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July 2, 2009 -- Proton pump inhibitors are highly effective treatments for acid reflux symptoms, but taking prescription-strength dosages of the drugs for just a few months can lead to dependency, new research suggests.
Healthy adults in the study with no history of acid reflux symptoms -- such as chronic heartburn, indigestion, or acid regurgitation -- developed such symptoms when they stopped taking the drugs after eight weeks of treatment.
The findings provide the best evidence yet that withdrawal from acid-blocking proton pump inhibitor (PPI) therapy is associated with a clinically meaningful increase in acid production above pre-treatment levels, researchers say.
PPIs like Aciphex, Prilosec, Prevacid, Nexium, and Protonix are among the most widely used prescription medications in the world. By one estimate, 5% of adults in developed countries take the acid-reducing drugs.
"We have known for years that long-term treatment with PPIs induces a temporary increase in the secretion of acid, but the thinking has been that this probably wasn't clinically relevant," lead researcher Christina Reimer, MD, of Copenhagen University tells WebMD.
Reimer and colleagues recruited 120 healthy adults with no history of acid reflux disease for the study.
Half the study participants were treated with daily 40 milligram doses of the PPI Nexium for eight weeks, followed by four weeks on a placebo. The rest took a placebo pill throughout the 12-week trial.
Each week, the participants completed a standardized questionnaire designed to rate the severity of gastrointestinal (GI) symptoms.
Although symptoms were similar in the two treatment groups at the start of the study, a big difference in symptoms was seen in the weeks after the active treatment group stopped taking the PPI.
In the PPI group, 44% reported at least one acid-related symptom in weeks nine through 12, compared to 15% of the placebo group.
By week 12, when the PPI group had been off active treatment for four weeks, about 21% reported symptoms of heartburn, indigestion, or acid regurgitation, compared to slightly less than 2% of those who never took a PPI.
The study appears in the July issue of the journal Gastroenterology.
Calls to study participants three months after PPI treatment was stopped confirmed that these symptoms had resolved, Reimer says.
"We don't know how long this rebound effect lasts, but we can say that it is somewhere between four weeks and three months," she says.
This rebound is theorized to the result of an overproduction of the stomach acid-stimulating hormone gastrin in response to PPI-related acid suppression.
When the medication is stopped, the extra gastrin in the blood signals the stomach to work overtime to produce acid. When gastrin levels return to normal, acid secretion slows, writes Reimer.
She adds that the benefits of PPI treatment still appear to far outweigh the risks for patients with established acid reflux disease.
"Most patients with acid reflux disease need an acid-suppressing drug and they should not be concerned about this," she says. "But millions of people are prescribed these drugs for uncertain indications and in these patients we run the risk of inducing the symptoms that these drugs are used to treat."
PPI researcher Kenneth McColl, MD, of the University of Glasgow, tells WebMD that the drugs are now widely prescribed for a host of upper GI complaints even though there is little evidence that they are effective for these uses.
"It is clear that doctors need to be more selective in prescribing these drugs," he says. "They should not be given to patients with upper GI symptoms on the off chance that the symptoms are acid related."
In response to the study, a spokesman for AstraZeneca Pharmaceuticals, which markets Prilosec and Nexium, questioned the study design and its relevance to patients with acid reflux symptoms.
"This study was conducted in healthy volunteers, and the authors acknowledge that they can't be sure that the conclusion can be carried over to patients who have started PPI therapy because of dyspeptic symptoms," Blair Hains tells WebMD.
Hains cited a 2007 review of research examining rebound acid hypersecretion, which concluded that there was not strong evidence that withdrawal from PPIs is associated with a clinically relevant increase in acid production.
Calls to Takeda Pharmaceuticals, which manufacturers Prevacid, were not returned by publication time.
SOURCES: Reimer, C. Gastrointerology, July 2009; vol 137: pp 80-87. Christina Reimer, MD, investigator, department of medical gastroenterology, Copenhagen University, Denmark. Kenneth E. L McColl, MD, dvision of cardiovascular and medical sciences, University of Glasgow, Scotland. Mel Wilcox, MD, gastroenterologist, University of Alabama School of Medicine, Birmingham. "Over-Prescribing PPIs," BMJ 2008. Blair Hains, spokesman, AstraZeneca Pharmaceuticals. Hunfeld, N.G. Alimentary Pharmacology & Therapeutics, 2007.
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