By: Dr. Frank MacMillan – March, 2016
Acid or proton-pump inhibitor drugs (PPI) are among the most widely prescribed medicines in the world. They include brand names such as Nexium, Dexilant, Prilosec, Protonix, and generics such as omeprazole and pantoprazole. The first medicines in this class of drugs were first available in the late 1980s. They are amazingly effective in relieving heartburn, healing stomach and duodenal ulcers by reducing the production of stomach acid, thereby allowing the acid related injury to heal. They work very well, so well that they have largely replaced the older H2 blocker class which included Tagamet, Zantac and Pepcid. These 1970s drugs were big blockbusters when they were introduced, completely changing the way we approached ulcer disease from crippling surgery to almost exclusively well-tolerated and highly effective medical therapy. Just think about it. The proton-pump inhibitor class introduced in the late 1980s blew away the previous generation medications that altered the natural history of disease, and saved and improved countless lives in the process. Both classes have been prescribed billions of times and have proved to be remarkably well tolerated and safe, or so we thought.
As a specialist in gastroenterology, I have found these medications to be very useful, and also very forgiving with a virtual lack of side effects and remarkable reliability. Many of the patients that I see are already on these medications from other prescribers before I have met them. As useful as these medications are, they are so well tolerated that they are sometimes too easily given to anyone complaining of any kind of upper abdominal discomfort. These medications are even available over the counter or prescribed with only a cursory history, physical examination, and limited formulation of an adequate differential diagnosis. I will often see a patient for the reason that the drugs are “not working.” These drugs are so effective, that if they are “not working,” then there is almost always another problem present that is undiagnosed or not being treated. These drugs treat acid, period. If acid is causing your heartburn, you will get relief. If acid is causing an ulcer, it will heal and you will be relieved of any acid related ulcer pain. The problem that we have is that there are lots of things that cause pain which are not acid related. So the drugs “fail” if your yardstick of efficacy is the relief of pain. I would suggest that the problem is something else and needs further investigation.
I see many people already taking these medications, often for many months or even years. When I was a resident physician, and for those who do not already know that almost all medical schools are affiliated with a Veterans Affairs Medical Center, we used to call these meds, “VA vitamins,” because we never met a vet who was not taking them. Now it is entirely reasonable to give someone a two-week trial of these medicines when they present with an upper abdominal complaint of pain, burning or distress. The problem is that the med gets started, and they often get continued and refilled without much further thought because they have almost no immediate side effects. My point is that these medications are so over-prescribed, that there are literally millions of people taking these meds without a good reason, and they don’t even know it.
Let me say it again, you can buy these medicines over the counter, and even without a prescription. I do however get asked to prescribe these medications for reasons of insurance coverage. I believe that the request is appropriate, especially if the medicine is prescribed for more than a few weeks or a few months. For those who I prescribe regularly, I usually make sure they have an endoscopy to be certain that we know exactly what we are treating, and I also make sure they see me at least once a year.
Over the past twenty years that I have been a licensed physician, concerns have been raised about the potential for side effects from these drugs. I will remind you that literally multiple billions of prescriptions have been made over thirty years with minimal reports of adverse effects, but there is no drug that poisons something (acid pumps in this case), that does not have an effect somewhere else that is unexpected. Over many years, concerns have been raised about osteoporosis as a side effect. I tell my patients that the association is weak, but to take vitamin D and calcium. There was also a reported association with Clostridium dificile colitis. This is an infection that occurs in patients generally on antibiotics and in hospitals. Not a major concern for most. More recently however, there has been an association with acute and chronic kidney disease. I think there may actually be something real here. Those most at risk are those who have other risks for chronic kidney disease, including diabetes and hypertension. I have exactly one patient among many thousands who had to discontinue his medicine due to low magnesium levels. He’s doing fine by the way.
In the most recent issue of JAMA Neurology, there was a study from Germany published that noted an association with dementia (loss of memory, senile, Alzheimer’s disease). They looked at 73,000 patients retrospectively, mostly women over age 75, and records were reviewed from 2004-2011. The researchers identified 2950 patients as chronic PPI users and looked for repeated PPI prescriptions over at least an 18-month period to identify the population at risk. They found that 29,510 people of the 73,000 developed dementia over the study period. The important finding was that those who used PPI medications were 44% more likely to have developed dementia, than those who did not use chronic PPI medication as defined by the study. The study was not designed to evaluate whether some people were at increased risk to start with, though an accompanying editorial by Dr. Lewis Kuller from the University of Pittsburg noted that previous studies noted that PPI use among older women was also associated with obesity, arthritis, and other risks for dementia as well.
So the conclusion is that PPI use and dementia may be influenced by similar risk factors. Since we do not know for sure if PPI medicine contributes to or causes dementia, my best advice would be to consult with your doctor as to whether you really need to be on this medication or not. For those with severe erosive acid reflux disease, Barrett esophagus, complicated esophagitis with stricture (narrowing that interferes with swallowing), or complicated ulcer disease, the benefits of medicine will almost certainly outweigh the risks. On the other hand, if you are treating heartburn because you are overweight, or consume too much alcohol, or smoke too much, or overeat before bedtime, you need to take a serious look at whether you want to expose yourself to the uncertainty of kidney disease and dementia in taking these medicines, or rather make some positive lifestyle choices for your own benefit. Almost every medicine poisons something. Be as certain as possible that the benefits outweigh risks before you put something into your body that may also cause harm.