Fluoroquinolones and the risk of panic attacks: a systematic review and disproportionality analysis using individual case safety reports from the FDA Adverse Event Reporting System (FAERS) database

BACKGROUND AND OBJECTIVES: Fluoroquinolones are linked with increased risk of CNS adverse events, such as anxiety and depression. Recently, case reports have linked fluoroquinolone use and panic attacks. However, current evidence exploring the link between fluoroquinolone use and panic attacks remains limited and requires investigation for safe use. To systematically review the literature on fluoroquinolone use and the risk of panic attacks, and to study this association by comparing fluoroquinolones with other antibiotics using the FDA Adverse Event Reporting System (FAERS) database. METHODS: MEDLINE and Embase databases were searched to identify relevant studies for systematic review. Active-comparator restricted disproportionality analyses using FAERS (2004Q1-2024Q4) were performed for ciprofloxacin, levofloxacin, and moxifloxacin compared to azithromycin and trimethoprim/sulfamethoxazole. Reporting odds ratios (ROR), proportional reporting ratios, adjusted ROR for potential confounders, and Bayesian analyses were conducted to detect safety signals for MedDRA term 'panic attack'. RESULTS: The systematic review identified 12 studies (4 clinical trials, 8 publications describing 11 case reports), with the prevalence of panic attacks ranging between 0.46% and 1.76% in trials. Disproportionality analysis showed that, compared to azithromycin, fluoroquinolones were associated with a 6-fold increase in reports of panic attacks and a 12-fold increase compared to trimethoprim/sulfamethoxazole. Results were consistent across Bayesian analyses. CONCLUSION: The findings suggest an association between fluoroquinolones and increased risk of panic attacks, underscoring the need for validation through pharmacoepidemiological studies. Due to reliance on spontaneous reports, causal relationships cannot be determined for clinical recommendations. These results offer insights for research on CNS safety profiles of fluoroquinolones.