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Tricyclic antidepressants for depressive disorders in children and adolescents: a meta-analysis of randomized-controlled trials |
Maneeton N, Srisurapanont M |
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Authors' objectives To determine the efficacy and acceptability of tricyclic antidepressants (TCAs) in the treatment of depressive disorders in children and adolescents.
Searching MEDLINE was searched from 1966 to October 1999, and the Cochrane Controlled Trials Register from 1980 to October 1999, using the following search strategy: ('antidepressive-agent', 'amitriptyline', 'amoxapine', 'clomipramine', 'desipramine', 'doxepine', 'imipramine', 'maprotiline', 'mianserine', 'nortriptyline', 'protriptyline' or 'trimipramine') and ('child*' or 'adolescent*') and ('depressive disorder' or 'depression'). The reference lists of all identified papers, and that of a previous meta-analysis, were also examined.
Study selection Study designs of evaluations included in the reviewOnly randomised controlled trials (RCTs) with a duration of at least 4 weeks were eligible for inclusion. All of the included studies appear to have been placebo-controlled.
Specific interventions included in the reviewTrials of any orally administered TCAs were eligible for inclusion in the review. The TCAs actually included were amitriptyline, desipramine, imipramine and nortriptyline.
Participants included in the reviewChildren or adolescents with depressive disorders were included in the review, whilst those with treatment-resistant depression were excluded. No demographic or further details were available.
Outcomes assessed in the reviewNonresponse was taken as a measure of efficacy. Response or nonresponse was assessed according to a number of different scales across the primary studies. The drop-out rate was used as a measure of tolerability.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality The authors do not state that they assessed validity.
Data extraction Two authors extracted the data independently. The categories of data extracted were: author, duration of study treatment, definition of response, and results.
Methods of synthesis How were the studies combined?The studies were combined by a meta-analysis. The odds ratios (ORs) for the nonresponse and drop-out rates of each trial, along with 95% confidence intervals (CIs), were computed using the method of Fleiss (see Other Publications of Related Interest no.1). The pooled response rate and nonresponse rate ORs, along with 95% CIs, were calculated using the Mantel-Haenszel fixed-effect model. A random-effects model (see Other Publications of Related Interest no.2) was used if there was evidence of significant heterogeneity.
How were differences between studies investigated?The chi-squared test for heterogeneity was applied, using a p-value of 0.05 to indicate significant heterogeneity.
Results of the review Nine placebo-controlled RCTs (n=330) met the inclusion criteria.
Nonresponse rates (9 trials): for the comparison of TCAs versus placebo, the pooled OR was 0.92 (95% CI: 0.57, 1.47; chi-squared 5.70, d.f.=8, p=0.68). Drop-out rates (5 trials): for the comparison of TCAs versus placebo, the pooled OR was 2.14 (95% CI: 1.12, 4.09; chi-squared 4.73, d.f.=4, p=0.32).
Authors' conclusions TCAs were not more effective, and may be less acceptable, than placebo in the treatment of depressive disorders in children and adolescents. However, selective serotonin re-uptake inhibitors and newer antidepressants for the treatment of these patients should be further investigated.
CRD commentary This review addressed an appropriate question with well-defined inclusion and exclusion criteria. The literature search was limited to only two databases and only English language articles appear to have been included in the review. It is possible, therefore, that the review is subject to publication bias. No validity assessment was performed. It was unclear whether the data were extracted by two independent reviewers and, if so, how any disagreements were resolved.
Although only placebo-controlled RCTs were included, the lack of information regarding whether or not the included studies were double-blind hampered the interpretation of the review's findings. Furthermore, only very limited details of the primary studies were included in the review. The meta-analysis used to pool the studies was appropriate. The authors' conclusions were supported by the data and analysis presented in the review.
Implications of the review for practice and research Practice: The authors state that the current evidence indicates that TCAs are not more effective, and may be less acceptable, than placebo in the treatment of depressive disorders in children and adolescents.
Research: The authors state that future studies should investigate the use of selective serotonin re-uptake inhibitors and newer antidepressants in the treatment of depressive disorders in children and adolescents.
Bibliographic details Maneeton N, Srisurapanont M. Tricyclic antidepressants for depressive disorders in children and adolescents: a meta-analysis of randomized-controlled trials. Journal of the Medical Association of Thailand 2000; 83(11): 1367-1374 Other publications of related interest 1. Fleiss JL. Statistical methods for rates and proportions. 2nd ed. New York: Wiley; 1981. 2. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Antidepressive Agents, Tricyclic /therapeutic use; Child; Depressive Disorder /drug therapy; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Serotonin Uptake Inhibitors /therapeutic use AccessionNumber 12001003710 Date bibliographic record published 31/05/2002 Date abstract record published 31/05/2002 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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