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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Efficacy and safety of antidepressants for children and adolescents

JN Jureidini, CJ Doecke, PR Mansfield, MM Haby, DB Menkes, and AL Tonkin.

Review published: 2004.

CRD summary

This review assessed the quality and reporting of trials of newer antidepressant drugs for children. The new drugs were associated with a small benefit, which may have been exaggerated, and some serious adverse effects, which may have been downplayed. Many details of the methods used in the review were not reported, but the conclusions seem valid.

Authors' objectives

To review the efficacy and safety of antidepressants in children by assessing the quality of the methods used and the reporting of trials.


MEDLINE (from 1989 to February 2004), EMBASE (from 1988 to 2004, week 04) and PsycLIT (from 1985 to February, week 3 2004) were searched; the search terms were listed.

Study selection

Study designs of evaluations included in the review

Only randomised controlled trials (RCTs) were eligible for inclusion in the review.

Specific interventions included in the review

Inclusion criteria for the intervention were not stated. The included studies assessed paroxetine, fluoxetine, sertraline and venlafaxine, compared with placebo or with tricyclic antidepressants (imipramine).

Participants included in the review

Inclusion criteria for the participants were not stated. However, it is clear that studies of children with depression were eligible for inclusion in the review. The participants in the included studies were aged from 6 to 20 years.

Outcomes assessed in the review

Inclusion criteria for the outcomes were not stated. The outcomes reported in the review were the adverse effects of treatment, and study withdrawals and scores on the revised children's depression rating scale (from one study only). The outcomes reported in the included studies were:

global (clinical global impression score, response, children's global assessment scale);

depression (children's depression rating scale-revised, remission, Hamilton Depression Rating Scale, Raskin depression scale, children's depression inventory, schedule for affective disorders and schizophrenia for adolescents);

anxiety (Covi anxiety scale, multidimensional anxiety scale for children);

brief psychiatric rating scale for children;

child behaviour checklist;

self-perception profile;

autonomous function checklist;

sickness impact scale;

paediatric quality of life enjoyment and satisfaction;

Weinberg screening assessment scale; and

Hopkins symptom checklist.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The validity criteria were not listed in the paper. The authors discussed the following: trial funding; whether the outcomes were clinician, patient or parent rated; the follow-up period; the reporting of adverse events; withdrawals; whether trials used intention-to-treat analysis; the use of categorical versus continuous outcomes; blinding; and clinical significance of the findings. The authors did not state how the papers were assessed for validity, or how many reviewers performed the validity assessment.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Data were extracted on the primary outcome measures and 'other' outcome measures (with corresponding significance values), as reported in the individual studies. To derive estimates of efficacy, 'relevant' outcome measures were averaged within studies and the standardised mean difference (Hedge's g) was chosen as the measure of effect.

Data were also extracted on the funding of trials, adverse effects of treatment, study methodology and the quality of the reported data. Study methodology covered study withdrawals, the use of categorical outcomes, unblinding and clinical implications of statistical superiority to placebo.

Methods of synthesis

How were the studies combined?

For efficacy data, the standardised mean differences from each study were pooled using a random-effects model. All continuous outcome measures related to depression and health-related quality of life were included.

Data on the funding of trials, adverse effects of treatment, study methodology and the quality of the reported data were presented narratively.

How were differences between studies investigated?

The authors did not state how differences between the studies were investigated.

Results of the review

Six RCTs (n=1,036) were included in the review.

Study methods.

High withdrawal rates were seen in all six studies; these ranged from 17 to 32% in the selective serotonin re-uptake inhibitor group and from 17 to 46% in the placebo group. Most of the studies used an intention-to-treat analysis. Three of the six nominated primary outcomes in the included studies were categorical variables created from continuous variables (categorical variables can inflate small differences between groups). None of the included studies gave any data on the effectiveness of blinding.

Quality of reporting.

There were some issues around the quality of reporting, including authors exaggerating the benefits and downplaying the harms.


Pharmaceutical companies paid for the trials and otherwise funded the authors of at least three of the four larger studies.

A meta-analysis of the five published studies of selective serotonin reuptake inhibitors resulted in a small effect size of 0.26 (95% confidence interval: 0.13, 0.40).

Adverse treatment effects. In one trial, 11 of 93 patients on paroxetine had serious adverse events compared with 2 of the 87 patients in the placebo group (P=0.01). In another trial, 17 of the 189 patients on sertraline withdrew because of adverse events compared with 5 of the 184 patients in the placebo group (P=0.01).

Authors' conclusions

Investigators' conclusions on the efficacy of newer antidepressants for childhood depression have exaggerated the beneficial effects of such antidepressants. Strong improvement was seen in placebo groups; additional benefit from drugs is of doubtful clinical significance. Adverse effects of newer antidepressants have not been emphasised. Antidepressant drugs cannot be recommended with confidence as a treatment option for childhood depression. A more critical approach to assess the validity of published data is required.

CRD commentary

Many methodological details of this review were missing. Study inclusion criteria relating to the interventions, participants and outcomes of interest were not stated explicitly, nor were criteria for the validity assessment, although some aspects of validity were discussed in detail. Details of the review process (how many reviewers selected studies, assessed validity and extracted the data) were not reported. The search strategy was reported for the electronic databases, but it was not reported whether other sources (e.g. reference lists) were used or whether any language restrictions were applied. The authors did search for unpublished studies but did not include these in their meta-analysis. The meta-analysis undertaken seems appropriate, but it is not possible to be sure as the included outcomes were not reported and the authors did not discuss whether any investigation of heterogeneity within the included studies was undertaken. The authors' conclusions are based mostly on a critique of the methodological validity of the included studies, and follow from what is stated in the review paper.

Implications of the review for practice and research

Practice: The authors stated that antidepressant drugs cannot be recommended with confidence for the treatment of childhood depression.

Research: The authors stated that a more critical approach to ensuring the validity of published data is needed.

Bibliographic details

Jureidini J N, Doecke C J, Mansfield P R, Haby M M, Menkes D B, Tonkin A L. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004; 328: 879-883. [PMC free article: PMC387483] [PubMed: 15073072]

Indexing Status

Subject indexing assigned by NLM


Adolescent; Antidepressive Agents /adverse effects /therapeutic use; Child; Clinical Trials as Topic /economics /methods /standards; Humans; Patient Dropouts; Research Support as Topic; Treatment Outcome



Database entry date


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.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15073072