Digestion, Age related illnesses, General, Mental Health | March 29, 2016 | Author: The Super Pharmacist
Proton pump inhibitors (PPIs) have become one of the most frequently prescribed drug classes in the world.These drugs have developed a reputation among physicians and patients as being extremely effective and safe. In fact, PPIs are now available over-the-counter without prescription in many jurisdictions.
PPIs profoundly reduce stomach acid secretion. They are the treatment of choice for peptic ulcer disease, gastritis due to chronic NSAID use, Helicobacter pylori treatment, and erosive esophagitis.
Despite being intended for use in these relatively serious conditions, PPIs are now used for less severe conditions, such as gastroesophageal reflux disease. In fact, many patients take PPIs on a constant and daily basis for gastroesophageal reflux disease, with or without the direct guidance of a physician. Moreover, between 25 to 70% of people who take PPIs do not have an appropriate reason for doing so.
While PPIs are still useful and safe for certain indications, they may pose an unwarranted risk for those who use them without a clear need to do so. This has become more concerning as new research has revealed that PPI use is related to dementia.
A potential link between PPI use and dementia began to emerge less than five years ago.
Basic science researchers showed that proton pump inhibitors increase the production of beta amyloid, which is a key protein present in patients with Alzheimer disease. Researchers could show that chronic use of PPIs could interfere with the brain’s ability to clear itself of this toxic protein, and thus potentially worsening dementia. This laboratory research was followed by clinical studies that appear to support this hypothesis.
Not only were PPIs prescribed inappropriately to people with dementia, but the drugs themselves appear to be increasing the risk of dementia.
In the largest study so far, nearly 74,000 individuals age 75 and older who were free from dementia at the start of the study were followed for five years on average. Patients who received regular PPI treatment were 44% more likely to develop Alzheimer's disease and 38% more likely to develop dementia during the study than those who are not receiving the PPI. Some authors have identified potential weaknesses in this study. For example, this increased risk of dementia could be due to polypharmacy, i.e. the use of many drugs at the same time. Likewise, the people who in the PPI-treated group had increased rates of depression and stroke, which are known causes of cognitive dysfunction. Moreover, the study did not tease apart other known risks for dementia including family history, heavy alcohol use, high blood pressure, and atherosclerosis. In other words, there may be other sources of increased dementia risk besides PPI use alone.
PPIs are also known to decrease vitamin B12 levels, and vitamin B12 deficiency is a well-known cause of cognitive disturbance. Despite these limitations, the results of this large clinical study have raised considerable concern in the medical community and among patients.
While these results are provocative, it is simply too early to suggest that PPI use contributes to dementia or Alzheimer's disease directly. Despite being a very large study, the results show a correlation, not necessarily causation. Nevertheless, these results will likely prompt further research aimed at identifying or ruling out PPIs as a cause for dementia.
Until these definitive studies are performed, it is important to consider the published results in context. First, the patients included in this cohort study were age 75 and older.
There is simply no evidence that suggests PPI use is associated with cognitive disturbances in younger individuals. Patients over the age of 75 may wish to re-evaluate whether they truly need PPIs on a daily basis.
It may be prudent for elderly individuals to limit their use of PPIs to brief periods rather than chronic use, especially if they have other risk factors for Alzheimer's disease and dementia.
Indeed, it makes sense for people of all ages to consider whether daily PPI use is indicated inappropriate. As many as three quarters of individuals take PPIs without any clear reason to do so, there is clearly room to reduce risk and use of this class of drugs.
Histamine receptor blockers, while less effective at reducing acid secretion and associated with their own set of adverse events, maybe a reasonable substitute for PPIs in certain patients, such as those with gastroesophageal reflux disease.
While PPIs certainly reduce acid secretion and symptoms in patients with gastroesophageal reflux disease, this drug class may not be appropriate for most patients with this condition.
Many patients can be successfully treated with lifestyle and diet modification.
Mild gastroesophageal reflux disease may be treated with antacids or histamine two (H2) receptor blockers such as ranitidine. If PPI drugs are required, it is usually best to treat patients for brief duration and reevaluate symptoms before moving to chronic PPI use.
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Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. Jul 2012;5(4):219-232. doi:10.1177/1756283x12437358
Thomson AB, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. May 21 2010;16(19):2323-2330.
Chubineh S, Birk J. Proton pump inhibitors: the good, the bad, and the unwanted. South Med J. Nov 2012;105(11):613-618. doi:10.1097/SMJ.0b013e31826efbea
Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ : British Medical Journal. 2008;336(7634):2-3. doi:10.1136/bmj.39406.449456.BE
Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837. doi:10.1371/journal.pone.0058837
Fallahzadeh MK, Borhani Haghighi A, Namazi MR. Proton pump inhibitors: predisposers to Alzheimer disease? J Clin Pharm Ther. Apr 2010;35(2):125-126. doi:10.1111/j.1365-2710.2009.01100.x
Hamzat H, Sun H, Ford JC, Macleod J, Soiza RL, Mangoni AA. Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs Aging. Aug 1 2012;29(8):681-690. doi:10.2165/11632700-000000000-00000
Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurology. 2016. doi:10.1001/jamaneurol.2015.4791
Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. Aug 2015;265(5):419-428. doi:10.1007/s00406-014-0554-0
Kuller LH. Do proton pump inhibitors increase the risk of dementia? JAMA Neurology. 2016. doi:10.1001/jamaneurol.2015.4931
Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. Dec 11 2013;310(22):2435-2442. doi:10.1001/jama.2013.280490
Vitamin B12 and cognitive function: an evidence-based analysis. Ont Health Technol Assess Ser. 2013;13(23):1-45.
Ness-Jensen E, Hveem K, El-Serag H, Lagergren J. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol. Feb 2016;14(2):175-182 e173. doi:10.1016/j.cgh.2015.04.176
Sontag SJ. The medical management of reflux esophagitis. Role of antacids and acid inhibition. Gastroenterol Clin North Am. Sep 1990;19(3):683-712.
Sabesin SM, Berlin RG, Humphries TJ, Bradstreet DC, Walton-Bowen KL, Zaidi S. Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group. Arch Intern Med. Dec 1991;151(12):2394-2400.
Pace F, Pace M. The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. Aug 2010;4(4):423-427. doi:10.1586/egh.10.38