Geriatric patients: choose wisely: age-related physiologic changes, risk of adverse effects guide your prescribing.
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 [greater than or equal to]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 [greater than or equal to]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 'educed 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 dearance 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 all (11) 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.' These changes usually require administering smaller drug dosages.
Sedative-hypnotic agents include several barbiturates, benzodiazepines (BZDs), non-BZD benzodiazepine-receptor agonists (BzRAs), a melatonin-receptor agonist (ie, ramelteon), and an orexin-receptor antagonist (ie, suvorexant). (13), (14) Table 2 (page 46) (14-29) summarizes selected sedative-hypnotic drugs. Additional drug classes used to treat insomnia include:
* sedating antidepressants (trazodone, amitriptyline, doxepin, mirtazapine)
* antiepileptic drugs (gabapentin, tiagabine)
* atypical antipsychotics (quetiapine, olanzapine).
Table 1 Effects of age-associated physiologic changes on pharmacokinetic parameters Physiologic Pharmacokinetic parameters Clinical changes implications [down arrow] Total Absorption May observe slight body fat [down * Unaffected for IV drugs decrease in arrow] Lean body * E[down arrow]tent of absorption; mass [down arrow] absorption may be complete, literature Total body water but [T.sub.max] may be longer, suggests that this [down arrow] Gl [C.sub.max] may be lower rarely is motility [down * Reduced for drugs requiring clinically arrow] Plasma lower pH environment significant protein Hypochlorhydria Distribution May require dosage * Reduced for water-soluble reduction of drugs and drugs bound to hydrophilic drugs muscle May observe * Increased for lipid-soluble prolonged time to drugs elimination of lipophilic drugs Note: reduction in protein binding alone does not usually result in clinically significant change in volume of distribution [down arrow] Metabolism Potential increase Hepatic mass [down * Reduced first-pass in bioavailability arrow] Hepatic metabolism of drugs subject blood flow * Reduced Phase I metabolism to e[down arrow]tensive hepatic metabolism and increased drug exposure [down arrow] Elimination Increased plasma Cardiac output * Reduced renal elimination concentration of [down arrow] * Increased elimination drug or Blood flow to half-life metabolites and kidneys and liver duration of drug [down arrow] action Renal mass [down arrow] Renal or hepatic clearance [C.sub.max]: maximum plasma concentration; [T.sub.max]: time to maximum plasma concentration Source: References 9-12
FDA-approved agents for treating insomnia include amobarbital, butabarbital, pentobarbital, phenobarbital, secobarbital, chloral hydrate, diphenhydramine, doxylamine, doxepin, estazolam, flurazepam, lorazepam, quazepam, temazepam, triazolam, eszopidone, zaleplon, zolpidem, ramelteon, and suvorexant. Not all of these drugs are recommended for use in geriatric patients. Barbiturates, for example, should be avoided. (30)
Pharmacokinetic characteristics vary among drugs and drug classes. Choice of pharmacotherapy should account for patient and drug characteristics and the specific sleep complaint. Sleep disorders may be variously characterized as difficulty with sleep initiation, duration, consolidation, or quality. (13) Therefore, onset and duration of effect are important drug-related considerations. Sedative-hypnotic drugs with a short time-to-onset may be ideal for patients with sleep-onset insomnia.
The drugs' duration of effect (eg, presence of active metabolites, long elimination half-life) also must be reviewed. A long elimination half-life may lead to increased drug exposure and unwanted side effects such as residual daytime drowsiness. Despite this, sedative-hypnotic drugs with a longer duration of effect (eg, intermediate- or long-acting drugs) may be best for patients with insomnia defined by difficulty maintaining sleep.
Benzodiazepines vary in their time to onset of effect, rate of elimination, and metabolism. (15-21) BZDs that are FDA-approved for use as sedative-hypnotics are listed in Table 2 (page 46). (14-29) These BLDs have different onsets of effect as evidenced by time to achieve maximum plasma concentration ([T.sub.max]), ranging from 0.5 hours (flurazepam) to 2 hours (estazolam, quazepam, triazolam). The elimination half-life varies widely among these medications, from 1.5 hours (triazolam) to >100 hours (flurazepam). Flurazepam's long half-life is attributable to its active major metabolite. Although most BZDs are metabolized hepatically, temazepam is subject to minimal hepatic metabolism.
