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Drug treatment of childhood depression


Depression in children and adolescents is associated with social dysfunction, academic under achievement, and suicidal behaviour. It is generally under-recognised. Prevalence is estimated at 2% in primary school children, rising to 5% in adolescents.

Traditionally, treatment has been psychological or psychoanalytical, family therapy being most popular in the UK. However, these are expensive treatments, some of unproven effectiveness.

Attention has therefore turned to antidepressant drugs, which are established in trials as effective in adult major depression. However, it is unsafe to extrapolate this evidence to young people, since these trials excluded children, in whom the condition certainly has a different epidemiology and may have a different aetiology.

Randomised controlled trials are needed to decide whether antidepressants work in childhood depression, since placebo responses are common and the condition frequently gets better naturally, making other types of evidence impossible to interpret. A number of small RCTs of tricyclic antidepressants of variable methodological quality has been conducted, generally reporting non-significant trends in favour of treatment. Hazell et al [1] recently conducted a systematic review and meta-analysis of these trials.

Systematic review of RCTs

A comprehensive search strategy was used to identify trials from electronic databases, and from manual searches of English and non-English abstracts, bibliographies, and conference proceedings.

Twelve trials were identified, all but one reporting small, non-significant treatment benefits. Nine of the twelve studies identified could be used in the meta-analysis; exclusion criteria are described, but it is unclear why the authors excluded trials where data for children and adolescents could not be separated, since they do not present separate results for the two groups.


There was one duplicate publication. Five trials presented their results as numbers improved (30/78 improved on treatment, 36/97 on placebo: pooled odds ratio 1.08 {95% CI 0.53 - 2.17}).

Six reported effect sizes, i.e. changes in the mean scores of the groups. Such continuous outcomes are more difficult to combine statistically than the above dichotomous outcomes , especially if standard deviations are not given - the authors had to assign this to some studies. Again, a trend towards improvement on tricyclics was seen, (pooled effect size = 0.35 {-0.16 - 0.86}), a positive value representing improvement: since the 95% confidence interval includes 0 no improvement), the result is not statistically significant.

The quality of the trials was investigated using published guidelines: the more rigorously conducted studies showed smaller treatment effects.

There are probably some unknown "negative" studies due to publication bias, which thus serves to strengthen the authors' conclusions.


  • this high quality systematic review identified twelve trials of tricyclics, all but one weakly positive, and concludes that tricyclics are no more effective than placebo.
  • the conclusions are supported by the likely effects of publication bias, and the less rigorous conduct of the more positive studies. over 50% responded to placebo
  • a traditional narrative review might well have concluded tricyclics were effective, on a "small samples, no smoke without fire" principle.
  • further drug research should concentrate on other agents, such as SSRIs
  • this is a good starting point for any reader interested in meta-analysis.

Practice points

  • there is no evidence that tricyclics are more effective than placebo for depression in children and adolescents
  • any possible benefits are probably outweighed by the risks of toxicity
  • these patients may well respond to non-drug strategies


1 P Hazell, D O'Connell, D Heathcote, J Robertson, D Henry . Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis. British Medical Journal 1995 310: 897-901.
Rachel Churchill
Epidemiology Research Fellow
Institute of Psychiatry
David Gill
MRC / NHS R&D Health Services Research Fellow
Institute of Health Sciences

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