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.

Method:  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].

Conclusion:  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.