Who develops severe or fatal adverse drug reactions to selective serotoninreuptake inhibitors?

Objective: To ascertain the risk factors associated with the development of severe and fatal adverse drug reactions (ADRs) or intentional overdoses by patients on selective serotonin reuptake inhibitors (SSRIs). Methods: We undertook a data analysis of Health Canada's database of Advers e Drug Reactions to SSRIs from 1986 to 1996 as well as a literature review. Results: Among the complete ADR reports in? the SSRI database there were no sex differences iii occurrences of all ADRs (n = 1011), severe ADRs (n = 2 95, drug-drug interactions (n = 312), deaths (n = 87), or intentional overd oses (n = 79), when sex differences in prescription practices were consider ed. There were no differences in ADR rates among different SSRIs. The most common cause of death among patients taking SSRIs was intentional overdose (n = 65, 74.7%). This was reported in 47 (72.3%) women and 18 (27. 7%) men. The most common drugs taken with SSRIs in patients who died of int entional overdoses were benzodiazepines, tricyclic antidepressants (TCAs), narcotics, alcohol and diphenhydramine. Patients who had severe or fatal AD Rs were more likely to be taking an SSRI with 2 or more other drugs, includ ing alcohol Drug combinations that included another CYP-450 drug were espec ially problematic. A total of 129 cardiovascular ADRs were reported, most of which were severe , These included rhythm disturbances, blood pressure perturbations, and che st pain or angina. Cardiovascular ADRs mast often occurred with concomitant drug use of benzodiazepines, TCAs, histamine H-2 antagonists, lithium, and calcium channel blockers. There were 3 deaths from malignant neuroleptic s yndrome unassociated with intentional overdose. Conclusions: SSRIs are relatively safe when their widespread use is compare d with the prevalence of ADRs. SSRIs may, however he associated with ADRs, and even death, following intentional overdose or when taken with 2 or more other drugs or alcohol (particularly another drug metabolized by CYP-450). Physicians prescribing SSRIs need to consider drug-drug interactions and c arefully monitor patients with severe affective disorders, comorbid medical conditions (especially cardiovascular disease), alcohol abuse, or a histor y of overdosing.