Three-year outcomes of maintenance nortriptyline treatment in late-life depression: A study of two fixed plasma levels

Objective: This study compared the long-term efficacy of two fixed plasma l evels of nortriptyline in preventing or delaying recurrence of major depres sion in elderly patients and in minimizing residual depressive symptoms and somatic complaints. Method: The authors randomly assigned 41 elderly patie nts with histories of recurrent major depression to 3-year, double-blind ma intenance pharmacotherapy using nortriptyline, with controlled plasma conce ntrations of 80-120 ng/ml versus 40-60 ng/ml. The authors compared times to , and rates of, recurrence of major depression. They also compared frequenc ies of side effects, noncompliance episodes, and subsyndromal symptomatic f lare-ups. Results: Major depressive episodes recurred for six (29%) of 21 s ubjects in the 80-120-ng/ml condition and eight (40%) of 20 subjects in the 40-60-ng/ml condition, a nonsignificant difference. Most recurrences took place in the first year of maintenance treatment. Hamilton depression score s in the subsyndromal range (higher than either 10 or 7) occurred significa ntly more often at 40-60 ng/ml, while constipation occurred significantly m ore often at 80-120 ng/ml. The proportions of patients reporting missed dos es did not differ. Conclusions: Maintenance pharmacotherapy with nortriptyl ine at 80-120 ng/ml is associated with fewer residual depressive symptoms, that is, a less variable long-term response, than pharmacotherapy at 40-60 ng/ml, but constipation is more frequent and there is no difference in recu rrence of syndromal major depressive episodes. Treatment at 80-120 ng/ml ma y be preferable, because of fewer residual symptoms and less variability of response, as long as side effect burden can be managed successfully.