Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability.
Open accessAbstract
OBJECTIVE--To examine the evidence for using selective serotonin reuptake inhibitors instead of tricyclic antidepressants in the first line treatment of depression. DESIGN--Meta-analysis of 63 randomised controlled trials comparing the efficacy and acceptability of selective serotonin reuptake inhibitors with those of tricyclic and related antidepressants. MAIN OUTCOME MEASURES--Improvement in mean scores on Hamilton depression rating scale for 53 randomised controlled trials. Pooled drop out rates from the 58 trials which reported drop out by treatment group. RESULTS--Among the 20 studies reporting standard deviation for the Hamilton score no difference was found in efficacy between serotonin reuptake inhibitors and tricyclic and related antidepressants (standardised mean difference 0.004, 95% confidence interval -0.096 to 0.105). The difference remained insignificant when the remaining 33 studies that used the 17 item and 21 item Hamilton score were included by ascribing weighted standard deviations. The odds ratio for drop out rate in patients receiving serotonin reuptake inhibitors compared with those receiving tricyclic antidepressants was 0.95 (0.86 to 1.07). Similar proportions in both groups cited lack of efficacy as the reason for dropping out but slightly more patients in the tricyclic group cited side effects (18.8% v 15.4% in serotonin reuptake group). CONCLUSIONS--Routine use of selective serotonin reuptake inhibitors as the first line treatment of depressive illness may greatly increase cost with only questionable benefit.
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Psychotropic medication is not always effective, nor is it acceptable to many patients.
“while psychotropic medication has a role to play in treating mood disorders, it is not always effective, nor is it acceptable to many patients [12].”
From An exploratory mixed methods study of the acceptability and effectiveness of mindfulness -based cognitive therapy for patients with active depression and anxiety in primary care (2006) · cites this paper as [12]
The Acceptability to Patients section reports that about one-third of patients dropped out of antidepressant trials, commonly citing lack of efficacy or side effects. This supports the point for antidepressants used in major depression, but the paper does not establish it for psychotropic medication or mood disorders generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA recent network meta-analysis for major depressive disorder showed that treatment discontinuation for mirtazapine is similar to placebo.
“A recent network meta-analysis for major depressive disorder showed that treatment discontinuation for mirtazapine is similar to placebo [15]”
From Pharmacological treatments for generalised anxiety disorder: A systematic review and network meta-analysis (2019) · cites this paper as [15]
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Efficacy of Drug Treatment in Obsessive–Compulsive Disorder: a Meta-Analytic Review
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“The question of equal efficacy compared to TCA has been addressed in a large number of studies and, recently, meta-analyses of these have been published which report equal efficacy between SSRIs and TCAs (Kasper, Fuger and Moller, 1992; Song et al., 1993).”
BackgroundResultGloss, D. S., & Vickrey, B. G. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009270.pub3 · Cited by 239 · see citing works
Peretti, S., Judge, R., & Hindmarch, I. (2000) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2000.tb10944.x · Cited by 236 · see citing works
Adverse Reactions of Selective Serotonin Reuptake Inhibitors
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“[1,2] Nevertheless, adverse reactions of SSRIs cover a broad spectrum ranging from mild gastrointestinal symptoms to severe, although rare, events, such as seizures,[3] hyponatraemia,[4] and the serotonin syndrome.”
BackgroundJönsson, B., & Bebbington, P. (1994) · The British Journal of Psychiatry · doi:10.1192/bjp.164.5.665 · Cited by 222 · see citing works
Problems and Limitations in Conducting Systematic Reviews
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“, ences for depression outcomes have implications for nefazodone, venlafaxine) have comparable clinical individual patient and physician decision-making on efficacy (Stark and Hardison, 1985; Potter et al., selection of antidepressant treatment and for the 1991; Song et al., 1993; Workman and Short, 1993; economic eva…”
BackgroundMeta-analysis: Unresolved issues and future developments
Smith, G. D., & Egger, M. (1998) · BMJ · doi:10.1136/bmj.316.7126.221 · Cited by 175 · see citing works
“…trial participants taking selective serotonin uptake inhibitors and those taking conventional antidepressants as an indicator of therapeutic success 15 : patients who stop taking their treatment because of inefficacy or side effects are the ones who are not benefiting, and thus the class of drug…”
BackgroundAparicio, L. V. M., Guarienti, F. A., Razza, L. B., Carvalho, A. F., Fregni, F., & Brunoni, A. R. (2016) · Brain stimulation · doi:10.1016/j.brs.2016.05.004 · Cited by 178 · see citing works
“This definition has indeed been adopted in past (27) and recent meta-analyses published in major journals (e.”
