The daily urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG)was studied longitudinally in five unipolar depressed patients. The patients were followed first during a pretreatment period, and then during a treatment period in which amitriptyline was administered. The data we have obtained suggest that: (1) there is a wide individual variability in MHPG pretreatment levels; (2) amitriptyline modifies MHPG levels in a way which seems to be related to the pretreatment MHPG; (3) amitriptyline may produce a sustained improvement in depressive symptoms, independent of the pretreatment MHPG values, and (4) the time course of modifications in MHPG excretion is shorter than the time course of improvement in depression. Some theoretical implications of these findings are discussed in terms of the catecholamine hypothesis of affective disorders.

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