Eight studies (n=138) were included in the review: 4 randomised controlled trials (RCTs; n=60) and 4 open studies (n=78).
Study quality was considered good in three studies, moderate in three and low in two.
Aspiration studies with determination of basal, maximal or peak secretory capacity. Two small RCTs (n=22 healthy participants) did not find a higher gastric acid production, while an open trial of patients with reflux oesophagitis (n=9) showed a significant increase in basal and pentagastrin-stimulated acid secretion, after the cessation of PPIs. The influence of H. pylori on gastric acid secretion after PPI was assessed in 2 open studies of healthy participants. In the first trial (n=21), basal and maximal secretory capacity at day 15 were significantly higher compared with baseline among H. pylori-negative patients, while no significant variation was observed in H. pylori-positive patients. In the second study (n=32), H. pylori-negative patients experienced an increase in maximal secretory capacity of 16 to 40% after PPI treatment cessation. In H. pylori-positive patients, basal and maximal secretory capacity were significantly higher at day 28 relative to baseline. In H. pylori-eradicated patients, secretory capacity was only increased at day 56; maximal secretory capacity was increased until day 28 after cessation. No comparisons were made between the three investigated groups.
Aspiration studies with determination of 24-hour intragastric acidity or integrated nocturnal acidity (2 studies).
In the first open study which included patients with duodenal ulcer (n=9), a lower 24-hour intragastric acidity was found at 7 days after PPI withdrawal, while similar levels were detected at 56 days. In the second study, 24 healthy men were randomised in a double-blind fashion to 300 mg ranitidine or 40 mg omeprazole for 25 days. A significant increase in integrated nocturnal acidity was observed at 3 and 6 days after ranitidine withdrawal in the patients allocated to omeprazole withdrawal; integrated nocturnal activity returned to pre-treatment levels by day 6 after PPI withdrawal. The patients receiving omeprazole had higher gastrin levels on the last day of dosing compared with pre-treatment values.
Studies using intragastric pH monitoring.
In a randomised controlled double-blind trial which included 16 healthy patients, a similar intragastric pH was found at days 4, 7 and 14 after placebo or lansoprazole withdrawal. Serum gastrin levels increased significantly during therapy, returning to pre-treatment levels in all the study participants within 14 days after therapy discontinuation.