The Association between Acute Neuropsychiatric Events And The Use Of Helicobacter Pylori Eradication Regimen Containing-Clarithromycin

Clarithromycin is used as a part of standard Helicobacter Pylori eradication regime (HPT). However, many published case reports and spontaneous reports from the adverse drug monitoring programs of the World Health Organization (WHO) and the Food and Drug Administration (FDA) suggested the possible link between clarithromycin and acute neuropsychiatric (NP) events. Therefore, we aimed to investigate whether there is such a temporal association.

With the use of data from the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong, a self-controlled case series (SCCS) study was conducted. The SCCS was developed for eliminating time-invariant confounding by comparing the relative incidence within individuals who both had exposure and outcome of interest. We included subjects who were aged ≥18 at cohort entry and must had an out-patient prescription of HPT containing-clarithromycin and a first recorded outcome of interest as principal diagnosis in the accident & emergency or in-patient setting during the study period from 1st January 2003 to 31st December 2012. The primary outcome was the composite of NP events while secondary outcomes included psychotic events and cognitive impairment. The observation period started from one year after the patients entered the CDARS and was censored at the earliest of end of study, death, date of receiving clarithromycin as monotherapy or in-patient HPT. We defined three risk windows as 14 day pre-exposure, day 1-14 and day 15-30 since prescription start date. All other periods were classified as baseline periods. Age adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression.

A total of 1824, 1005 and 726 subjects who had both exposure and first recorded composite of NP events, psychotic events and cognitive impairment respectively were identified as shown in the preliminary analyses. For composite of NP events, the increased IRRs of 4.12 (95% Confidence interval (CI) 2.94 to 5.76) during day 1-14 since prescription start date was observed respectively. However, no increased risk of NP events was found during all other risk windows. Similar temporal pattern for an increased risk of psychotic events was also only observed during the risk period of day 1-14 (IRR 3.34; 95%CI 2.03 to 5.49). Similarly, an increased risk of cognitive impairment could only be found during day 1-7 since the treatment initiation (IRR 2.63; 95%CI 1.36 to 5.09). In conclusion, this study showed the evidence of a short-term risk of NP events associated with HPT containing-clarithromycin among Hong Kong population.