Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.
OBJECTIVE
Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications.


METHODS
A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom.


RESULTS
There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .023), week 11 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .009), and week 12 (1.3 +/- 1.2 vs 1.0 +/- 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported > or = 1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001).


CONCLUSIONS
PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.
Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark.
Christina
C
Reimer
Bo
B
Søndergaard
Linda
L
Hilsted
Peter
P
Bytzer
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004415:Dyspepsia / Q000139:chemically induced* / Q000378:metabolism; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000139:chemically induced* / Q000378:metabolism; D006356:Heartburn / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012016:Reference Values; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D054328:Proton Pump Inhibitors; D064098:Esomeprazole