Lines of Evidence on the Risks of Suicide with Selective Serotonin Reuptake Inhibitors

• Published in: Psychotherapy and psychosomatics Vol. 72; no. 2; pp. 71 - 79
• Main Author: Healy, David
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.03.2003; Karger
• Subjects: Antidepressive Agents - adverse effects; Biological and medical sciences; Depressive Disorder - drug therapy; Depressive Disorder - psychology; Drug toxicity and drugs side effects treatment; Humans; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Risk Factors; Serotonin Uptake Inhibitors - adverse effects; Special Article; Suicide - statistics & numerical data; Selective serotonin reuptake inhibitors; Depression; Risk-benefit ratios; Suicidality; Antidepressants; Social environment; Agitation; Psychotropic; Toxicity; Mental health; Review; Cost benefit analysis; Reuptake inhibitor; Suicide; Epidemiology; Metaanalysis; Dose activity relation; Antidepressant agent; Public health; International; Mood disorder; Human; Healthy subject; Serotonin; Controlled therapeutic trial; Suicide attempt; Chemotherapy; Treatment; Randomized design; Risk factor; Typology; Suicide ideation; Comparative study
• ISSN: 0033-3190; 1423-0348
• DOI: 10.1159/000068691

Background: There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. Methods: Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue. Results: The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals. Conclusions: The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.