Sedative-hypnotics for sleepless geriatric patients

Clinical practice guidelines
Non-pharmacotherapeutic interventions, such as behavioral (eg, sleep hygiene mea­sures) and psychological therapy, are rec­ommended for initial management of sleep disorders in geriatric patients.^13,33 In con­junction, the American Medical Directors Association (AMDA) recommends address­ ing underlying causes and exacerbating fac­tors (eg, medical condition or medication).³³ The AMDA recommends avoiding long-term pharmacotherapy and advises caution with BZD-hypnotic drugs, tricyclic antide­pressants, and antihistamines. The American Academy of Sleep Medicine (AASM) recom­mends an initial treatment period of 2 to 4 weeks, followed by re-evaluation of con­tinued need for treatment.¹³ The AASM recommends short- or intermediate-acting BzRAs or ramelteon for initial pharmaco­logic management of primary insomnias and insomnias comorbid with other condi­tions. The AASM also recommends specific dosages of BzRAs and BZDs for geriatric patients, which coincide with manufacturer-recommended dosages (Table 2).^14-29

Barbiturates, chloral hydrate, and non-barbiturate, non-BZD drugs such as mep­robamate are not recommended because of potential significant adverse effects and tolerance/dependence, and low therapeu­tic index. The AASM advises caution when using prescription drugs off-label for insom­nia (eg, antidepressants, antiepileptics, antipsychotics) and recommends avoiding them, if possible, because of limited evi­dence supporting their use.¹³

Safety concerns
Two commonly used references contain rec­ommendations for sedative-hypnotic medi­cation use in geriatric patients.^30,34 According to Gallagher et al’s³⁴ Screening Tool of Older Person’s Prescriptions (STOPP), long-term (>1 month) use of long-acting BZDs (eg, flurazepam, diazepam) and prolonged use (>1 week) of first-generation antihistamines (eg, diphenhydramine, doxylamine) should be avoided in patients age ≥65 because of the risk of sedation, confusion, and anti­cholinergic side effects. STOPP recognizes that any use of BZDs, neuroleptics, or first-generation antihistamines may contrib­ute to postural imbalance; therefore these agents are not recommended in older patients at risk for falls.

In the 2012 American Geriatrics Society (AGS) Beers Criteria, the AGS recommends avoiding barbiturates in older adults because of the high rate of physical depen­dence, tolerance to sleep effects, and over­dose risk at low dosages.³⁰ The AGS also recommends avoiding BZDs, stating that older adults have increased sensitivity to these agents and are at an increased risk of cognitive impairment, delirium, falls, frac­tures, and motor vehicle accidents when taking these drugs. Non-BZD BzRAs also should not be prescribed to patients with a history of falls or fractures, unless safer alternatives are not available.

The FDA has issued several advisory reports regarding sedative-hypnotic drugs. In 2007, all manufacturers of sedative-hypnotic drugs were required to modify their product labeling to include stronger language about potential risks.35 Among these changes, warnings for ana­phylaxis and complex sleep-related behav­iors were added. Also, the FDA requested that manufacturers of sedative-hypnotic drugs develop and provide patient medi­cation guides, advising consumers on the potential risks and precautions associated with these drugs. More recently, the FDA announced changes to dosing recommen­dations for zolpidem-containing products because of the risk of impaired mental alertness36; manufacturers were required to lower the recommended dosages for each product.

Manufacturers of FDA-approved sedative-hypnotic drugs urge caution when prescribing these medications for geriatric patients, citing the potential for increased sensitivity, manifesting as marked excite­ment, depression, or confusion (eg, barbi­turates), and greater risk for dosage-related adverse effects (eg, oversedation, dizziness, confusion, impaired psychomotor perfor­mance, ataxia).^17-29

Use in clinical practice
Several variables should be considered when evaluating appropriateness of phar­macotherapy, including characteristics of the drug and the patient. Geriatric patients may be prone to comorbidities resulting from age-related physiologic changes. These diseases may be confounding (ie, contributing to sleep disorders); examples include medical illnesses, such as hyperthyroidism and arthritis, and psychiatric illnesses, such as depression and anxiety.³⁷ Other conditions, such as renal and hepatic dysfunction, may lead to alteration in drug exposure. These condi­tions should be assessed through routine renal function tests (eg, serum creatinine and glomerular filtration rate) and liver function tests (eg, serum albumin and liver transaminases).

Multiple comorbidities suggest a higher likelihood of polypharmacy, leading to other drug-related issues (eg, drug-drug interactions). Although these issues may guide therapy by restricting medication options, their potential contribution to the underlying sleep complaints should be con­sidered.³⁷ Several drugs commonly used by geriatric patients may affect wakefulness (eg, analgesics, antidepressants, and anti­hypertensives [sedating], and thyroid hor­mones, corticosteroids, and CNS stimulants [alerting]).

CASE CONTINUED
In Mr. R’s case, zaleplon was initiated at 10 mg/d. Because of his age and the nature of his sleep disorder, the choice of sedative-hypnotic was suitable; however, the prescribed dosage was inappropriate. The sluggishness Mr. R experienced likely was a manifestation of increased exposure to the drug. According to manufacturer and AASM recommendations, a more appropriate dosage is 5 mg/d.^13,23 Mr. R’s medical history and current medica­tions, and his hepatic and renal function, should be assessed. If Mr. R continues to have issues with sleep initiation, zaleplon, 5 mg at bedtime, should be considered.