Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization's adverse drug reactions database and discussion of potential mechanisms.

RATIONALE: Several case-reports suggest that the use of quinolones may increase the risk of psychiatric adverse reactions such as suicidal behaviors.

OBJECTIVES: The aim of this study is to investigate whether there is a safety signal for quinolone-related suicidal behaviors in a global adverse drug reactions database.

METHODS: All antibiotic-related adverse reactions were extracted from VigiBase, the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. Disproportionality analyses were performed to investigate the association between reports of suicidal behavior and exposure to quinolones, in comparison with other antibiotics.

RESULTS: From December 1970 through January 2015, we identified 992,097 antibiotic-related adverse reactions. Among them, 608 were quinolone-related suicidal behaviors including 97 cases of completed suicides. There was increased reporting of suicidal behavior (adjusted reporting odds ratios [ROR] 2.78, 95 % CI 2.51-3.08) with quinolones as compared to other antibiotics. Candidate mechanisms for quinolone-induced suicidal behaviors include GABAA antagonism, activation of NMDA receptors, decreased serotonin levels, oxidative stress, and altered microRNA expressions.

CONCLUSIONS: We found a strong safety signal suggesting an increased risk of suicidal behaviors associated with quinolone use. Plausible psychopharmacological mechanisms could underlie this association. Further investigations are urgent to confirm and better understand these findings.