Do fluoroquinolones raise risk of hospital admission for suicidality?

Use of fluoroquinolones for the treatment of pneumonia or urinary tract infection (UTI) does not appear to markedly increase the risk of hospital admission or emergency department visits due to suicidality compared with azithromycin or combined trimethoprim and sulfamethoxazole, a study has shown.

“We cannot, however, exclude a small increase in risk, or an effect on suicidal thoughts that do not lead to hospital admission or emergency department visit,” the researchers said.

This population-based cohort study included 2,756,268 adults aged ≥18 years who initiated an oral fluoroquinolone (eg, ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, ofloxacin, gatifloxacin, norfloxacin, lomefloxacin, besifloxacin) or comparator antibiotic between January 2003 and September 2015 and had at least 6 months of continuous health plan enrolment and a diagnosis of pneumonia or UTI ≤3 days before the drug initiation date.

Comparator antibiotics used were azithromycin and trimethoprim-sulfamethoxazole in the pneumonia and UTI cohorts, respectively. The researchers matched participants 1:1 within each cohort on a propensity score, calculated from a multivariable logistic regression model that included 57 baseline covariates. Subsequently, they used Cox proportional hazard models to estimate hazard ratios (HRs) and 95 percent confidence intervals (CIs).

Of the participants, 551,042 were in the pneumonia cohort and 2,205,526 in the UTI cohort. A total of 181 events occurred in the pneumonia cohort and 966 in the UTI cohort during the 60-day follow-up. Fluoroquinolones had adjusted HRs of 1.01 (95 percent CI, 0.76‒1.36) relative to azithromycin in the pneumonia cohort and 1.03 (95 percent CI, 0.91‒1.17) versus trimethoprim-sulfamethoxazole in the UTI cohort. [BMJ 2022;379:e069931]

Consistent results were observed across sensitivity analyses and subgroups of age, sex, or history of mental illnesses.

“Despite differences in data sources and design and analysis methods, our findings are consistent with those of Jick [and colleagues’] case-control study, which compared fluoroquinolone users with antibiotic nonusers,” the researchers said. [Br J Clin Pharmacol 1998;45:77-81]

“The findings of our study, which used an active comparator design to tackle differences in individuals who did and did not use an antibiotic, bolster the findings of Jick [and colleagues’] study,” they added. [JAMA Intern Med 2020;180:1596-605]

Notably, the results of the current study must be interpreted in the context of under-reporting and selective reporting of spontaneous adverse drug events, according to the researchers. [Front Pharmacol 2020;11:428]

Several factors, including the experience of the reporter, local patterns of utilization, specificity of the adverse reaction, and knowledge about safety profile of the drug, can influence the reporting patterns of these reactions to pharmacovigilance systems, which can restrict the analysis of disproportionality studies. [Therapie 2019;74:225-232]

Fluoroquinolone use is associated with toxic effects on gastrointestinal, dermatological, cardiovascular, and nervous systems, as well as with a range of mental health side effects, among which suicidal ideation is of concern. [Expert Opin Drug Saf 2013;12:497-505; Antibiotics (Basel) 2019;8:E104; www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-updates-warnings-oral-and-injectable-fluoroquinolone-antibiotics]

“People attempting or completing suicide and suicidal ideation have been reported after initiation of fluoroquinolones,” the researchers said. [Gen Hosp Psychiatry 2011;33:82.e5-7; BMJ Case Rep 2014;2014:bcr2013201469; Gen Hosp Psychiatry 2010;32:108-110; Psychosomatics 2012;53:97-98]