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 levels of nortriptyline in preventing or delaying recurrence of major depression in elderly patients and in minimizing residual depressive symptoms and somatic complaints. METHOD: The authors randomly assigned 41 elderly patients with histories of recurrent major depression to 3-year, double-blind maintenance pharmacotherapy using nortriptyline, with controlled plasma concentrations 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 frequencies of side effects, noncompliance episodes, and subsyndromal symptomatic flare-ups. RESULTS: Major depressive episodes recurred for six (29%) of 21 subjects 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 scores in the subsyndromal range (higher than either 10 or 7) occurred significantly more often at 40–60 ng/ml, while constipation occurred significantly more often at 80–120 ng/ml. The proportions of patients reporting missed doses did not differ. CONCLUSIONS: Maintenance pharmacotherapy with nortriptyline 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 recurrence of syndromal major depressive episodes. Treatment at 80–120 ng/ml may be preferable, because of fewer residual symptoms and less variability of response, as long as side effect burden can be managed successfully.