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Pharmacological Considerations for the Treatment of Insomnia in Older Adults

18 Mar 2021 6:07 PM | Anonymous

By: Hannah Michael, PGY1 Pharmacy Resident, University of Missouri Health Care

As adults age, observed changes occur in their sleep patterns, resulting in a higher prevalence of insomnia in the older patient population, or those aged 65 years and older. In normal physiologic sleep processes, sleep is divided into non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. NREM sleep is then further divided into three different stages: N1, N2, and N3. N1 and N2 are categorized into light sleep with N2 accounting for around 48% of sleep time when brain waves begin to slow. N3 sleep is composed of very slow brain waves, also referred to as slow wave sleep.1 As patients age, nightly sleep begins to naturally shorten, however, there are other notable sleep changes that develop in older adults. There tends to be a decrease in total sleep time, a decrease in sleep efficiency, or the ratio of time asleep to time spent in bed, a lower percentage of both slow-wave sleep and REM sleep, and lastly, a decrease in REM latency, which is an important measure in sleep quality as it is the time from sleep onset to the first epoch of REM sleep.2 The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines insomnia as a sleep disturbance that causes significant clinical distress or functional impairment and occurs at least three nights a week for three months.3 The International Classification of Sleep Disorders 3rd Edition goes on to further divide each type into either primary, further categorized into idiopathic, paradoxical, and inadequate sleep hygiene, or secondary, which is attributed to medical conditions and mental disorders.4 Similar to the DSM-5 classification, chronic insomnia disorder includes all subtypes that occur at least three nights a week for at least three months.

Insomnia, if left untreated, may lead to increased rates of depression, cognitive impairment, as well as other medical conditions such as diabetes, cancer, or hypertension.5 Another important factor to keep in mind with this patient population is the disruption in standard time cues that otherwise develop with a consistent and regular schedule. The geriatric population is often retired, so fixed work schedules and mealtimes may change, and this may contribute to the development of insomnia when the homeostatic process that drives the need to sleep or stay awake is not regulated as it was prior to these daily adjustments. Understanding these developmental changes is essential in order to appropriately identify therapy modifications and recommendations for such a commonly encountered sleep disorder.

Prior to the consideration of pharmacological agents, sleep hygiene and other non-pharmacological approaches to treating insomnia should always be implemented. Important factors of sleep hygiene specifically include the incorporation of regular exercise and meals during the day; avoidance of stimulants, large meals, and electronic usage close to bedtime; limiting daytime naps; and optimizing one’s sleep environment, which includes maintaining cooler room temperatures and other physical bed considerations to maximize sleep comfort. Other non-pharmacological approaches include the use of cognitive behavioral therapy for insomnia (CBT-I), which is highlighted by the American Academy of Sleep Medicine (AASM) as a standard of treatment for insomnia.6 CBT-I is centered on identifying incorrect thoughts, beliefs, or knowledge about sleep and behaviors related to sleep. Additional methods include sleep restriction, which, with the help of a sleep diary, aims to make small adjustments each week to build back sleep drive. Lastly, stimulus control is another approach to train the brain to associate bed with sleep only; in doing this, patients are advised to leave their bed and complete a relaxing activity if unable to sleep, only to return to bed when sleepy.1

There are notable challenges when considering incorporating pharmacological agents for older adults when non-pharmacological approaches alone are insufficient. Prolonged use of different pharmacotherapies is associated with tolerance issues, dependence, and other related challenges, such as residual daytime sedation and cognitive impairment, both of which increase the risk for motor incoordination and resultant falls. The American Geriatrics Society 2019 Beers Criteria offers recommendations to reduce exposure to potentially inappropriate medication use in patients 65 years and older. For example, the guideline recommends avoiding benzodiazepines and nonbenzodiazepine hypnotics in older adults due to potential for adverse events, such as delirium, falls, fractures, and motor vehicle accidents.7 In addition, older patients often require dose adjustments due to changes in muscle mass and renal function, as well as increased sensitivity to adverse effects. These patients are also more likely to be taking additional medications for concomitant disease states, which increases their risk for drug interactions. The AASM provides general recommendations for insomnia depending on the different types, including sleep onset insomnia (difficulty initiating sleep), sleep maintenance insomnia (an inability to stay asleep throughout the night), or a combination of both. With these considerations in mind, understanding the available agents and their common adverse effects and pharmacokinetic profiles may guide appropriate therapy selection. A selected list of therapy agents and their specific characteristics are provided in the table below when considering these sleep aids in the geriatric population.6,8,9


Select review articles provide additional guidance for elderly patients and offer recommendations regarding preferred pharmacotherapy for sleep onset insomnia, including ramelteon, which works as a melatonin receptor agonist, short-acting nonbenzodiazepines (i.e., zaleplon or zolpidem), or melatonin.2,9 Caution is advised with melatonin products due to the varying formulations and inconsistent efficacy for each patient.

For sleep maintenance insomnia, beneficial pharmacotherapy agents may include suvorexant, which was approved in 2014 as a first-in-class insomnia drug that antagonizes both orexin type 1 and type 2 receptors, or low-dose doxepin, a tricyclic antidepressant. Of note, antidepressants may have more value in older patients with comorbid depression.

Lastly, for sleep maintenance or sleep onset insomnia, non-benzodiazepines, which agonize the benzodiazepine receptors at varying GABA subunits, may be useful with careful consideration of the pharmacokinetic properties. For example, eszopiclone may offer additional benefit for sleep maintenance insomnia due to its longer half-life. Each of these agents is advised to be prescribed for short-term use only, and benzodiazepines are generally suggested to be avoided in the elderly due to increased likelihood of falls, cognitive disruption, dependence, and difficulty with discontinuation.

Sleep status and quality of sleep remain important concerning the older population, as a natural decline in normal physiologic sleep processes is likely to be observed in these patients. Recognizing the challenges that are associated with drug therapy for the treatment of insomnia in the elderly is essential when deciding to incorporate pharmacological agents. Older patients are more likely to be on interacting drug therapies and may require dose adjustments when considering declines in renal function and increased sensitivity to the available treatments. Most importantly, non-pharmacological approaches should always be at the forefront of therapy and be incorporated into each patient-specific plan, as the development and continuation of improved sleep habits benefits all types of insomnia no matter a patient’s age.

References:

  1. Patel D, Steinberg J, Patel P. Insomnia in the elderly: a review. J Clin Sleep Med. 2018;14(6):1017-1024.
  2. Suzuki K, Miyamoto M, Hirata K. Sleep disorders in the elderly: diagnosis and management. J Gen Fam Med 2017;18:61-71
  3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Fifth edition. 2013.
  4. American Academy of Sleep Medicine. International classification of sleep disorders, 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
  5. The Epidemiology of Insomnia in Older Adults and Current Treatment Landscape. The American Journal of Managed Care; 2019.
  6. Sateia M, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an american academy of sleep medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349.
  7. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67:674-694.
  8. Temazepam, Triazolam, Eszopiclone, Zolpidem, Zaleplon, Ramelteon, Doxepin, Trazodone, Suvorexant, Diphenhydramine, Doxylamine, Melatonin, Valerian. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed February 10, 2021.
  9. Abad VC, Guilleminault C. Insomnia in elderly patients: recommendations for pharmacological management. Drugs & Aging. 2018;35(9):791-817

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