In Reply: In our study of
nortriptyline and interpersonal psychotherapy as maintenance treatments
in elderly patients with recurrent depression, we targeted and achieved
steady-state plasma levels of 80 to 120 ng/mL. Daily doses of
nortriptyline averaged 80 to 85 mg but ranged from 20 to 200 mg/d to
achieve this plasma level. Most patients tolerated this plasma level
well. Generally, about 4 to 5 weeks were needed to achieve steady-state
levels.
Dr Tan's experience has led him to support the clinical adage that
clinicians should "start low and go slow" when using tricyclic
antidepressants in older patients to minimize adverse effect burden and
to maximize safety in the initial acute-phase treatment of the
depressed elderly patient. Our data primarily addressed long-term or
maintenance therapy (over 3 years) with nortriptyline, not acute
therapy. In a second randomized, double-blind study comparing the
maintenance efficacy of 2 fixed plasma levels of nortriptyline (80-120
ng/mL vs 40-60 ng/mL), we observed comparable rates of recurrence of
major depression over 3 years (29% vs 41%, respectively), but higher
rates of subsyndromal or minor depressive episodes in patients randomly
assigned to the 40- to 60-ng/mL condition. We concluded that use of the
higher fixed plasma level was preferable for long-term control of
symptoms, provided adverse effects were acceptable or could be managed
adequately with supportive countermeasures.1