Table 2 Characteristics of select oral sedative-hypnotic agents and recommended dosing in geriatric patients Pharmacokinetic characteristics Drug Dosage Absorption Distribution form (onset of (protein effect, binding, Vd) [T.sub.max]) (b) (a) Benzodiazepines Estazolam 1,2 mg [T.sub.max]: High protein tablets 2 hours binding Vd: large Flurazepam 15, 30 mg Onset of High protein (e) capsules effect: 15 to binding Vd: large 20 minutes [T.sub.max]: 0.5 to 1 hour; [T.sub.max] of major metabolite: 10.6 hours Quazepam 15 mg [T.sub.max]: High protein (e) tablets 2 hours binding Vd: large Temazepam 7.5,15, [T.sub.max]: High protein 22.5, 30 mg 1.2 to 1.6 binding Vd: medium capsules hour Triazolam 0.125, 0.25 Onset of High protein mg tablets effect: 0.25 binding Vd: medium to 0.5 hour [T.sub.max]: 2 hours Benzodiazepine-receptor agonists Eszopiclone 1,2,3 mg [T.sub.max]: Moderate tablets 1 hour protein binding Vd: medium Zaleplon 5,10 mg [T.sub.max]: Moderate capsules 1 hour protein binding Vd: medium Zolpidem 5,10 mg Onset of High protein tablets effect: 0.5 binding Vd: small hour [T.sub.max]: 1.6 hour 6.25,12.5 [T.sub.max]: mg ER 1.5 hour tablets 5,10 mg [T.sub.max]: sublingual 0.5 to 3 tablets hour 1.75, 3.5 [T.sub.max]: mg 0.5 to 1.25 sublingual hours tablets 5 mg spray [T.sub.max]: solution 0.9 hour Melatonin-receptor agonist Ramelteon 8 mg Onset of Moderate tablets effect: 0.5 protein hour binding Vd: medium [T.sub.max]: 0.75 hour Orexin-receptor antagonist Suvorexant 5,10,15,20 [T.sub.max]: High protein mg tablets 2 hour binding Vd: small Pharmacokinetic characteristics Drug Metabolism Elimination Recommended (c) (d) adult dosing Estazolam Hepatic; [T.sub.1/2]: Hypnotic: 1 extent high 10 to 24 or 2 mg at Enzyme: CYP hours bedtime 3A4 Geriatric: 0.5 mg initially for small or debilitated patients; 1 mg if healthy Flurazepam Hepatic; [T.sub.1/2]: Hypnotic: 30 (e) extent high 2.3 hours mg at Enzyme: CYP [T.sub.1/2] bedtime 3A4 of major Geriatric: metabolite: 15 mg 47 to 100 hours; mean 126 to 158 hours in geriatric patients Quazepam Hepatic; [T.sub.1/2]: Hypnotic: (e) extent high 39 hours 7.5 mg Enzyme: CYP [T.sub.1/2] initially 3A4 of major Geriatric: metabolite: NS 73 hours Temazepam Hepatic; [T.sub.1/2]: Hypnotic: 15 extent low 3.5 to 18.4 mg at Enzyme: CYP hours, mean bedtime 2B6,2C19,2C9, 8.8 hours Geriatric: 3A4 (all 7.5 mg minor) initially Triazolam Hepatic; [T.sub.1/2]: Hypnotic: extent 1.5 to 5.5 0.25 mg at moderate hours bedtime; Enzyme: CYP 0.125 mg for 3A4 patients with low body weight Geriatric: 0.125 mg initially, 0.25 mg maximum Eszopiclone Hepatic; [T.sub.1/2]: Hypnotic: 2 extent high 6 hours mg at Enzyme: CYP bedtime 3A4, 2E1 Geriatric: 1 mg initially, 2 mg maximum Zaleplon Hepatic; [T.sub.1/2]: Hypnotic: 10 extent high 1 hour mg at Enzyme: CYP bedtime 3A4 Geriatric: 5 mg initially, 10 mg maximum Zolpidem Hepatic; [T.sub.1/2]: Hypnotic: 5 extent high 2.5 to 2.6 or 10 mg at Enzyme: hours bedtime primarily CYP Geriatric: 5 3A4, minor mg 1A2, 2C19, [T.sub.1/2]: Hypnotic: 2C9, and 2D6 2.8 hours 6.25 or 12 mg at bedtime Geriatric: 6.25 mg [T.sub.1/2]: Hypnotic: 5 2.65 to 2.85 or 10 mg at hours bedtime [T.sub.1/2]: 2.5 hours [T.sub.1/2]: Hypnotic: 5 3.0 hours or 10 mg at bedtime Geriatric: 5 mg Ramelteon Hepatic; [T.sub.1/2]: Hypnotic: 8 extent high 1 to 2.6 mg at Enzyme: hours bedtime primarily CYP Geriatric: 1A2, minor 2C NS and 3A4 Suvorexant