Q&A

Low-dose tricyclics effective for depression

J Fam Pract. 2003 May;52(5):349-364
By
Eugene R. Bailey, MD
Kenneth M. Johnson, III,, MD
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  • BACKGROUND: Despite widespread marketing of selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants, TCAs are prescribed as often as SSRIs (albeit not all of these prescriptions are for major depressive disorder). Yet evidence regarding the efficacy of TCAs is limited.
  • POPULATION STUDIED: The authors performed a comprehensive search of the Cochrane Collaboration’s Depression, Anxiety and Neurosis Controlled Trials Registry (a compilation of studies in MEDLINE, Embase, CINAHL, PsychINFO, PSYINDEX, and LILACS). They also searched major psychiatric and medical journals, ultimately identifying 2418 studies. After excluding trials that didn’t meet their criteria, they had 39 double-blind, randomized-controlled trials for inclusion. Six of 39 trials compared low-dose TCAs with standard doses of TCAs (551 participants), and 35 of 39 trials compared low-dose TCAs with placebo (2013 participants).
  • STUDY DESIGN AND VALIDITY: Two authors determined independently whether studies met inclusion criteria, and then graded the eligible studies for quality. The studies included were not consistent for population (primary care vs psychiatric, comorbidities, and definition of depression), medication and duration of treatment (4 to 52 weeks), and outcomes measured. Significant heterogeneity existed only for the response rates at 4 to 6 weeks in the TCA vs placebo groups. When the smallest 5 studies reporting the differences were excluded, the results were no longer heterogeneous.
  • OUTCOMES MEASURED: Outcomes included response rates at 4 weeks, 6 to 8 weeks, and 3 to 12 months.
  • RESULTS: Low-dose TCAs (75–100 mg/day) were more likely than placebo to bring about a response at 4 weeks (relative risk (RR)=1.65; 95% confidence interval [CI]=1.36–2.00, number needed to treat [NNT] [benefit]=6), 6 to 8 weeks (RR=1.47; 95% CI=1.12–1.94, NNT [benefit]=5), and 3 to 12 months (RR=2.14; 95% CI=1.41–3.26, NNT [benefit]=3).
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PRACTICE RECOMMENDATIONS

Minimum effective dosage and ranges for antidepressants have not been established. While studies suggest that lower-dose tricyclic antidepressants (TCAs) may be as effective as higherdose TCAs, dose comparison studies with other antidepressants have not been conducted.

Low-dose TCAs may not be as effective as standard doses, but they do have fewer treatment dropouts due to side effects, and thus patients may have better long-term compliance. Regular monitoring of patient rate of reduction in severity of depression should be used to help determine optimal individual dosing.

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Achieving the best outcome in treatment of depression