Episode 221: Insomnia Pharmacotherapy in Adults

ARREAZA: Today we will expand on other treatments for insomnia in adults. MOIRA: Yes, we spent some time explaining the assessment of insomnia and the first-line treatment, Cognitive Behavioral Therapy for Insomnia (CBT-I). We also mentioned sleep hygiene. You can listen to episode 220 if you want to learn more about that. Medication should be considered a secondary option. The American College of Physicians (ACP) recommends that clinicians use a shared decision-making approach, including a discussion of the benefits, harms, and costs of short-term use of medications, to decide whether to add medication in adults with chronic insomnia disorder in whom CBT-I alone was unsuccessful.  In general, pharmacotherapy is associated with risks of dependence, tolerance, and poorer quality sleep, whereas evidence-based psychotherapies, like CBT-I, result in better long-term outcomes, no drug dependence or polypharmacy risk, and potential cost savings. ARREAZA: Yes, we will start this episode by talking about medications. If you practice primary care, I’m 100% sure that a patient has asked you for “sleeping pills” in clinic. Moira, I know our listeners want to hear about meds. What can you tell about meds to treat insomnia? Moira:We can really split pharmacotherapy for sleep into two categories, OTC, and prescription. And many folks reach for OTC sleep aids before talking to a clinician. When we say OTC sleep aids, we’re mostly talking about sedating antihistamines, like diphenhydramine and doxylamine, which are common in products marketed for occasional sleep difficulties. Melatonin is often marketed as a supplement rather than a drug, but it’s also widely used OTC in many places, though regulations and quality vary by country. ARREAZA: Exactly. Several studies describe widespread use of these agents among adults and especially older adults, who may face sleep problems related to comorbidities and polypharmacy. Many older adults use OTC sleep aids, often without consulting a healthcare professional or reading labels carefully. Moira: And there’s evidence that a substantial share of OTC sleep products contains diphenhydramine or doxylamine—first-gen antihistamines that carry anticholinergic burden, which is particularly relevant for older adults. Melatonin’s story is similarly mixed for efficacy. It can modestly affect sleep onset and duration in some populations, especially older adults or circadian rhythm–related sleep problems, but the overall clinical impact is small. What about on the prescription side? DR. ARREAZA: “Z-drugs” are nonbenzodiazepine sedative-hypnotics that enhance the effects of GABA (neurotransmitter). For example, Zolpidem, Zaleplon, eszopiclone. The risks of benzodiazepine use are significant.Benzodiazepine use is associated with increased fall risk across all age groups, and older adults are the highest risk group. That’s something we should mention to patients who are requesting a “sleeping pill”, “you may sleep a little better, but you may fall.” A meta-analysis of randomized trials in adults over 60 found that benzodiazepines (vs placebo) caused: 2.6× more psychomotor problems (like falls and car accidents), 3.8× more daytime sleepiness, 4.8× more cognitive impairment. Also, benzodiazepine use is associated with a 34% increased risk of hip fractures (RR 1.34) in older adults. MOIRA: Very significant. Benzodiazepine use is only recommended for four weeks or less due to unproven long-term efficacy and the risk of tolerance, dependence, and misuse. Psychological and physical dependence on benzodiazepines can develop within a few weeks of regular or repeated use. Long-term use is associated with multiple consequences, including dependence, and even increased risk of opioid use.  Dr ARREAZA: And the withdrawal symptoms are very uncomfortable for benzo dependent patients who try to stop benzos on their own. MOIRA: And with the Z-drugs you were mentioning, the FDA has required that all Z-drugs carry a Boxed Warning highlighting the risk of complex sleep behaviors such as sleepwalking and sleep-driving, which can result in serious injuries including death. Medications such as benzodiazepines and antidepressants should be avoided for the treatment of insomnia in older adults whenever possible. DR ARREAZA: There are other prescription options too. Let’s talk about low-dose doxepin has shown to have one of the best balances between efficacy and tolerability. When I hear “doxepin” the word “old” comes to my mind. And, yes, it was approved in 1969, it is a tricyclic antidepressant used to treat depression, anxiety, and insomnia. The recommended dose for insomnia is between 3-6 mg. It is not free of side effects, but lower doses seem to be better tolerated. Complex behaviors associated with doxepin: Doxepin may cause out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance of doing these activities if you drink alcohol or take other medicines that make you sleepy with this medicine. Reported activities include: "sleep-driving", cooking and eating food, talking on the phone, having sex, or sleepwalking. Moira: Another group of medications is dual orexin receptor antagonists (DORAs) such as lemborexant are considered medications with good balance of efficacy and tolerability. No single medication is considered the "best" for all patients. Let’s remember that optimal medication depends on patient age, comorbidities, safety considerations, and the type of insomnia (sleep onset vs. maintenance.) MOIRA: Older adults deserve special attention. Although insomnia is not a normal part of the aging process, we do see its prevalence increases with age. CBT-I is effective in older adults and is associated with minimal side effects. We can’t talk about sleep meds and older adults without mentioning BEERS criteria, which is a guideline which aims to reduce adverse drug events and polypharmacy by highlighting drugs with risks outweighing benefits, urging safer alternative. In sleep medicine and insomnia management for older adults, Beers Criteria explicitly flag sedating antihistamines (e.g., diphenhydramine, doxylamine) as potentially inappropriate for elderly patients due to anticholinergic burden and adverse effects such as delirium, cognitive impairment, sedation, and falls risk. MOIRA: Yes! So again, I want to highlight that the first line treatment should always be CBT-I, but when this isn't working or isn't an option, then think about adding pharmacotherapy. We should really be sharing that OTC options should only be for occasional sleep trouble, not chronic insomnia. Also, be mindful of age-related risks. And consider melatonin with caveats, melatonin may be an option with generally small sleep-onset effects but again, short-term use and quality matters. To close, OTC sleep aids fill a real need for short-term relief, but they’re not a substitute for diagnosis and evidence-based treatment of insomnia, especially in older adults where safety is a particular concern. And our prescription options like benzos, z drugs, antidepressants, aren’t much better. DR. ARREAZA: Primum non nocere (“first, do no harm”) is a chief consideration in insomnia management. Sleep is foundational to health, and I hope this helps our colleagues feel more confident in addressing it.If you found this helpful, share it with a friend or colleague and rate us wherever you listen to us. This is Dr. Arreaza, signing off. Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!  _____________________ References: Morin, C. M., & Buysse, D. J. (2024). Management of Insomnia. The New England journal of medicine, 391(3), 247–258. https://doi.org/10.1056/NEJMcp2305655 Healy, W. J., Khayat, R. N., & Kwon, Y. (2024). Insomnia: Advancements and Limitations of Current Management Strategies. American family physician, 109(2), 107–108. https://pubmed.ncbi.nlm.nih.gov/38393789/ Drugs.com. (2025, August 6). Doxepin. Retrieved April 15, 2026, from https://www.drugs.com/doxepin.html Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/. Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!