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Cited by 265Treatment of Major DepressionMental Health Treatment and AccessAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis

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MacGillivray, Steve, Arroll, Bruce, Hatcher, Simon, Ogston, Simon, Reid, Ian, Sullivan, Frank, Williams, Brian, Crombie, Iain·2003·BMJ
DOI 10.1136/bmj.326.7397.1014PMC PMC154760
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Abstract

Objective: To compare the efficacy and tolerability of tricyclic antidepressants with selective serotonin reuptake inhibitors in depression in primary care. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: Register of the Cochrane Collaboration's depression, anxiety, and neurosis group. Reference lists of initial studies and other relevant review papers. Selected authors and experts. Selection of studies: Studies had to meet minimum requirements on: adequacy of sample size, adequate allocation concealment, clear description of treatment, representative source of subjects, use of diagnostic criteria or clear specification of inclusion criteria, details regarding number and reasons for withdrawal by group, and outcome measures described clearly or use of validated instruments. Main outcome measures: Standardised mean difference of final mean depression scores and relative risk of response when using the clinical global impression score. Relative risk of withdrawing from treatment at any time, and the number withdrawing due to side effects. Results: 11 studies (2951 participants) compared a selective serotonin reuptake inhibitor with a tricyclic antidepressant. Efficacy between selective serotonin reuptake inhibitors and tricyclics did not differ significantly (standardised weighted mean difference, fixed effects 0.07, 95% confidence interval −0.02 to 0.15; z=1.59, P<0.11). Significantly more patients receiving a tricyclic withdrew from treatment (relative risk 0.78, 95% confidence interval 0.68 to 0.90; z=3.37, P<0.0007) and withdrew specifically because of side effects (0.73, 0.60 to 0.88; z=3.24, P<0.001). Most studies included were small and supported by commercial funding. Many studies were of low methodological quality or did not present adequate data for analysis, or both, and were of short duration, typically six to eight weeks. Conclusion: The evidence on the relative efficacy of selective serotonin reuptake inhibitors and tricyclic antidepressants in primary care is sparse and of variable quality. The study setting is likely to be an important factor in assessing the efficacy and tolerability of treatment with antidepressant drugs. What is already known on this topic: Previous meta-analyses have included comparatively large numbers of secondary care based studies that indicate no significant differences in efficacy between selective serotonin reuptake inhibitors and tricyclics Previous meta-analyses are conflicting regarding the relative tolerability between selective serotonin reuptake inhibitors and tricyclics, but do suggest a small but significant difference in favour of selective serotonin reuptake inhibitors Such meta-analyses show notable heterogeneity What this study adds: Selective serotonin reuptake inhibitors are better tolerated than tricyclics by primary care patients and may be better tolerated by primary care patients than secondary care patients Study setting seems to be important and should be considered before licences are given to specific antidepressants Although there are limited high quality data, available evidence shows that the most commonly prescribed classes of antidepressants in primary care (selective serotonin reuptake inhibitors and tricyclics) are equally effective in the short term for primary care patients, but the literature has many gaps

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  • Between 27 and 31% of patients taking antidepressant medication discontinue treatment because of side effects.

    “Moreover, studies have found that between 27 and 31% of patients taking antidepressant medication discontinue treatment because of side effects (Anderson, 2000; MacGillivray et al., 2003).”

    From A mindful yoga intervention for young women with major depressive disorder: Design and baseline sample characteristics of a randomized controlled trial (2020) · cites this paper as MacGillivray et al., 2003

  • The introduction and widespread use of SSRI and psychological therapy including CBT meant that well tolerated and effective treatments for depression and anxiety disorders became available in primary care, widening the group of individuals eligible for treatment.

    “The introduction and widespread use of selective serotonine uptake inhibitors (SSRI) [22, 23] and psychological therapy including cognitive behavioral therapy (CBT) [24, 25] meant that well tolerated and effective treatments for depression and anxiety disorders became available in primary care, widening the group of individuals eligible for treatment.”

    From Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: A population-based study (2020) · cites this paper as [22]

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Authors
MacGillivray, S., Arroll, B., Hatcher, S., Ogston, S., Reid, I., Sullivan, F., Williams, B., & Crombie, I.
ORCID
Sullivan, Frank
Venue
BMJ
Publisher
BMJ
Published
2003-05-10
Volume
326
Issue
7397
Pages
1014.1
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.326.7397.1014
PMC
PMC154760
OpenAlex
W2027923042
Cited by
265
References
14
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 6 · 2015: 12 · 2014: 13 · 2013: 13 · 2012: 12
FWCI
2.42
Type
journal article
Language
en
Open access
Licence
www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
Locations
  • BMJ (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
  • Research Output (Edinburgh Napier University) (submittedVersion)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
depression, selective serotonin reuptake inhibitors, tricyclic antidepressants, antidepressant efficacy, antidepressant tolerability, treatment withdrawal, adverse effects, primary care, antidepressant comparison, treatment response, methodological quality of trials, low-quality evidence
MeSH terms
Antidepressive Agents, Tricyclic, Depressive Disorder, Humans, Patient Dropouts, Primary Health Care, Randomized Controlled Trials as Topic, Treatment Outcome, Selective Serotonin Reuptake Inhibitors

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