Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose.
BACKGROUND
Self-poisoning is a common method of suicide and often involves ingestion of antidepressants. Information on the relative toxicity of antidepressants is therefore extremely important.


OBJECTIVE
To assess the relative toxicity of specific tricyclic antidepressants (TCAs), a serotonin and noradrenaline reuptake inhibitor (SNRI), a noradrenergic and specific serotonergic antidepressant (NaSSA), and selective serotonin reuptake inhibitors (SSRIs).


METHODS
Observational study of prescriptions (UK), poisoning deaths involving single antidepressants receiving coroners' verdicts of suicide or undetermined intent (England and Wales) and non-fatal self-poisoning episodes presenting to six general hospitals (in Oxford, Manchester and Derby) between 2000 and 2006. Calculation of fatal toxicity index based on ratio of rates of deaths to prescriptions, and case fatality based on ratio of rates of deaths to non-fatal self-poisonings.


RESULTS
Fatal toxicity and case fatality indices provided very similar results (rho for relative ranking of indices 0.99). Case fatality rate ratios showed greater toxicity for TCAs (13.8, 95% CI 13.0-14.7) than the SNRI venlafaxine (2.5, 95% CI 2.0-3.1) and the NaSSA mirtazapine (1.9, 95% CI 1.1-2.9), both of which had greater toxicity than the SSRIs (0.5, 95% CI 0.4-0.7). Within the TCAs, compared with amitriptyline both dosulepin (relative toxicity index 2.7) and doxepin (2.6) were more toxic. Within the SSRIs, citalopram had a higher case fatality than the other SSRIs (1.1, 95% CI 0.8-1.4 v. 0.3, 95% CI 0.2-0.4).


CONCLUSIONS
There are wide differences in toxicity not only between classes of antidepressants, but also within classes. The findings are relevant to prescribing decisions, especially in individuals at risk, and to regulatory policy.
Hawton
Keith
K
Centre for Suicide Research, University of Oxford, Department of Psychiatry, Warneford Hospital, Headington, Oxford OX3 7JX, UK. keith.hawton@psych.ox.ac.uk
Bergen
Helen
H
Simkin
Sue
S
Cooper
Jayne
J
Waters
Keith
K
Gunnell
David
D
Kapur
Navneet
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000506:poisoning*; D002648:Child; D062787:Drug Overdose / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004739:England / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D013405:Suicide / Q000706:statistics & numerical data*; D014852:Wales / Q000453:epidemiology; D055815:Young Adult
D000928:Antidepressive Agents