharmacol. 1996;  50 385-389
• 8 Kasper S. Hypericum perforatum - A review of clinical studies.  Pharmacopsychiatry. 2001;  34 (Suppl. 1) S51-55
• 9 Kosten T R, Rounsaville B J, Kleber H D. A 2.5-year follow-up of depression, life crises, and treatment effects on abstinence among opioid addicts.  Arch Gen Psychiatry. 1986;  43 733-738
• 10 Moore L B, Goodwin B, Jones S A, Wisely G B, Serabjit-Singh C J, Willson T M. et al . St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor.  Proceedings of the National Academy of Sciences of the United States of America. 2000;  97 7500-7502
• 11 Perloff M D, von Moltke L L, Stormer E, Shader R I, Greenblatt D J. Saint John’s wort: An in vitro analysis of P-glycoprotein induction due to extended exposure.  British Journal of Pharmacology. 2001;  134 1601-1608
• 12 Spina E, Pisani F, Perucca E. Clinically significant pharmacokinetic drug interactions with carbamazepine - an update.  Clin Pharmacokinet. 1996;  31 198-214
• 13 Wurglics M, Westerhof K, Kaunzinger A, Wilke A, Baumeister A, Dressman J. et al . Batch-to-batch reproducibility of St. John’s wort preparations.  Pharmacopsychiatry. 2001;  34 (Suppl. 1) S152-156