Neuropsychiatric Events Associated with the Use of Helicobacter Pylori Eradication Therapy Containing-Clarithromycin: Self-Controlled Case Series

Abstract

Background: There have been concerns that clarithromycin might be associated with neuropsychiatric events in many case reports and spontaneous reports from the World Health Organization and the Food and Drug Administration. Nevertheless, no observational study has been conducted to examine this association.

Objectives: To investigate the association between the use of Helicobacter pylori therapy containing‐clarithromycin and acute neuropsychiatric events.

Methods: Using the Clinical Data Analysis and Reporting System database in Hong Kong, we identified patients who had both exposure of at least one out‐patient H. pylori therapy containing‐clarithromycin and outcomes of interest during the study period from 2003‐2012 in a self‐controlled case series study. The primary outcome was composite neuropsychiatric events while secondary outcomes were psychotic events and cognitive impairment. The observation period started from one year after patients entered the database and was censored at the earliest of end of study, death, date of receiving clarithromycin script or in‐patient H. pylori therapy containing‐clarithromycin. Several risk periods were defined as 14 day pre‐exposure, day 1‐14 and day 15‐30 since prescription start date. Age adjusted incidence rate ratios were estimated using the conditional Poisson regression.

Results: The preliminary findings showed that 1824, 354 and 726 patients were identified with a first recorded composite neuropsychiatric event, psychotic event and cognitive impairment respectively within the study period. The increased incidence rate ratios of 4.12 (95% confidence interval 2.94 to 5.76), 5.42 (2.77‐10.60) and 2.63 (1.36‐5.09) were found during current use for outcomes of composite neuropsychiatric events, psychotic events and cognitive impairment respectively. However, no increased risk was found during all other risk periods for all outcomes.

Conclusions: This study showed a short‐term increased risk of neuropsychiatric events associated with H. pylori therapy containing‐clarithromycin among Hong Kong population. There was no evidence of a long‐term increased risk of neuropsychiatric events.