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Review
. 2009 Jul 8;2009(3):CD007954.
doi: 10.1002/14651858.CD007954.

Antidepressants versus placebo for depression in primary care

Bruce Arroll  1 , C Raina Elley, Tana Fishman, Felicity A Goodyear-Smith, Tim Kenealy, Grant Blashki, Ngaire Kerse, Stephen Macgillivray
Affiliations
Review

Antidepressants versus placebo for depression in primary care

Bruce Arroll et al. Cochrane Database Syst Rev. .

Abstract

Background: Concern has been expressed about the relevance of secondary care studies to primary care patients specifically about the effectiveness of antidepressant medication. There is a need to review the evidence of only those studies that have been conducted comparing antidepressant efficacy with placebo in primary care-based samples.

Objectives: To determine the efficacy and tolerability of antidepressants in patients (under the age of 65 years) with depression in primary care.

Search strategy: All searches were conducted in September 2007.The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) Controlled Trials Register was searched, together with a supplementary search of MEDLINE, PsycINFO, EMBASE, LILACS, CINAHL and PSYNDEX. Abstracts of all possible studies for inclusion were assessed independently by two reviewers. Further trials were sought through searching the reference lists of studies initially identified and by scrutinising other relevant review papers. Selected authors and experts were also contacted.

Selection criteria: Studies were selected if they were randomised controlled trials of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults. Older patients (over 65 years) were excluded. Patients had to be recruited from a primary care setting. For continuous outcomes the Hamilton Depression scale of the Montgomery Asberg Scale was requred.

Data collection and analysis: Data were extracted using data extraction forms by two reviewers independently, with disagreements resolved by discussion. A similar process was used for the validity assessment. Pooling of results was done using Review Manager 5. The primary outcome was depression reduction, based on a dichotomous measure of clinical response, using relative risk (RR), and on a continuous measure of depression symptoms, using the mean difference (MD), with 95% confidence intervals (CI).

Main results: There were fourteen studies (16 comparisons) with extractable data included in the review, of which ten studies examined TCAs, two examined SSRIs and two included both classes, all compared with placebo. The number of participants in the intervention groups was 1364 and in the placebo groups 919. Nearly all studies were of short duration, typically 6-8 weeks. Pooled estimates of efficacy data showed an RR of 1.24, 95% CI 1.11-1.38 in favour of TCAs against placebo. For SSRIs this was 1.28, 95% CI 1.15 to 1.43.. The numbers needed to treat (NNT) for TCAs ranged from 7 to 16 {median NNT 9} patient expected event rate ranged from 63% to 26% respectively) and for SSRIs from 7 to 8 {median NNT 7} (patient expected event rate ranged from 48% to 42% respectively) . The numbers needed to harm (NNH for withdrawal due to side effects) ranged from 4 to 30 for TCAs (excluding three studies with no harmful events leading to withdrawal) and 20 to 90 for SSRIs.

Authors' conclusions: Both TCAs and SSRIs are effective for depression treated in primary care.

PubMed Disclaimer

Conflict of interest statement

BA is a member of the Primary Care group of the Future Forum and Educational Foundation funded by AstraZeneca (UK). BA is also a member of the Pharmac seminar series board. Pharmac is the New Zealand government funding agency for pharmaceuticals. BA has also been funded to a conference by Sanofi‐Aventis.

Figures

1
1
Funnel plot of comparison: 1 TCAs versus placebo, outcome: 1.2 Clinical response at post‐treatment.
1.1
1.1. Analysis
Comparison 1 TCAs versus placebo, Outcome 1 Depression symptoms at post‐treatment.
1.2
1.2. Analysis
Comparison 1 TCAs versus placebo, Outcome 2 Clinical response at post‐treatment.
1.3
1.3. Analysis
Comparison 1 TCAs versus placebo, Outcome 3 Occurrence of adverse effects at post‐treatment.
1.4
1.4. Analysis
Comparison 1 TCAs versus placebo, Outcome 4 Withdrawal from trials at post‐treatment.
1.5
1.5. Analysis
Comparison 1 TCAs versus placebo, Outcome 5 Depression symptoms: 1‐4 week timepoints.
1.6
1.6. Analysis
Comparison 1 TCAs versus placebo, Outcome 6 Clinical response: 1‐4 week timepoints.
1.7
1.7. Analysis
Comparison 1 TCAs versus placebo, Outcome 7 Depression symptoms: dosage of TCAs.
1.8
1.8. Analysis
Comparison 1 TCAs versus placebo, Outcome 8 Clinical response: dosage of TCAs.
1.9
1.9. Analysis
Comparison 1 TCAs versus placebo, Outcome 9 Depression symptoms: UK vs USA/European‐based studies.
1.10
1.10. Analysis
Comparison 1 TCAs versus placebo, Outcome 10 Clinical response: UK vs USA/European‐based studies.
1.11
1.11. Analysis
Comparison 1 TCAs versus placebo, Outcome 11 Depression symptoms: approximated vs non‐approximated data.
1.12
1.12. Analysis
Comparison 1 TCAs versus placebo, Outcome 12 Clinical response: approximated vs non‐approximated data.
1.13
1.13. Analysis
Comparison 1 TCAs versus placebo, Outcome 13 Depression symptoms: high vs low quality studies.
1.14
1.14. Analysis
Comparison 1 TCAs versus placebo, Outcome 14 Clinical response: high vs low quality studies.
1.15
1.15. Analysis
Comparison 1 TCAs versus placebo, Outcome 15 Depression symptoms: major depression diagnosis.
1.16
1.16. Analysis
Comparison 1 TCAs versus placebo, Outcome 16 Depression symptoms: use of different depression scales.
1.17
1.17. Analysis
Comparison 1 TCAs versus placebo, Outcome 17 Clinical response: greatly improved/remission.
1.18
1.18. Analysis
Comparison 1 TCAs versus placebo, Outcome 18 Depression symptoms: 50% or more GP assessors.
1.19
1.19. Analysis
Comparison 1 TCAs versus placebo, Outcome 19 Clinical response: 50% or more GP assessors.
1.20
1.20. Analysis
Comparison 1 TCAs versus placebo, Outcome 20 Depression symptoms: studies with no competing interest.
1.21
1.21. Analysis
Comparison 1 TCAs versus placebo, Outcome 21 Clinical response: studies with no competing interest.
2.1
2.1. Analysis
Comparison 2 SSRIs versus placebo, Outcome 1 Clinical response at post‐treatment.
2.2
2.2. Analysis
Comparison 2 SSRIs versus placebo, Outcome 2 Occurrence of adverse effects at post‐treatment.
2.3
2.3. Analysis
Comparison 2 SSRIs versus placebo, Outcome 3 Withdrawal from trials at post‐treatment.
2.4
2.4. Analysis
Comparison 2 SSRIs versus placebo, Outcome 4 Clinical response: UK vs USA/European‐based studies.
2.5
2.5. Analysis
Comparison 2 SSRIs versus placebo, Outcome 5 Clinical response: high quality studies.
2.6
2.6. Analysis
Comparison 2 SSRIs versus placebo, Outcome 6 Clinical response: major depression diagnosis.
2.7
2.7. Analysis
Comparison 2 SSRIs versus placebo, Outcome 7 Depression symptoms: use of Montgomery‐Asberg scale.
2.8
2.8. Analysis
Comparison 2 SSRIs versus placebo, Outcome 8 Clinical response: use of Montgomery‐Asberg scale.
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