Intended for healthcare professionals


Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review

BMJ 2002; 325 doi: (Published 02 November 2002) Cite this as: BMJ 2002;325:991
  1. Toshi A Furukawa, professor (furukawa{at},
  2. Hugh McGuire, trials search coordinatorb,
  3. Corrado Barbui, psychiatristc
  1. a Department of Psychiatry, Nagoya City University Medical School, Nagoya 467-8601, Japan
  2. b Cochrane Collaboration Depression, Anxiety, and Neurosis, Health Services Research, King's College Institute of Psychiatry, London SE5 8AF
  3. c Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Ospedale Policlinico 37134 Verona, Italy
  1. Correspondence to: T A Furukawa
  • Accepted 24 June 2002


Objective: To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.

Design: Systematic review of randomised trials comparing low dosage tricyclics (100 mg/day) with placebo or with standard dosage tricyclics in adults with depression.

Main outcome measures: Relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression. Relative risks of overall dropouts and dropouts due to side effects.

Results: 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.

Conclusions: Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of various dosages.

What is already known on this topic

What is already known on this topic Tricyclics are still prescribed as often as selective serotonin reuptake inhibitors and other newer antidepressants worldwide

Experts have often claimed that clinicians prescribe tricyclics at less than adequate dosages

What this study adds

What this study adds Tricyclics at dosages below the recommended range are more effective than placebo

They may or may not be as effective as standard dosage tricyclics but result in fewer dropouts due to side effects

The minimum effective dosage and ranges for antidepressants has not been established—a simple set of numbers that every practising doctor and patient would want to know


  • Funding St Luke's Life Science Institute, Tokyo, Japan provided 700 000 yen (£3659; $5696; 5835).

  • Competing interests TAF has received fees for speaking from several pharmaceutical companies, some of which manufacture various types of antidepressants including paroxetine, fluroxamine, milnacipran.

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