Clozapine and gastro-oesophageal reflux disease (GORD) - an investigation of temporal association.
OBJECTIVE
To establish the temporal relationship between prescription of acid-suppressant therapy, GORD and clozapine prescribing.


METHODS
In this retrospective cohort study, we identified out-patients prescribed clozapine and other atypical antipsychotics (AAP) and compared times and rates of prescribing of acid-suppressant therapy. Odds ratios were calculated.


RESULTS
Of 352 patients on clozapine and 358 patients on other AAP, there were 74 (21.0%) and 23 (6.7%) patients prescribed acid-suppressant therapy respectively [OR = 3.9 (95% CI: 2.4-6.4) P ≤ 0.0001]. In 67 of 74 cases (90.5%) vs. 18 of 23 cases (81.8%), acid-suppressant therapy began after the start of the antipsychotic. Clozapine patients were more likely to be prescribed acid-suppressant therapy within the first 5 years of initiation than those on other AAP (P = 0.039). Where indication for acid-suppressant therapy was known, it was prescribed for GORD in 44 of 62 (71.0%) of the clozapine patients and 6 of 13 (46.2%) of those on other AAP (P = 0.109). Rate of known GORD was 44 of 352 (12.5%) for clozapine and 6 of 358 (1.7%) for other atypicals [OR = 8.4 (95% CI: 3.5-19.9) P ≤ 0.0001].


CONCLUSIONS
Clozapine was associated with higher rates of GORD and acid-suppressant therapy prescribing than other AAP. There was a clear temporal relationship between the prescribing of clozapine and the later use of acid-suppressant therapy. These observations strongly suggest that prescription of clozapine was associated with the onset of GORD.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
M
M
van Veggel
O
O
Olofinjana
G
G
Davies
D
D
Taylor
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005764:Gastroesophageal Reflux / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
D000897:Anti-Ulcer Agents; D014150:Antipsychotic Agents; D003024:Clozapine