CRD summary

The authors concluded that remission rates are highest and drop-out rates are lowest with serotonin-norepinephrine re-uptake inhibitors compared with selective serotonin re-uptake inhibitors and tricyclic antidepressants, suggesting that they are clinically superior for treating major depression. These conclusions should be treated with caution as they are not based on comparisons of treatments within trials.

Authors' objectives

To compare rates of remission, drop-outs and adverse drug reactions (ADRs) between three classes of drugs used for treating major depressive disorder (MDD): serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).

Searching

MEDLINE, EMBASE, International Pharmaceutical Abstracts and the Cochrane Library were searched from 1980 to December 2005; some search terms were reported. No language restrictions were applied.

Study selection

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Two reviewers independently extracted the data and resolved any disagreements on inclusion through consensus. For each study, the number of patients successfully and unsuccessfully treated, the numbers of drop-outs and completers, remission rates and drop-out rates (both with 95% confidence intervals, CIs) were presented for each drug treatment arm.

Methods of synthesis

Results of the review

Fifteen RCTs (n=2,458) were included. These studies provided 30 treatment arms. Ten studies (n=836) evaluated SNRIs, 11 studies (n=916) evaluated SSRIs and 9 studies (n=706) evaluated TCAs.

Significant statistical heterogeneity was found for all three drug classes for remission and drop-out rates. The authors could find no apparent explanations for this heterogeneity.

Patients in the TCA and SNRI treatment arms were significantly older than patients in the SSRI treatment arms (53.7 and 52.5 years, respectively, versus 40.9 years, p<0.05). Patients in the SSRI treatment arms were significantly heavier than patients in the TCA treatment arms (75.4 kg versus 62.6 kg, p<0.05).

Remission rates: ITT analysis.

Patients in the SNRI and TCA treatment arms had significantly higher rates of remission than patients in the SSRI treatment arms (49% and 44.1%, respectively, versus 37.7%, p<0.001 for both comparisons). There was no significant difference between the SNRI and TCA treatment arms. Remission rates varied within each drug class: from 31 to 70% within the SNRI treatment arms, from 19 to 70% within SSRIs, and from 23 to 54% within TCAs.

Remission rates: per protocol analysis.

TCAs were associated with significantly higher rates of remission than SNRIs and SSRIs (69% versus 64% and 54%, respectively, p<0.001 for both comparisons). There was no significant difference between the SNRI and SSRI treatment arms.

Drop-out rates.

ITT analysis: patients in the TCA treatment arms had significantly higher drop-out rates than patients in the SSRI and SNRI treatment arms (35.7% versus 28.4% and 26.1%, respectively, p<0.05 for both comparisons). There was no significant difference between the SNRI and SSRI treatment arms.

Drop-outs due to ADRs were significantly higher in the TCA treatment arms than in the SNRI and SSRI treatment arms (19.8% versus 10.3% and 8.3%, respectively, p<0.05).

There was no significant difference between the three drug classes for drop-outs due to loss of efficacy.

ADRs.

Patients in the TCA treatment arms had the highest rates of occurrence for most selected ADRs, including dry mouth (58%), sweating (28%) and constipation (26%).

The authors stated that the funnel plot suggested the presence of publication bias but the Begg-Mazumdar test found no strong evidence for it.

Authors' conclusions

Remission rates are highest and drop-out rates are lowest with SNRIs compared with SSRIs and TCAs, suggesting that they are clinically superior for the treatment of major depression.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and study design. However, it is not clear why only RCTs were eligible given that the analyses were not based on within-study treatment comparisons. Several relevant sources were searched and no language restrictions were imposed. No attempts to minimise publication bias were reported, although the authors did assess the potential for it and found no convincing evidence of major bias. Methods were used to minimise reviewer error and bias in the study selection and data extraction processes. Adequate details of the included studies were presented. The majority of the studies were of relatively short duration, with most lasting 8 weeks. The studies were pooled using meta-analysis and statistical heterogeneity was found for all three drug classes. Meta-analysis graphs were not presented but inspection of the tables showed variation within drug classes and the overall results for the drug class may not reflect treatment effects of individual drugs; the authors did mention this. Conclusions regarding the relative effects of different antidepressant drug classes were not based on direct comparisons of treatments within trials. Any conclusions drawn about the relative effects of SSNRIs, SSRIs and TCAs are not, therefore, definitive.

Implications of the review for practice and research

Practice: The authors stated that clinical information about the specific drug and results from well-designed comprehensive pharmacoeconomic analysis should be taken into account when deciding on the most appropriate drug. Research: The authors stated that there is a need for an economic analysis based on data presented in this review.

Bibliographic details

Machado M, Iskedjian M, Ruiz I, Einarson T R. Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Current Medical Research and Opinion 2006; 22(9): 1825-1837. [PubMed: 16968586]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adrenergic Uptake Inhibitors /adverse effects /therapeutic use; Antidepressive Agents, Tricyclic /adverse effects /therapeutic use; Depressive Disorder, Major /drug therapy /psychology; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Remission, Spontaneous; Serotonin Uptake Inhibitors /adverse effects /therapeutic use

AccessionNumber

12006007408

Database entry date

31/03/2008

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.