By: Amanda Kastel PharmD Candidate c\/o 2027 <\/p>\n\n\n\n
Sleep aid medications are widely used throughout the United States and have long been viewed as a \u201cquick fix\u201d to treat insomnia. In a survey conducted by the American Academy of Sleep Medicine, out of 2,010 adults in the United States, 20% reported using over-the-counter (OTC) medications to help them sleep.1<\/sup> According to another report, the global OTC sleep aid market was valued at $20.1 billion in 2025.2<\/sup> These numbers are alarming, given that the most popular over the counter sleep aids are first-generation antihistamines with an undesirable side effect profile, especially when used chronically or by the geriatric population. <\/p>\n\n\n\n Diphenhydramine and doxylamine are 2 of the most popular OTC sleep aid medications. Not only are they available as stand-alone products (ZzzQuil, Benadryl, Unisom), but they are also frequently used in combination with other medications, available as products such as Tylenol PM, Advil PM, and NyQuil. Many of these medications have become household names because they are readily available, relatively inexpensive, and are effective at inducing and maintaining sleep. <\/p>\n\n\n\n Mechanism of Action & Side Effects<\/strong> <\/p>\n\n\n\n Diphenhydramine and doxylamine share the same mechanism of action in inducing sleep and only vary slightly in their pharmacokinetic properties. They are both first-generation antihistamines and are lipophilic enough to cross the blood-brain barrier. They are non-selective in receptor binding, as they have affinity for not only central and peripheral H1 receptors, but also act as antagonists at muscarinic receptors. Within the CNS, they act as inverse agonists at the H1 receptor, thereby resulting in drowsiness and justifying their use as sleep aids. Their undesirable anticholinergic side effect profile results from the blockade of acetylcholine from binding to muscarinic receptors.3 <\/sup>Anticholinergic side effects include dry mouth, urinary retention, constipation, tachycardia, reduced saliva and tear production, and worsening of dementia and confusion, particularly in older adults.4<\/sup> <\/p>\n\n\n\n Clinical Implications<\/strong> <\/p>\n\n\n\n The Beers Criteria is a well-renowned set of evidence-based guidelines for potentially inappropriate medications to avoid in older adults (>65) and is intended for use by healthcare professionals. First-generation antihistamines, whether as a single agent or part of a combination product, are listed in the Beer\u2019s Criteria with a strong<\/em> recommendation to avoid <\/em>use in older adults. This is justified because older patients not only have reduced clearance of these medications, but they also have a more permeable blood-brain barrier, making them more susceptible to the harmful anticholinergic effects such as confusion, falls, and worsening dementia. <\/p>\n\n\n\n Alarming Emerging Research<\/strong> <\/p>\n\n\n\n In 2015, a prospective cohort study 5 <\/sup>was published in JAMA, assessing the cumulative use of anticholinergics in patients 65 years and older. The primary objective was to examine the association between 10-year cumulative anticholinergic use and the risk for dementia. Though this study examined all anticholinergics and not just doxylamine and diphenhydramine, nearly 70% of the 3,434 patients studied were taking at least one first-generation antihistamine, further amplifying the concern of inappropriate use of OTC sleep aids. This study was well-designed and showed a dose-response correlation to assess the primary objective. <\/p>\n\n\n\n Participants in the highest exposure category (Total standardized daily dose >1095) had a statistically significant increased risk for dementia (adjusted HR, 1.54 [95% CI, 1.21-1.96]) and Alzheimer\u2019s Disease (adjusted HR, 1.63 [95% CI, 1.24-2.14]) compared with those with no use. <\/p>\n\n\n\n Several other studies show a statistically significant association between increased anticholinergic use and increased risk of dementia.6,7 <\/sup>However, it is important to note that since none of these studies are randomized controlled trials, they cannot prove causationand can only suggest a correlation. Still, healthcare professionals should carefully consider these findings when treating patients, as the mechanism is biologically plausible and safer alternatives are available for insomnia.<\/p>\n\n\n\n The Role of the Pharmacist<\/strong> <\/p>\n\n\n\n In 2023, a study was conducted in which clinical pharmacists assessed and managed fall risk in geriatric patients taking at least one anticholinergic medication. The study found that risk of falls increased 2.5-fold in patients with high anticholinergic burden (OR (95% CI)\u2009=\u20092.503 (1.071\u20135.852); p<\/em>\u2009=\u20090.034). Anticholinergic burden was significantly reduced as a result of interventions by the clinical pharmacist (p<\/em>\u2009=\u20090.010).8<\/sup> <\/p>\n\n\n\n In their 2024 publication of APhA OTC, the American Pharmacist\u2019s Association strongly urged pharmacists to emphasize sleep hygiene to patients struggling with insomnia. Patients should be counseled to limit daytime naps to 20-30 minutes, avoid excess fluids before bedtime, avoid electronics at least 1-2 hours before bedtime, establish a regular sleep pattern, and ensure their bedroom is comfortable and only used for sleeping.9<\/sup> <\/p>\n\n\n\n APhA also recommends that patients older than 65 should not self-treat their insomnia and must be referred to a physician. All patients should be advised that the risks of diphenhydramine and doxylamine may outweigh the benefits. All patients with chronic insomnia that does not resolve with proper sleep hygiene should be referred to a physician, as there may be an underlying cause that needs to be addressed. <\/p>\n\n\n\n Conclusion<\/strong> <\/p>\n\n\n\n The widespread use of potentially harmful OTC sleep aids highlights the pivotal role of the pharmacist in patient education. First-generation antihistamines have many undesirable anticholinergic side effects, and new evidence associates chronic use with increased risk of dementia. Whether in the inpatient or community setting, pharmacists are uniquely positioned as the most accessible healthcare providers to educate patients on these risks, discourage inappropriate use, and emphasize safer alternatives for managing insomnia. <\/p>\n\n\n\n REFERENCES<\/p>\n\n\n\n By: Amanda Kastel PharmD Candidate c\/o 2027 Sleep aid medications are widely used throughout the United States and have long been viewed as a \u201cquick fix\u201d to treat insomnia. In a survey conducted by the American Academy of Sleep Medicine, out of 2,010 adults in the United States, 20% reported using over-the-counter (OTC) medications to…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-4161","post","type-post","status-publish","format-standard","hentry","category-clinical"],"views":158,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4161","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=4161"}],"version-history":[{"count":1,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4161\/revisions"}],"predecessor-version":[{"id":4162,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/4161\/revisions\/4162"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=4161"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=4161"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=4161"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}\n