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Long-Term Use of PPIs May Lead to Dependency

Jul 7, 2009 | Parker Waichman LLP

Prilosec, Prevacid, Nexium, Protonix and other stomach acid reducers that belong to a  class of drugs known as Proton Pump Inhibitors (PPIs) could lead to dependency if taken at prescription strength over an extended period of time, new research suggests.  According to a report on, researchers at Copenhagen University have found that healthy adults without symptoms of acid reflux who took PPIs developed symptoms of the disorder when they stopped taking them after 8 weeks.

The study, which was published in the journal Gastroenterology, involved 120 healthy adults.  According to, half of the subjects took 40 milligram doses of Nexium for 8 weeks, and a placebo for the final four weeks of the trial.  The other half took a placebo for the entire 12 weeks.

At the beginning of the trial, participants in both groups reported similar gastrointestinal  symptoms.  But in weeks 9 through 12, 44% of those who had been taking Nexium reported increased symptoms, while in the placebo-only group, only 15% reported increased symptoms. By the end of the 12 week trial, despite being off Nexium for four weeks, 22% of those in that group still reported symptoms, while less than 2% in the placebo only group were reporting similar symptoms.

According to the researchers, all study participants did report that symptoms had stopped three months after Nexium treatment had ended.

According to, the researchers theorized that this "rebound"  effect was likely a response to the acid suppression caused by Nexium that  resulted in an overproduction of the stomach acid-stimulating hormone gastrin.    The effect  likely lasts between four weeks and three months, they said.  

Despite this effect, the researchers said that the benefits of PPIs outweigh the risks for those who need them.  However, according to, they expressed concern that the drugs are being overprescribed, and said doctors need to be more selective about how PPIs are prescribed.

PPIs are taken by millions of people - according to, it is estimated that 5% of adults in developed countries take the acid-reducing drugs.   But PPIs have been the subject of safety concerns.  As we've reported previously, a recent Canadian study of PPIs and osteoporosis-related fractures revealed a link between long-term PPI use and increased risk for hip, wrist, or spine fractures. We also reported in May  that Plavix  users were warned by the Society for Cardiovascular Angiography and Interventions (SCAI) to avoid PPIs following stent implantation because the combination increases the risks for heart attack (by 70 percent), stroke (48 percent), and other cardiovascular problems (repeat heart procedures by 35 percent).  And most recently, we reported on a Canadian study that found a connection between  routine prescription of PPIs during hospitalizations and  an increased risk—30 percent—of acquiring pneumonia.

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