Reimer C, Søndergaard B, Hilsted L, Bytzer P. Gastroenterology. 2009;137(1):80-7.

OBJECTIVES: 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.

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 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).

CONCLUSION: 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.