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

Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis

A von Wolff, LP Holzel, A Westphal, M Harter, and L Kriston.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

The authors concluded that the review provided evidence of the efficacy of selective serotonin reuptake inhibitors and tricyclic antidepressants in the treatment of chronic depression. Selective serotonin reuptake inhibitors demonstrated better acceptability than tricyclic antidepressants. This was a well-conducted review. The conclusions reflect the evidence presented and are likely to be reliable.

Authors' objectives

To examine the efficacy, acceptability and comparative effectiveness of selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) in the treatment of chronic depression.

Searching

MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science were searched from 1970 to January 2010 with no language restrictions. Search terms were reported. Social Sciences and Science Citation Index and ClinicalTrials.gov were searched for further studies. Three relevant journals and reference lists of relevant studies and reviews were searched manually. First authors of all included studies were contacted regarding other trials.

Study selection

Randomised controlled trials (RCT) that included the administration of SSRI or TCA for the treatment of depressive symptoms in adults with a diagnosis of chronic major depression, dysthymia, double depression or recurrent depression without complete remission between episodes were eligible for inclusion. Diagnosis had to be based on a formal classification system. The comparator treatment needed to be either a pharmacological placebo or another antidepressant pharmacological intervention (SSRI or TCA). Only studies that reported the efficacy of the intervention were eligible for inclusion. Efficacy outcomes of interest were response to treatment (at least 50% decrease from baseline to end of treatment on a depression scale) and remission (severity score below the threshold of clinical significance at the end of treatment). Acceptance outcomes based on drop-outs and adverse events were assessed.

Fourteen studies included participants with dysthymia only. Five studies included participants with dysthymia or double depression. The other study included participants with chronic major depression or participants with chronic major depression or double depression. All studies included outpatients and two studies also included in-patients. Mean ages ranged from 34 to 69.9 years. In most studies more than 60% of participants were women. Most studies compared SSRI (sertraline, fluoxetine, paroxetine, escitalopram) or TCA (imipramine, amineptine, desipramine, dothiepin, trazodone) with placebo. Individual study doses were reported in the review. Treatment duration ranged from four to 24 weeks. Nearly half of the studies were conducted in USA.

Two reviewers independently screened studies for inclusion. Disagreements were resolved through discussion.

Assessment of study quality

Study quality was assessed with the Cochrane Collaboration Risk of Bias Tool for randomisation, allocation concealment, blinding, handling of incomplete data, selective outcome reporting and any other bias. Studies were deemed low risk if at least four of the items were met and no high risk of bias was detected. Studies were deemed high when at least three items were not met and at least one item suggested serious risk of bias. Otherwise risk of bias was defined as unclear.

Two reviewers independently assessed study quality. Disagreements were resolved through discussion

Data extraction

Efficacy and acceptance data were extracted to calculate benefit ratios (BR) and odds ratios (OR), with 95% confidence intervals (CIs), using intention-to-treat principles. Twelve weeks after the start of treatment was used as the primary endpoint. Where this was not reported outcome data between six and 18 weeks were accepted.

Two reviewers independently extracted data. Disagreements were resolved through discussion

Methods of synthesis

Outcomes were pooled using the DerSimonian and Laird random-effects model. Statistical heterogeneity was assessed using the Q and Ι² statistics. Subgroup analyses were performed by diagnosis and study quality for the outcomes response and dropouts. Numbers needed to treat were also calculated.

Publication bias was assessed using the Egger’s test and through examination of the funnel plots.

Results of the review

Twenty RCTs (22 comparisons, 2,772 participants) reported in 51 publications were included in the review. Sample sizes ranged from 15 to 635. Risk of bias was evaluated as low for four studies, unclear for 10 studies and high for six studies.

SSRI versus Placebo (nine RCTs): SSRI showed significantly better response (BR 1.49, 95% CI 1.29 to 1.71; Ι²=0%) and remission (BR 1.53, 95% CI 1.29 to 1.80; Ι²=0%) outcomes compared to placebo. There were no significant differences for drop-outs and adverse events. Statistically significant heterogeneity was identified for drop-outs (Ι²=52%)

TCA versus Placebo (seven RCTs): TCA showed significantly better response (BR 1.74, 95% CI 1.50 to 2.02; Ι²=0%) and remission (BR 1.77, 95% CI 1.24 to 2.53; Ι²=51%) outcomes compared to placebo. Statistically significant heterogeneity was identified for remission. Adverse events were significantly higher in the TCA group compared to the placebo group (OR 2.87, 95% CI 1.83 to 4.50; Ι²=20%). There were no significant differences between TCA and placebo for drop-outs.

SSRI versus TCA (six RCTs): There was no statistically significant difference between SSRI and TCA for response or remission. SSRI showed significantly lower drop-out (OR 0.41, 95% CI 0.19 to 0.86; Ι²= 71%) and adverse event (OR 0.48, 95% CI 0.32 to 0.70; Ι²= 1%) outcomes compared to TCA. Statistically significant heterogeneity was identified for drop-outs.

Subgroup analysis showed no significant differences for any outcomes between types of diagnosis (TCA studies only). Only one comparison showed a statistically significant difference between studies with an unclear or high risk of bias compared with a low risk of bias (this included only one study judged to have low risk of bias).

No indication for publication bias was identified using the Egger's test and visual examination of funnel plots.

Authors' conclusions

The review provides evidence of the efficacy of SSRI and TCA in the treatment of chronic depression. SSRI demonstrated better acceptability than TCA in terms of drop-outs and adverse events.

CRD commentary

The review question and inclusion criteria were clearly defined. The authors used multiple sources to identify published and unpublished studies and there were no language restrictions, which minimised risks of language and publication biases. Steps were taken to minimise the likelihood of error and bias during study selection, data extraction and quality assessment. Appropriate methods were used to assess study quality and the results of this assessment, and other pertinent study details, were included in the review. Appropriate methods were used to pool the results.

This was a well conducted review. The conclusions reflect the evidence presented and are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that SSRI seem to be the first choice for the treatment of chronic depression. Clinicians may also consider patients’ personal needs and drug tolerance.

Research: The authors stated that further research on cost effectiveness, long-term outcomes and patient-related outcomes in treating chronically depressed patients was required.

Funding

Bundesministerium für Bildung und Forschung, Germany.

Bibliographic details

von Wolff A, Holzel LP, Westphal A, Harter M, Kriston L. Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis. Journal of Affective Disorders 2012; 144(1-2): 7-15. [PubMed: 22963896]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Antidepressive Agents, Tricyclic /therapeutic use; Chronic Disease; Depressive Disorder /drug therapy; Dysthymic Disorder /drug therapy; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Serotonin Uptake Inhibitors /therapeutic use; Treatment Outcome

AccessionNumber

12012042995

Database entry date

10/04/2013

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: 22963896

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