Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards.

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was measured in 49 unipolar depressed outpatients to examine the relationship between pretreatment MHPG levels and therapeutic response to desipramine and amitriptyline and to determine the effects of these agents on MHPG excretion. Pretreatment MHPG excretion was greater in amitriptyline responders than amitriptyline nonresponders, but no different in desipramine responders compared to desipramine nonresponders. Pretreatment MHPG excretion did not differentiate desipramine from amitriptyline responders. Treatment for 3 weeks was associated with a decrement in MHPG excretion, particularly in the desipramine responders and combined desipramine and amitriptyline responders. Among patients within the postulated optimal desipramine plasma level range and patients with plasma amitriptyline plus nortriptyline levels greater than 70 ng/ml, high pretreatment MHPG excretion predicted therapeutic response and response was accompanied by a reduction in MHPG excretion. The interpretation of these findings is possibly confounded by the demonstration of a poor correlation (r = 0.61) between duplicate MHPG samples analyzed by a widely employed gas chromatography method and a gas chromatography/mass spectrometry technique. The methodological pitfalls encountered in the course of this investigation and their possible implications for similar studies are discussed.