PPIs, although they are one of the most commonly prescribed drug classes, have been shown to have several adverse effects when used long-term. While effective in the short term, the general recommendation is only to use PPIs long-term for more severe cases. A recent study published in Neurology showed there was an association between long-term PPI use and the risk of dementia, although causality was not established.
What are PPIs?
Proton-pump inhibitors (PPIs) are a class of drugs primarily used for treating acid-related disorders such as esophagitis, non-erosive reflux disease, peptic ulcer disease, and more. They are among the most commonly prescribed medication classes in the United States. The PPI drug omeprazole (brand name Prilosec) is one of the top 10 most prescribed medications. This particular PPI is prescribed most often, possibly due to its lower cost, but most PPIs have been shown to work similarly.
Short-term PPI use is effective for many conditions, and some patients may be prescribed them to be used long-term. However, numerous studies have demonstrated that long-term use can cause various adverse effects. Because of this research, most guidelines suggest limiting long-term use and being careful about utilizing PPIs when they are not needed.
PPIs work by decreasing acid production in the stomach. They may take a few days to start working effectively. Typically they are taken before a meal to maximize their effectiveness, as this is when proton pumps are activated. Different forms are also made that prevent premature activation by gastric acid, such as enteric-coated tablets, gelatin capsules, and coated granules as a suspension.
Risk of Dementia
In this analysis, it was found that those who used PPIs for over 4 years were at a 33% higher risk of developing dementia. These patients, who were all over 45, were taken from the Atherosclerosis Risk in Communities (ARIC) study.
The link is theorized to be related to the disruption of vitamin B12 absorption and its effects on gut bacteria. Problems with B12 levels have been associated with cognitive decline. In addition, when gut bacteria levels are dysregulated, it can also affect the gut-brain connection associated with neuroinflammation. This link is speculation and has not been established clearly in the research yet. More research is needed to determine if there is a definite causation between long-term PPI use and the incidence of dementia.
In a secondary analysis, it was found that PPI use was also associated with a greater risk of dementia than with the use of H2Ras. Histamine type-2 receptor antagonists (H2 Blockers) are another class of medications used for treating similar conditions to PPIs.
Short-term use of PPIs refers to a treatment course of 4 to 8 weeks. Chronic use of PPIs has been linked to numerous health conditions. This includes stroke, cardiovascular disease, chronic kidney disease, and dementia. Even though the FDA does not approve long-term PPI use, it is still common to see patients using them for years.
Articles
Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study – Neurology
Atherosclerosis Risk in Communities (ARIC) Study – Johns Hopkins Bloomberg School of Public Health