Pharmacokinetics and efficacy of maprotiline and amitriptyline in endogenous depression: a double-blind controlled trial
Montgomery, S.A.; Mcauley, R.; Montgomery, D.B.; Dawling, S.; Braithwaite, R.A.
Clinical Therapeutics 3(4): 292-310
1980
ISSN/ISBN: 0149-2918 PMID: 7023677 Document Number: 164303
The efficacy of maprotiline and amitriptyline and steady-state plasma levels were compared on 41 patients. The usefulness of single oral dose pharmacokinetics or the simple 24 or 48 h spot plasma level tests were determined as predictors of clinical response. Patients were randomly assigned to treatment with maprotiline or amitriptyline. Response was determined by improvement in the Montgomery Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale and the Beck Self Rating Inventory. Thirty-six patients completed 4 wk of treatment, at which time there was no significant difference in response between the 2 groups. Patients completed 6 wk of treatment. Those treated with maprotiline had a significant improvement in the MADRS; improvement in the other 2 scales did not achieve statistical significance. Significantly more maprotiline-treated patients responded than did amitriptyline-treated patients. The incidence of side effects steadily declined in the maprotiline group; by the 3rd wk there were fewer complaints than at the start of the study. In the amitriptyline group, side effects increased until the 3rd wk and remained higher than at baseline throughout the trial. In the amitriptyline group the mean steady-state plasma level of amitriptyline plus nortriptyline exceeded the recommended upper limit of 200 .mu.g/l. A significant correlation was seen between high plasma levels of nortriptyline and amitriptyline plus nortriptyline and lack of response to treatment. Better responses were obtained in patients with moderate levels of these drugs. No significant relationship was found between plasma maprotiline levels and clinical response. Reciprocal clearance of amitriptyline and maprotiline correlated significantly with mean steady-state plasma concentrations; the half-life was less reliable as a predictor of plasma levels. Spot levels of amitriptyline, nortriptyline and amitriptyline plus nortriptyline were significantly correlated with steady-state plasma levels; the best correlation was observed for the 48 h spot level predictors of amitriptyline and amitriptyline plus nortriptyline. Maprotiline may be a more effective antidepressant than amitriptyline and appears to lack the disadvantages of the latter agent.