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

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Abstract
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 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 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