Suicide and self-harm following prescription of SSRIs and other antidepressants: Confounding by indication

Research Unit, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 12/2005; 60(5):519-25. DOI: 10.1111/j.1365-2125.2005.02480.x
Source: PubMed


To identify the incidence and risk of suicide and self harm, among patients prescribed antidepressant drugs.
A retrospective cohort study, with nested case control, of patients identified from a nonrandom sample of general practices in New Zealand from 1996 to 2001. A total of 57 361 patients who received a prescription for a single antidepressant were identified from the RNZCGP Research Unit Database. Suicides within 120 days of a prescription were identified from the New Zealand National Mortality Database and self-harm events within 120 days of a prescription were identified from the New Zealand Hospital discharge database.
26 suicides and 330 episodes of self-harm were identified within 120 days of an antidepressant prescription. On univariate analysis the association, expressed as OR (95% CI), between selective serotonin reuptake inhibitors (SSRIs) and self harm and suicide were 2.26 (1.27-4.76) and 1.92 (0.77-4.83), respectively. When corrected for the confounding effects of age, gender and depression/suicidal ideation there was an association between SSRIs and self harm, OR 1.66 (95% CI 1.23-2.23), but not for suicide, 1.28 (0.38-4.35). Paroxetine was a significant risk factor for suicide on univariate analysis, 4.23 (1.19-14.95), but not when corrected for age, gender and depression/suicidal ideation, 2.76 (0.30-24.87).
Age, gender and pre-existing depression/suicidal ideation are important confounders in observational studies of the association between antidepressants and suicide or self harm.

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    • "Our study also has several limitations. Several studies have demonstrated that patients with a greater risk of suicide or self-harm (often with a recorded history of self-harm) are preferably prescribed SSRIs, since this antidepressant class is safer when taken in overdose than TCAs (Didham et al., 2005; Mandour, 2012). As the number of history of self-harm cases in our study was low, it is likely that we were not able to extract all cases of self-harm prior to start of therapy. "
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    ABSTRACT: The existing literature provides contradictory evidence on antidepressant use and risk of suicide. Some studies have shown that the use of Selective Serotonin Reuptake Inhibitors (SSRIs) is associated with an increased risk of suicide, especially during the first months of treatment, whereas other studies did not confirm this association. For this reason, our objective was to investigate the association between antidepressant use and risk of suicide in incident antidepressant users in relation to time since starting therapy. We conducted a population-based cohort study within the Dutch Integrated Primary Care Information (IPCI) database, in incident users of antidepressant therapy between 1994 and 2012 (n=27,712). Cox proportional hazard models were used to study the association between current use of SSRIs, tricyclic antidepressants (TCA) and other antidepressants and risk of suicide or attempted suicide. During follow-up, a total of 280 incident antidepressant users attempted or committed suicide. Current use of SSRIs (hazard ratio (HR): 0.78, 95% CI: 0.57-1.07), TCAs (HR: 0.82, 95% CI: 0.48-1.42) or other antidepressants (HR: 0.75, 95% CI: 0.47-1.18) was not statistically significantly associated with suicide compared to past use of any of the antidepressants. Although a large healthcare database was used, the number of reported cases of suicide (attempt) was low. This study did not indicate an increase in risk of suicide after starting treatment with SSRIs, TCAs or other antidepressants compared with past antidepressant use. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Dec 2014 · Journal of Affective Disorders
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    • "The 2005 study for example included 26 completed suicides but the authors advise that " to determine if there is a doubling of the risk of suicide would require a sample size of 192, 436 in each treatment group. " A study of New Zealand suicide victims published by two of the same authors in the following year found " Sedatives, anxiolytics, and antidepressants were associated with suicide, with the strongest association being for sedatives " (Didham et al, 2006). "
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    ABSTRACT: A review of literature on the role of negative life events and adverse life circumstances in suicide indicates they better explain the antecedents of suicide than psychiatric disorders.
    Full-text · Article · Feb 2014
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    • "Other sources of data about this controversial topic include large cohorts of depressed patients from general practice or health-maintenance organizations, and relatively large, case-control comparisons of subgroups varying in exposure to antidepressants. Such studies include over one million, mainly clinically depressed, subjects in 17 reports [71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87]. These studies have yielded inconsistent findings. "
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    ABSTRACT: The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.
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