When starting a new prescription drug (or even an over-the-counter medication), how many of us don’t bother to discuss potential side effects with our health care provider or take the time to read the patient insert?
For some drugs—and some people—such a “no brainer” could actually be risky. Here is a quick look at research that is emerging about some popular classes of medications that raise questions we may want to discuss with our doctors.
Can Anticholinergics Increase Your Risk of Dementia?
Readers may remember some controversy in the press several years ago about whether a class of drugs known as anticholinergics can increase risk for dementia. Anticholinergics (ACs) block the action of a chemical messenger known as acetylcholine that transfers signals between cells, stimulating muscle contractions. They include some first-generation antihistamines, medications used for overactive bladder/urinary incontinence, tricyclic antidepressants, and some drugs used to relieve Parkinson’s symptoms.1, 2
A team from the University of Washington published a paper in 2015 in JAMA Internal Medicine documenting their study of 3,434 randomly selected adults 65 and older with no dementia and followed them for approximately seven years. Using data that included computerized pharmacy dispensing records and periodic cognitive assessments, the research team was able to document almost 800 participants who developed dementia and found that study subjects who used AC drugs were more likely to develop dementia than subjects who did not. Their paper concluded, “Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time. 3
Several more recent studies have found results that reinforce concerns about AC medications. A team of researchers from Indiana University, the Mayo Clinic, University of California Berkeley, University of Southern California, and the University of California San Francisco assessed whether there was an association between anticholinergic medication use and cognition, glucose metabolism, and brain atrophy. They published findings in 2016 concluding, “The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should be discouraged if alternative therapies are available.”4
A group of researchers in Taiwan followed patients aged 50 and older who were newly diagnosed with lower urinary tract symptoms (LUTS) from January 2001 until the end of the research project in 2012. The patients were divided into several groups depending upon the amount of their cumulative daily doses of AC meds. Their paper concluded, “Our study indicates that higher cumulative anticholinergic exposure is associated with an increase in the risk of incident dementia in patients with LUTS aged 50 years of age and over. Either using one anticholinergic agent or switching anticholinergic agents cumulatively increases this risk. Therapeutic risks and benefits of using anticholinergics in LUTS treatment should be clinically reviewed and weighed.”5
Some of the more commonly prescribed ACs include atropine (Atropen), benztropine mesylate (Cogentin), and darifenacin (Enablex). A longer list is available here.1 Here is a quick read from Reuters that does a nice job of explaining the potential risk of cognitive decline with use of AC medications. 6
The video below from USA Today recaps some of their article sharing results from “a study out of the University of Nottingham in the United Kingdom [that] found there is a link between dementia and certain classes of anticholinergic drugs. The drugs — particularly antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs — resulted in nearly ‘50% increased odds of dementia,’ according to the observational study published… in the peer-reviewed JAMA Internal Medicine journal.” 7
A study showed commonly prescribed medications may be linked to a higher chance of dementia. USA TODAY
Can Statins Make You Anxious or Angry?
Anyone who takes statins to lower cholesterol and protect against heart attack or stroke has probably felt like a ping-pong ball bouncing between good news and bad news about the drug. The Mayo Clinic website urges users to weigh the risks and benefits and speak with their health care providers if they feel they are experiencing common complaints linked to the drugs such as “muscle pain, digestive problems and mental fuzziness.”8
While statins are usually discussed as a general group, there are actually several different formulations and brand names including “atorvastatin (Lipitor), fluvastatin (Lescol XL), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor, Ezallor) and simvastatin (Zocor, FloLipid).”8
Dr. Beatrice Golomb and her team at the University of California, San Diego (UCSD) have been looking more closely into a potential relationship between statin use and aggression that had been reported in previous studies by other research groups. Dr. Golomb’s team used a double-blind, randomized, placebo-controlled study of 692 men and 324 postmenopausal women. Baseline aggression was evaluated, and study participants were each followed for a duration of 6 months. The team found “statins generally decreased aggression in men; and generally increased aggression in women.” 9
In perhaps the most extreme example of behavior change in a study participant, in reporting adverse events during the study, the Golomb paper shared this, “A woman dropped from the study at her husband’s urging at ~1 month into participation due to a reported marked adverse behavioral change. When unblinding was later undertaken, it was determined she had been on pravastatin. This participant communicated with us several years later, due to legal action emanating from the adverse behavioral change during her participation in the study—which reportedly led her to be fired from her job.”9
