(229) Investigating Self-Poisoning in The FDA Adverse Event Reporting System: Clinical Features and Lethal Dose Estimation

Publication Number: 1274

Background: Self-poisoning with medications is the globally preferred suicidal approach, with important repercussions on both the health and the judicial system. Current investigations of the phenomenon involve only limited sample sizes and data reliability.

Objectives: We investigate the utility of the FDA Adverse Event Reporting System (FAERS) in outlining the traits and trends of drug-mediated suicidal acts and estimating lethal dose (LD).

Methods: FAERS spontaneous reports of suspected adverse drug reactions (January 2004-September 2021) were retrieved, including cases of “intentional overdose” and “poisoning deliberate”. Drug-specific case-fatality rates (CFR) were calculated for the most reported drugs. Chi-square with Holm-Bonferroni correction for multiple comparisons was used to detect significant differences between reports of self-poisoning and other reports. It was also applied within self-poisoning, to highlight differences between non-fatal and fatal cases. Temporal trends and geographical differences were assessed. Finally, the database was used for a proposal of LD estimation, fitting a binomial model to the interpolation of known doses and outcomes.

Results: We retrieved 41,103 self-poisoning cases (17% fatal). Compared to other reports, self-poisoning commonly involved young people (p=0.002: 12% vs 3% < 18 years old –yo–; 24% vs 8% 18-30yo; 36% vs 22% 30-50yo), individuals with psychiatric conditions (p < 0.001: 14% vs 6%) and alcohol consumption (p < 0.001: 5% vs 0%). Fatal cases were more commonly observed in men (p < 0.001: 45 vs 38%), older people (p=0.002: 42% vs 35% 30-50yo; 23% vs 17% 50-65yo), and alcohol exposure (p < 0.001: 9% vs 5%). Drugs implicated were mainly antidepressants (14%), analgesics (11%), and antipsychotics (10%), with paracetamol being the most reported medication in both fatal and non-fatal acts. High CFRs were observed with oxycodone (61%), bupropion (36%), diphenhydramine (35%). Geographical differences were observed, paracetamol being recorded in ≥60% self-poisoning cases in Ireland, promethazine in ≥50% in Sweden, metformin in ≥20% in Turkey. A general increase in self-poisoning reports was observed in the last two decades.
Paracetamol exposure doses were mostly < 100g, with an estimated LD25≈125g and LD50≈200g. Paracetamol’s CFR was higher when concomitant drugs were recorded (31% vs 16%).

Conclusions: The richness, timeliness, and worldwide coverage of the FAERS, along with dose information, complement already accrued knowledge about self-poisoning. The study of FAERS data could, therefore, help design regulatory interventions and promote tailored prevention measures to address the phenomenon of drug-mediated suicides.