title: Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin.
abstract: There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events.
  
  
  
  To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events.
  
  
  
  A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin.
  
  
  
  The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression.
  
  
  
  Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis.
  
  
  
  This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin.
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Angel Y S
authors.initials: AY
authors.lastname: Wong
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China2Research Department of Practice and Policy, School of Pharmacy, University Colleg.
authors.forename: Ian C K
authors.initials: IC
authors.lastname: Wong
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Celine S L
authors.initials: CS
authors.lastname: Chui
authors.affiliation: Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Edwin H M
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: W C
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Eric Y H
authors.initials: EY
authors.lastname: Chen
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wai K
authors.initials: WK
authors.lastname: Leung
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000890:Anti-Infective Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D017291:Clarithromycin / Q000009:adverse effects*; D003693:Delirium / Q000453:epidemiology / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000453:epidemiology; D016480:Helicobacter pylori / Q000187:drug effects; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage; D008875:Middle Aged; D010045:Outpatients; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D011618:Psychotic Disorders / Q000453:epidemiology / Q000209:etiology*; D012893:Sleep Wake Disorders / Q000453:epidemiology / Q000209:etiology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D017291:Clarithromycin