In making heads or tails of these opposite results for men and women, a UCSD press release offered this summary of information in the research paper by Dr. Golomb’s team: “The full set of biological explanations linking statins to behavior remains a work-in-progress. One early hypothesis was that lower levels of cholesterol may reduce brain serotonin. (The connection between low brain serotonin activity and violence has been viewed as one of the most consistent findings in biological psychiatry.) Whole blood serotonin — which can relate inversely to brain serotonin — was not a predictor in this study. However, testosterone and sleep were, for those on simvastatin. Golomb postulates that other factors, such as oxidative stress and cell energy, may play a role.” 10
An article in Psychology Today shares a recollection by Dr. Golomb about a well-respected physician who had not been aware of his own behavioral changes, but was “perceived by others at the hospital as having become inappropriately short-tempered…So he was referred to the hospital psychiatrist, and it was noted that the time course of the change coincided with him being placed on a statin…They stopped the statin, and everyone else recognized that the problem went away, but the physician still didn’t recognize that there had ever been a problem.” 11
The prescribing information from Merck, the maker of a brand of simvastatin called Zocor, lists memory impairment and depression as “additional adverse reactions [that] have been identified during postapproval use of simvastatin.” 12 The prescribing information from Sandoz Canada for their pravastatin tablets lists depression, anxiety, and nervousness as potential side effects and advises people experiencing these effects classified as “uncommon” talk with their doctor or pharmacist only if the symptoms are severe.13
The Psychology Today article recaps some of the medical literature and observes that “cholesterol drugs may trigger mood changes in susceptible individuals.” Noting that more research is needed because the evidence is still limited about whether statins may cause irritability and aggression, the health writer (who has a master’s in health psychology) advises readers to talk to their health care provider if there are concerns and to “keep in mind that it may be easier for others to recognize a change in your behavior than it is to see it in yourself.” 11
Here is an interesting read from the BBC that does a great job of explaining some of these behavioral issues seen with statins and other drugs.14
Bottom Line: In the end, it is up to each of us to understand the risks and benefits of the prescription and over-the-counter drugs we take. It is important to always consult with your health care provider if you are concerned with risks and/or if you are considering stopping the medication.
1Cafasso J. Anticholinergics. Healthline. 9 August 2019. https://www.healthline.com/health/anticholinergics
2Merz B. Common Anticholinergic Drugs Like Benadryl Linked to Increased Dementia Risk. Harvard Health Blog. 28 January 2015. https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667
3Gray SL et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine. 2015 Mar;175(3):4017. https://www.ncbi.nlm.nih.gov/pubmed/25621434
4Risacher SL et al; Alzheimer’s Disease Neuroimaging Initiative. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurology. 2016 Jun 1;73(6):721-32. https://www.ncbi.nlm.nih.gov/pubmed/27088965
5Wang YC et al. Cumulative use of therapeutic bladder anticholinergics and the risk of dementia in patients with lower urinary tract symptoms: a nationwide 12-year cohort study. BMC Geriatrics. 2019 Dec 30;19(1):380. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937838/
6Rapaport L. Common Medicines Tied to Changes in the Brain. Reuters Health News. 20 April 2016. https://www.reuters.com/article/us-health-brain-otc-drugs/common-medicines-tied-to-changes-in-the-brain-idUSKCN0XH1Y8
7Aspegren E. These Commonly Prescribed medications May Increase Your Risk of Dementia, Study Finds. USA Today. 25 June 2019. https://www.usatoday.com/story/news/health/2019/06/24/common-prescriptions-may-increase-risk-dementia-study/1551165001/
8Mayo Clinic Staff. Statin Side Effects: Weigh the Benefits and Risks. 14 January 2020. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20046013
9Golomb BA et al. Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial. PLOS One 2015;10(7):e0124451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488854/
10Science Daily. Statins Linked to Lower Aggression in Men, but Higher in Women. University of California, San Diego Health Sciences. 1 July 2015. https://www.sciencedaily.com/releases/2015/07/150701140851.htm
11Andrews LW. Do Statin Medications Affect Irritability and Aggression? 30 November 2016. Psychology Today. https://www.psychologytoday.com/us/blog/minding-the-body/201611/do-statin-medications-affect-irritability-and-aggression
12Merck & Co. Highlights of Prescribing Information. Zocor (simvastatin) Tablets. Revised March 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019766s078lbl.pdf
13Sandoz Canada. Product Monograph Including Patient Medication Information. Sandoz Pravastatin Tablets. Revised 25 September 2017. p. 43. https://www.sandoz.ca/sites/www.sandoz.ca/files/Pravastatin%20Tablets%20Product%20Monograph.pdf
14Gorvett Z. The Medications That Change Who We Are. BBC Future. 8 January 2020. https://www.bbc.com/future/article/20200108-the-medications-that-change-who-we-are?fbclid=IwAR2i72Fg_fNGu0uSNwOES6QhxaD7U4BXCwgtSU5F0JdHXy3eyjqlmCJmxAs
Video. Dementia Linked to Commonly Prescribed Medicine, Study Says. USA Today. 25 June 2019. https://www.usatoday.com/videos/news/health/2019/06/25/dementia-linked-commonly-prescribed-medicine-study-says/1557426001/
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