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Hotopf, M. H., Hardy, R., & Lewis, G. (1997) · The British Journal of Psychiatry · doi:10.1192/bjp.170.2.120 · Cited by 142 · see citing works
The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis
Mittmann, N., Herrmann, N., Einarson, T. R., Busto, U. E., Lanctôt, K. L., Liu, B. A., Shulman, K. I., Silver, I., Naranjo, C. A., & Shear, N. H. (1997) · Journal of Affective Disorders · doi:10.1016/s0165-0327(97)00107-9 · Cited by 135 · see citing works
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Problems in the Design and Reporting of Trials of Antifungal Agents Encountered During Meta-analysis
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Efficacy of newer medications for treating depression in primary care patients
Mulrow, C. D., Williams, J. W., Chiquette, E., Aguilar, C., Noël, P. H., Lee, S., Cornell, J. E., & Stamm, K. E. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00316-2 · Cited by 128 · see citing works
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Quality Improvement Research on Late Life Depression in Primary Care
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“It could be speculated that the anxiolytic and antidepressant actions of FLV might have contributed to the reduction of eating concerns, and of subsequent restraint over eating. Similarly to FLX, FLV did not provide any additional benefit on depressive symptoms when compared to CBT alone.Comparing FLX and FLV in addit…”
ResultAntidepressants for anorexia nervosa
Claudino, A. M., de Lima, M. S., Hay, P. P., Bacaltchuk, J., Schmidt, U. H., & Treasure, J. L. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004365.pub2 · Cited by 116 · see citing works
Antidepressant Treatment of Depression: A Metaanalysis
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“The favorable safety profile of the SSRIs was in large part responsible for their acceptance as the first-line therapy for the treatment of depression (Edwards and Anderson, 1999; Ferguson, 2001; Song et al., 1993).”
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Raising Questions about Antidepressants
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“Because the preponderance of the evidence suggests that SSRIs in general, and fluoxetine in particular, have similar efficacy (Greenberg, Bornstein, Zborowski, Fisher, & Greenberg, 1994) and overall dropout rates when compared to tricyclic antidepressants (Anderson & Tomenson, 1995; Song et al., 1993 ), the tricyclic…”
ResultComparative Tolerability Profiles of the Newer versus Older Antidepressants
Rudorfer, M. V., Manji, H. K., & Potter, W. Z. (1994) · Drug Safety · doi:10.2165/00002018-199410010-00003 · Cited by 106 · see citing works
Selective serotonin reuptake inhibitors (SSRIs) versus other antidepressants for depression
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Self-citationRetractedLieberman, J. A., Greenhouse, J. B., Hamer, R. M., Krishnan, K. R. R., Nemeroff, C. B., Sheehan, D. V., Thase, M. E., & Keller, M. B. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300571 · Cited by 105 · see citing works
“Premature attrition results in the loss of outcome data from as many as 30% (Anderson and Tomenson, 1994; Hotopf et al, 1997; Montgomery et al, 1994; Song et al, 1993) of the subjects enrolled in an RCT.”
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Are SSRIs a Cost-Effective Alternative to Tricyclics?
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Depression and Congestive Heart Failure
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“Most clinical trials of different antidepressants generally show equal efficacy (Effective Health Care Bulletin, 1993; Anderson and Thomenson, 1994; Song et al., 1994).”
BackgroundPrescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide
Freemantle, N., House, A. O., Song, F., Mason, J. M., & Sheldon, T. (1994) · BMJ · doi:10.1136/bmj.309.6949.249 · Cited by 100 · see citing works
Self-citationA comparison of methods for adaptive sample size adjustment
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Pharmacology of the Selective Serotonin Reuptake Inhibitors in Children and Adolescents
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Fleck, M. P. D. A., Berlim, M. T., Lafer, B., Sougey, É. B., Porto, J. A. D., Brasil, M. A. A., Juruena, M. F., & Hetem, L. A. (2009) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462009000500003 · Cited by 101 · see citing works
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Diretrizes da Associação Médica Brasileira para o tratamento da depressão (versão integral)
Fleck, M. P. D. A., Lafer, B., Sougey, É. B., Porto, J. A. D., Brasil, M. A. A., & Juruena, M. F. (2003) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462003000200013 · Cited by 97 · see citing works
Non-hormonal Systemic Medications and Dry Eye
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“For example, similarities among antidepressants in regard to clinical effectiveness and adverse effects are much more striking than their differences [9], and previous reviews have combined antidepressant classes [10].”
