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.
Reimer
Christina
C
Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark.
Søndergaard
Bo
B
Hilsted
Linda
L
Bytzer
Peter
P
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