Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies.
Open accessAbstract
BACKGROUND: It is unclear whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressant drugs reduce the risk of suicide in people with depression. We explored the association between exposure to SSRIs and risk of suicide completion or attempt. METHODS: We conducted a systematic review of observational studies that reported completed or attempted suicide in depressed individuals who were exposed to SSRIs compared with those who were not exposed to antidepressants. We assessed the overall risk of completed or attempted suicide. RESULTS: Eight studies involving more than 200 000 patients with moderate or severe depression were included in the meta-analysis. Although exposure to SSRIs increased the risk of completed or attempted suicide among adolescents (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.51-2.44), the risk was decreased among adults (OR 0.57, 95% CI 0.47-0.70). Among people aged 65 or more years, exposure to SSRIs had a protective effect (OR 0.46, 95% CI 0.27-0.79). Sensitivity analyses did not change these findings. In particular, for studies that used completed suicide as an outcome, exposure to SSRIs was associated with increased risk among adolescents (OR 5.81, 95% CI 1.57-21.51) and decreased risk among adults (OR 0.66, 95% CI 0.52-0.83) and older people (OR 0.53, 95% CI 0.26-1.06). INTERPRETATION: Based on data from observational studies, use of SSRIs may be associated with a reduced risk of suicide in adults with depression. Among adolescents, use of SSRIs may increase suicidality.
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Barbui et al. (2009) found that the OR for the overall relationship between SSRI and suicidal behavior was 1.92 (95% CI, 1.51-2.44).
“Barbui et al. (2009) found that the OR for the overall relationship between SSRI and suicidal behavior was 1.92 (95% CI, 1.51–2.44).”
From Risk and Protective Factors of Self-harm and Suicidality in Adolescents: An Umbrella Review with Meta-Analysis (2024) · cites this paper as Barbui et al., 2009
The Adolescents results report an OR of 1.92 (95% CI 1.51–2.44), but only for adolescents, not for an overall relationship across ages. The same passage reports ORs of 0.57 for adults and 0.46 for elderly people; the Interpretation likewise says the relationship varies by age. (LLM, conf=0.92)
Experimental — accuracy not yet measuredThe observational review by Barbui et al. (2009) suggested a promoting effect of SSRI exposure among adolescents but a protective effect in adults and the elderly.
“The observational review (Barbui et al., 2009), including different age groups, suggested a promoting effect of SSRI exposure among adolescents but a protective effect in adults and the elderly.”
From Risk and Protective Factors of Self-harm and Suicidality in Adolescents: An Umbrella Review with Meta-Analysis (2024) · cites this paper as Barbui et al., 2009
The increased risk of suicidal behavior may in fact be decreased in adults.
“The increased risk of suicidal behavior reported in pediatric patients [99] does not appear to be seen in adults, and may in fact be decreased [99,100].”
From Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders (2014) · cites this paper as [99]
The increased risk of suicidal behavior reported in pediatric patients does not appear to be seen in adults.
“The increased risk of suicidal behavior reported in pediatric patients [99] does not appear to be seen in adults, and may in fact be decreased [99,100].”
From Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders (2014) · cites this paper as [99]
Three of 120 associations (2.5%) had convincing evidence: SSRI use with increased suicide attempt or completion in children and adolescents, and any antidepressant before pregnancy or SSRIs during pregnancy with autism spectrum disorder.
“Among the 120 associations, 3 (2.5%) were supported by convincing evidence, namely, the association between SSRI use and increased risk of suicide attempt or completion in children and adolescents 80 as well as the association between exposure to any antidepressant before pregnancy and SSRIs during pregnancy and autism spectrum disorder 51,52 (Table 2).”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as [80]
Nearly all significant associations showed higher risk with antidepressants; two exceptions showed SSRIs protecting against suicide attempt or completion in adults and older adults.
“Almost all statistically significant associations indicated an increased risk for antidepressants and adverse health outcomes except for 2 associations (2.7%) showing the protective property of SSRIs against suicide attempt or completion in adults and in older adults.80”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as [80]
One highly suggestive association showed a protective effect of antidepressants against suicide attempt or completion in adults.
“One association with highly suggestive evidence, however, showed a decreased risk (ie, protective association) of suicide attempt or completion in adults, 80 meeting a high-quality level based on AMSTAR 2.”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as [80]
The review found that only a few of the 74 significant associations were supported by convincing evidence in main and sensitivity analyses: elevated risk of suicide attempt or completion in those under 19 years (SSRI studies), autism risk in offspring, preterm birth, and neonatal adaptation.
“We reviewed 45 meta-analyses of observational studies and found that only a few of the 74 statistically significant associations between antidepressants and adverse health outcomes were supported by convincing evidence in the main and sensitivity analyses, namely, the association between antidepressant use and increased suicide attempt or completion in individuals younger than 19 years (SSRI studi”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as [80]
In a sensitivity analysis of class I or II evidence, the random-effects risk ratio for suicide attempt and completion in children and adolescents with any antidepressant use versus no antidepressant use, adjusted for multiple covariates, was 1.48 (95% CI, 1.29-1.71), based on 7 studies, with class I/Moderate evidence.
“RR: 1.48 | (1.29 to 1.71)”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as Barbui et al, 80 2009
In a sensitivity analysis of class I or II evidence, the random-effects odds ratio for suicide attempt and completion in adults with SSRI/non-SSRI use was 0.53 (95% CI, 0.43-0.66), based on 5 studies, with class II/High evidence.
“OR: 0.53 | (0.43 to 0.66)”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as Barbui et al, 80 2009
In a sensitivity analysis of class I or II evidence, the random-effects odds ratio for suicide attempt and completion in children and adolescents with SSRI/non-SSRI use was 1.89 (95% CI, 1.46-2.43), based on 3 studies, with class II/High evidence.
“OR: 1.89 | (1.46 to 2.43)”
From Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review (2019) · cites this paper as Barbui et al, 80 2009
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- Authors
- Barbui, C., Esposito, E., & Cipriani, A.
- Affiliations
- University of Verona (IT)
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Impact Inc.
- Published
- 2009-02-03
- Volume
- 180
- Issue
- 3
- Pages
- 291-297
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC2630355
- OpenAlex
- W2120590819
- Cited by
- 275
- References
- 64
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 17 · 2023: 6 · 2022: 9 · 2021: 20 · 2020: 17 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 17 · 2015: 16 · 2014: 20 · 2013: 17 · 2012: 18
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- selective serotonin reuptake inhibitors, antidepressants, suicide risk, suicide mortality, suicide attempts, depression, adolescents, older adults, age differences in treatment response
- MeSH terms
- Adolescent, Adolescent Behavior, Age Factors, Depression, Humans, Suicide, Confidence Intervals, Odds Ratio, Selective Serotonin Reuptake Inhibitors, Risk Assessment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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