Metyrapone‐induced withdrawal symptoms

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.