Evidence-Based Reviews

Sedative-hypnotics for sleepless geriatric patients

Current Psychiatry. 2014 October;13(10):36-39, 46-50, 52

Age-related physiologic changes, risk of adverse effects guide your prescribing

References

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Mr. R, 75, is having difficulty sleeping. When he goes to bed, he lies there for what seems like forever, unable to fall asleep. He feels “so tired” and ends up taking naps during the day, but he cannot break this cycle. He has tried using over-the-counter products with little relief.

Mr. R’s primary care physician prescribes zaleplon, 10 mg/d, and asks him to call the clinic in 2 weeks to discuss his progress. He takes zaleplon as directed for several nights and begins to feel “sluggish” during the day, both mentally and physically, despite reporting an increase in the overall amount of sleep at night.

Sedative-hypnotic drugs are among the most commonly used medications in the United States. Use of these drugs, as well as anxiolytics, has increased from 2.8% between 1988 and 1994 to 4.7% between 2007 and 2010, according to the Department of Health and Human Services.¹ In 2011, drugs categorized as sedative-hypnotics or antipsychotics were involved in 6.1% of all human exposures identified in the American Association of Poison Control Centers’ National Poison Data System.² Therefore, an understanding of clinical and pharmacological variables related to safe and effective use is important for clinicians prescribing and monitoring therapy with these agents.

Neuropsychiatric disorders are prevalent among geriatric patients and are associated with age-related physiologic changes in the CNS.³ Such changes involve:
• neuroanatomy (brain atrophy, decreased neuronal density, increased plaque formation)
• neurotransmitters (reduced cholinergic transmission, decreased synthesis of dopamine and catecholamines), and
• neurophysiology (reduced cerebral blood flow).

These physiologic processes manifest as alterations in mental status, reflexes, sensation, gait, balance, and sleep. Examples of sleep changes among geriatric patients include decreased sleep efficiency, more frequent awakenings, and more variable sleep duration.^3,4 Sleep disorders also may be related to mental disorders and other medical conditions.⁵ For example, the prevalence of sleep-related respiratory disorders, such as obstructive sleep apnea and central sleep apnea, increases with age.⁶

Sleep disorders are common among geriatric patients. In a large epidemiologic study of sleep complaints in patients age ≥65, more than one-half of patients had at least 1 sleep complaint (ie, difficulty falling asleep, trouble waking up, early awakening, need for naps, and feeling ill-rested).⁷ As many as 34% of patients reported symptoms of insomnia. In an analysis of National Ambulatory Medical Survey Data over 6 years, 24.8% to 27.9% of sleep-related medical office visits were attributed to patients age ≥65.⁸

Pharmacology in aging
Prescribing sedative-hypnotic drugs is not routinely recommended for older patients with a sleep disorder. Geriatric patients, compared with younger patients, are at higher risk of iatrogenic complications because of polypharmacy, comorbidities, relative renal and hepatic insufficiency, and other physiologic changes leading to alterations in drug exposure and metabolism (Table 1).^9-12

Aging is associated with changes in body composition, including an increase in total body fat and decrease in lean body mass and total body water. These changes, as well as a prolonged GI transit time, decrease in active gut transporters, decreased blood perfusion, and decrease in plasma proteins such as albumin (because of reduced liver function or malnutrition), may lead to alteration in drug absorption patterns and may increase the volume of distribution for lipophilic drugs. Additionally, the elimination half-life of some drugs may increase with age because of larger volumes of distribution and reduction in hepatic or renal clearance.

The clinical significance of these changes is not well established. Although the process of drug absorption can change with age, the amount of drug absorbed might not be significantly affected. An increase in the volume of distribution and reduction in drug metabolism and clearance might lead to increasing amounts of circulating drug and duration of drug exposure, putting geriatric patients at an increased risk for adverse effects and drug toxicity.⁹

Among these mechanisms, Dolder et al¹¹ hypothesized that drug metabolism catalyzed by cytochrome P450 (CYP) enzymes and renal excretion may be of greatest concern. Although in vitro studies suggest that concentration of CYP enzymes does not decline with age, in vivo studies have demonstrated reduced CYP activity in geriatric patients.^11,12 Theoretically, a reduction in CYP activity would increase the bioavailability of drugs, especially those that are subject to extensive first-pass (ie, hepatic) metabolism, and may lead to a reduction in systemic clearance.

Independent of metabolic changes, geriatric patients are at risk of reduced renal clearance because of age-related changes in glomerular filtration rate. Pharmacodynamic changes might be observed in older patients and could be a concern even in the setting of unaltered pharmacokinetic factors.9 These changes usually require administering smaller drug dosages.

Sedative-hypnotics for sleepless geriatric patients

References

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