BackgroundResultRecent developments in the pharmacotherapy of mood disorders.
Thase, M. E., & Kupfer, D. J. (1996) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.64.4.646 · Cited by 94 · see citing works
The Antidepressant Web: Marketing depression and making medicines work
Medawar, C. (1997) · International Journal of Risk and Safety in Medicine · doi:10.3233/jrs-1997-10203 · Cited by 92 · see citing works
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Recursive Cumulative Meta-analysis
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Absenteeism Among Employees Treated for Depression
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Antidepressants and suicide mortality
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Mental Health Policy and Psychotropic Drugs
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“Three metaanalyses in the 1990s found SSRIs and TCAs to be of comparable efficacy, but the SSRI treatments had significantly lower rates of patient dropout during the clinical trials (Anderson and Tomenson 1994; Le Pen et al. 1994; Montgomery et al. 1994; Song et al. 1993).”
BackgroundResultEpidemiology and Relative Toxicity of Antidepressant Drugs in Overdose
Henry, J. A. (1997) · Drug Safety · doi:10.2165/00002018-199716060-00004 · Cited by 82 · see citing works
Drugs versus placebo for dysthymia
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RetractedEffects of Antidepressant Treatment on the Quality of Daily Life
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“A fairly frequent use of hypnotics could also explain an unexpected low rate of sleep disorders and possibly the low drop-out rate (7).”
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“Selective serotonin reuptake inhibitors (SSRIs) have been demonstrated to be effective for the treatment of depression and present fewer concerns over cardiotoxicity as they lack anticholinergic effects and reports of rhythm disturbances have been rare [70–73].”
BackgroundThe need for treatment evidence for common mental disorders in developing countries
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“Recent meta-analyses of antidepressants, for example, included not a single study from a developing country (Song et al. 1993; Hotopf et al. 1997).”
BackgroundSerotonin transporters: Implications for antidepressant drug development
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Paroxetine: safety and tolerability issues
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Guidelines, enthusiasms, uncertainty, and the limits to purchasing
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“It is also possible, though difficult, to stop purchasing one treatment or diagnostic technique when two are of equal effectiveness but different cost; when less effective treatment is more expensive”
BackgroundFamily interventions in schizophrenia
Anderson, J., & Adams, L. (1996) · BMJ · doi:10.1136/bmj.313.7056.505 · Cited by 73 · see citing works
“Perhaps this reflects resource issues—while no formal economic evaluation of family intervention for schizophrenia exists, the large number needed to treat (seven families for a year) to prevent one relapse suggests that the intervention is highly labour intensive. But this conclusion became available only with the pr…”
BackgroundAntidepressant use in clinical practice: efficacy v. effectiveness
Donoghue, J., & Hylan, T. R. (2001) · The British Journal of Psychiatry · doi:10.1192/bjp.179.42.s9 · Cited by 72 · see citing works
- Authors
- Song, F., Freemantle, N., Sheldon, T. A., House, A., Watson, P., Long, A., & Mason, J.
- Affiliations
- University of Leeds (GB)
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 1993-03-13
- Volume
- 306
- Issue
- 6879
- Pages
- 683-687
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- OpenAlex
- W2052223361
- Cited by
- 399
- References
- 85
- Citations by year
- 2025: 3 · 2023: 2 · 2021: 3 · 2019: 10 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 11
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- selective serotonin reuptake inhibitors, tricyclic antidepressants, depression, treatment efficacy, treatment acceptability, treatment discontinuation, adverse effects, cost-effectiveness
- MeSH terms
- Antidepressive Agents, Tricyclic, Depressive Disorder, Humans, Patient Dropouts, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, Treatment Outcome, Patient Satisfaction, Selective Serotonin Reuptake Inhibitors
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