Tricyclic drugs for depression in children and adolescents

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Abstract
There is a need to identify effective and safe treatments for depression in children and adolescents. While tricyclic drugs have proven effectiveness in the treatment of depression in adults, individual studies involving children and adolescent have been equivocal. To examine whether orally administered tricyclic antidepressants are superior to placebo in the treatment of child and adolescent depression We searched the literature using CD ROM Silver Platter and On-Line MEDLINE (1966-1997) and Excerpta Medica (June 1974-1997) data bases. Terms used for the search were: the exploded terms child and depression; the Medical Subject Headings of antidepressant drugs, tricyclic and affective disorders; individual tricyclic drugs by name; names of well-known researchers in the field; and school phobia. We searched the trials database of the Cochrane Collaboration Depression, Anxiety and Neurosis Group. Abstracts in English (of English and non-English papers) were reviewed. Bibliographies of previously published reviews and papers describing original research were cross-checked. Current Contents was screened for recent publications. We contacted authors of abstracts describing "work in progress" identified in conference proceedings of the American Academy of Child and Adolescent Psychiatry to determine whether they held data which could be included in the meta-analysis. We have hand searched the Journal of the American Academy of Child and Adolescent Psychiatry to identify randomized controlled trials. Randomized controlled trials comparing the efficacy of orally administered tricyclic medication with placebo in depressed subjects aged 6-18 years. Most studies reported multiple outcome measures including depression scales and clinical global impression scales. For each study the best available depression measure was taken as the index measure of depression outcome. Predetermined criteria were established to assist in the ranking of measures. Where authors reported categorical outcomes we calculated individual and pooled odds ratios for the odds of improvement in treated compared with control subjects. For continuous outcomes pooled effect sizes were calculated as the number of standard deviations by which the change in depression scores for the treatment group exceeded those for the control groups. Twelve studies fulfilled the criteria for inclusion in the review, eight from which dichotomous outcome data could be extracted, and eleven from which continuous outcome data could be extracted. Pooled odds ratios calculated from the dichotomous data indicated no advantage of treatment over placebo for children or adolescents (odds ratio = 0.83, 95% confidence interval 0.48 to 1.42). Effect size calculations from the continuous data suggested a statistically significant but small benefit of treatment over placebo in reducing symptoms for the aggregate sample (effect size = -0.38, 95% confidence interval -0.74 to -0.02) with subgroup analyses suggesting a larger benefit among adolescents (effect size = -0.59, 95% confidence interval -1.12 to -0.06), and no benefit among children (effect size = 0.15, 95% confidence interval -0.34 to 0.64). Treatment with a tricyclic antidepressant caused more vertigo (odds ratio = 8.47, 95% confidence interval 1.40 to 51.0), orthostatic hypotension (odds ratio = 4.77, 95% confidence interval 1.11 to 20.49) and dry mouth (odds ratio = 5.19, 95% confidence interval 1.15 to 23.51) than did placebo, but there was no statistically significant difference in other possible adverse effects. Data suggest tricyclic antidepressants are of unlikely benefit in the treatment of depression in pre pubertal children. There is marginal evidence to support the use of tricyclic antidepressants in the treatment of depression in adolescents, although the magnitude of effect is likely to be moderate at best.