title: Metyrapone-induced withdrawal symptoms.
abstract: The metyrapone test is widely used in endocrinological testing to assess the integrity of hypothalamic-pituitary-adrenal axis function; we have used it to study the metabolic basis of addictive disease and opioid dependence. In recent studies, we have observed that metyrapone administration in long-term methadone-maintained patients and in patients undergoing slow dose reduction to drug-free status following chronic treatment may induce a narcotic withdrawal-like syndrome. Although metyrapone is known to produce mild adverse reactions in non-opiate dependent subjects, narcotic withdrawal-like symptoms have not been previously observed or reported. The metyrapone test was administered to 15 former heroin addicts: 10 (8 male, 2 female) in steady-state methadone maintenance therapy (30 to 90 mg/d) and 5 (3 male, 2 female) in the final phase of a slow methadone dose reduction procedure (0 to 10 mg/d). Eight out of 15 methadone maintenance subjects exhibited a narcotic withdrawal-like syndrome ranging from 'moderate' to 'severe' and four additional subjects had 'mild' symptoms, occurring within 1 h after metyrapone administration, and resolving within 2 h of onset. No significant symptoms were seen in 3 methadone maintained subjects nor in any of 9 normal volunteers (7 male, 2 female). The mechanism by which metyrapone induces symptoms resembling narcotic withdrawal in opiate-dependent individuals is unknown but physicians performing this test should be aware of this possible response.
authors.affiliation: Rockfeller University, New York, New York 10021.
authors.forename: J A
authors.initials: JA
authors.lastname: Kennedy
authors.forename: N
authors.initials: N
authors.lastname: Hartman
authors.forename: R
authors.initials: R
authors.lastname: Sbriglio
authors.forename: E
authors.initials: E
authors.lastname: Khuri
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000328:Adult; D005260:Female; D006556:Heroin Dependence / Q000534:rehabilitation*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008797:Metyrapone; D010913:Pituitary-Adrenal System / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
chemical_list: D008691:Methadone; D006854:Hydrocortisone; D008797:Metyrapone