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May 26, 1999

Dose of Tricyclic Antidepressants in Elderly Patients—Reply

Author Affiliations
 

Margaret A.WinkerMD, Deputy EditorIndividualAuthorPhil B.FontanarosaMD, Interim CoeditorIndividualAuthor

JAMA. 1999;281(20):1891-1892. doi:10-1001/pubs.JAMA-ISSN-0098-7484-281-20-jbk0526

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

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