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Cited by 351Treatment of Major DepressionMental Health Treatment and AccessAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis

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Arroll, B.·2005·The Annals of Family Medicine
DOI 10.1370/afm.349PMC PMC1466912
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Abstract

PURPOSE: Depression is common in primary care. There are no systematic reviews of depression treatment comparing antidepressants with placebo; hence, we do not know whether these medications are effective in primary care. METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Group register of controlled trials, MEDLINE, International Pharmaceutical abstracts, PsycINFO, and EMBASE. Abstracts of potential studies were reviewed independently by 2 authors. Studies needed to include randomized controlled trials of either a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI), or both, and placebo in a primary care setting. The data and quality of the studies were extracted and assessed by 2 authors blind to the other's choice. Disagreements were resolved by discussion. The main outcome measures were the standardized mean difference and weighted mean difference of the final mean depression scores, the relative risk of improvement, and the number withdrawing because of side effects. Pooling of results was done using Review Manager 4.2.2. RESULTS: There were 10 studies in which TCAs were compared with placebo, 3 in which SSRIs were compared with placebo, and 2 with both compared with placebo. One half of the studies were of low methodological quality, and nearly all studies were of short duration, typically 6 to 8 weeks. Pooled estimates of efficacy data showed a relative risk of 1.26 (95% CI, 1.12-1.42) for improvement with TCAs compared with placebo; For SSRIs, relative risk was 1.37 (95% CI, 1.21-1.55). Most patients, 56% to 60%, responded well to active treatment compared with 42% to 47% for placebo. The number needed to treat for TCAs was about 4, and for SSRIs it was 6. The numbers needed to harm (for withdrawal caused by side effects) ranged from 5 to 11 for TCAs and 21 to 94 for SSRIs. Low-dose (100 mg or 75 mg) as well as high-dose TCAs were effective. CONCLUSION: This systematic review is the first comparing antidepressants with placebo for treatment of depression in primary care. Both TCAs and SSRIs are effective. This review is also the first to show that low-dose TCAs are effective in primary care. Prescribing antidepressants in primary care is a more effective clinical activity than prescribing placebo.

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  • In the general population, selective serotonin reuptake inhibitors (RR for improvement 1.37; 95%CI 1.21, 1.55) and tricyclic antidepressants (RR for improvement 1.26; 95%CI 1.12, 1.42) can be effective in improving depression compared to placebo.

    “In the general population, selective serotonin reuptake inhibitors (SSRIs) (relative risk (RR) for improvement: 1.37; 95%CI: 1.21, 1.55) and tricyclic antidepressants (RR for improvement: 1.26; 95%CI: 1.12, 1.42) can be effective in improving depression when compared to placebo (Arroll et al., 2005”

    From Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis (2016) · cites this paper as Arroll et al., 2005

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  • Currently approved treatments for major depressive disorder (MDD), including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), effectively reduce MDD symptoms.

    “Currently approved treatments for major depressive disorder (MDD), including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), effectively reduce MDD symptoms (Arroll et al., 2005;Cipriani et al., 2009).”

    From Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (2016) · cites this paper as Arroll et al., 2005

    The Discussion (page not provided) concludes that SSRIs are more effective than placebo, and the Results report improvement in studies whose participants all had MDD. The meta-analysis covers SSRIs and tricyclic antidepressants in primary care, not SNRIs, so it does not support the SNRI part of the claim. (LLM, conf=0.88)

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Cites

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Research works printed but not linked: 8

  1. Suh T, Gallo JJ. The management of depression among general medical service providers. Psychol Med. 1999;27:1051-1063.
  2. Cochrane Collaboration Depression Anxiety and Neurosis Review Group. Available at: http://www.cochrane.org.
  3. Ellis PM, Smith DA. Treating depression: the beyond blue guidelines for treating depression in primary care. Med J Aust. 2002;176:S77-S83.
  4. Philipp M, Kohnen R, Hiller KO. Hypercium extract versus imipramine or placebo in patients with moderate depression: randomised multi- centre study of treatment for eight weeks. BMJ. 1999;319:1534-1539.
  5. Feighner JP, Brauzer B, Gelenberg AJ, et al. A placebo-controlled mulitcenter trial of limbitrol versus its components amitriptyline and chlordiazepoxide. Psychopharmacol. 1979;61:217-225.
  6. Lecrubier Y, Bourin M, Moon CA, et al. Effi cacy of venlafaxine in depressive illness. Acta Psychiatr Scand. 1997;95:485-493.
  7. Brink CW, vdKrogt JP, Dunbar GC, Behagel LH. A controlled clinical trial of mianserin and placebo in the treatment of depression in gen- eral practice. J Drug Ther Res. 1984;9:513-517.
  8. Williams JW, Mulrow CD, Chiquette E, Noel PH, Acaster C, Cornell J. a systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med. 2000;132:743-756.

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Authors
Arroll, B.
Affiliations
University of Auckland (NZ)
Corresponding author
Arroll, B.
ORCID
Arroll, B.
Venue
The Annals of Family Medicine
Publisher
Annals of Family Medicine
Published
2005-09-01
Volume
3
Issue
5
Pages
449-456
ISSN
  • 1544-1709 (ISSN-L)
  • 1544-1717
DOI
10.1370/afm.349
PMC
PMC1466912
OpenAlex
W2121920106
Cited by
351
References
40
Citations by year
2026: 8 · 2025: 5 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 21 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 19 · 2016: 31 · 2015: 21 · 2014: 16 · 2013: 20 · 2012: 18
FWCI
2.33
Type
journal article
Language
en
Open access
Locations
  • The Annals of Family Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, cc-by)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, other-oa)
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, tricyclic antidepressants, selective serotonin reuptake inhibitors, antidepressant efficacy, antidepressant tolerability, placebo comparison, primary care, adverse effects, number needed to treat, number needed to harm, treatment response, antidepressant discontinuation, depression scores
MeSH terms
Antidepressive Agents, Tricyclic, Depressive Disorder, Humans, Placebos, Primary Health Care, Placebo Effect, Randomized Controlled Trials as Topic, Selective Serotonin Reuptake Inhibitors

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