Hepatic; [T.sub.1/2]: Hypnotic: 10 extent high 12 hours mg at Enzyme: bedtime, 20 primarily CYP mg maximum 3A, minor Geriatric: 2C19 NS (a.) Time to maximum plasma concentration and/or onset of effect specified if available (b.) Extent of protein binding: high: >90%; moderate: <90% and >50%; low: <50%; Vd specified if available: large: >2 L/kg; medium: [less than or equal to]2 and 21 L/kg; small: <1 L/kg (c.) Extent of metabolism: high: <10% excreted unchanged; moderate: [less than or equal to]50% and >10% excreted unchanged; low: >50% excreted unchanged (d.) For half-lives reported as a range, a mean is specified if available (e.) Flurazepam and quazepam are not recommended in geriatric patients because of safety concerns CR: controlled-release; CYP: cytochrome P450; ER: extended-release; NS: not specified; [T.sub.1/2]: elimination half-life; [T.sub.max]: maximum plasma concentration; Vd: volume of distribution Source: References 14-29
There is substantial variation in the pharmacokinetic characteristics of BzRAs. (15), (16), (22-28) There also are differences among the zapi-dem dosage forms; sublingual formulations have the shortest onset of effect. Eszopiclone and zaleplon have low protein binding compared with zolpidem. Elimination half-lives vary among drugs with the shortest attributed to zaleplon (1 hour) and longest to eszopidone (6 hours). All BzRAs are subject to extensive hepatic metabolism.
Ramelteon. Singular in its class, ramelteon is a treatment option for insomnia. (29) This drug has a short onset of effect, moderate protein binding, and extensive hepatic metabolism. Ramelteon is primarily excreted in the urine as its metabolites, and the drug half-life is relatively short.
Suvorexant is the latest addition to the sedative-hypnotic armamentarium, approved by the FDA in August 2014 for difficulty with sleep onset and/or sleep maintenance. (14) As an mexin-receptor antagonist, suvorexant represents a novel pharmacologic dass. Suvorexant exhibits moderately rapid absorption with time to peak concentration ranging from 30 minutes to 6 hours in fasting conditions; absorption is delayed when taken with or soon after a meal. The drug is highly protein bound and extensively metabolized, primarily through CYP3A. The manufacturer recommends dose reduction (5 mg at bedtime) in patients taking moderate CYP3A inhibitors and avoiding suvorexant in patients taking strong CYP3A inhibitors. Suvorexant is primarily excreted through feces and the mean half-life is relatively long.
Considering these characteristics and age-related physiologic changes, the practitioner should be concerned about drugs that undergo extensive hepatic metabolism. Age-related reductions in CYP activity may lead to an increase in drug bioavailability and a decrease in the systemic clearance, (11) which might be associated with an increase in elimination half-life and duration of action. Dosage adjustments are recommended for several BLDs (lower initial and maximum dosages for most agents) and BzIZAs. (17-28) No dosage adjustments for ramelteon or suvorexant in geriatric patients have been specified (14), (29); the manufacturers for both products assert that no differences in safety and efficacy have been observed between older and younger adult patients.
Alternative and complementary medications
Several non-prescription products, including over-the-counter drugs (eg, diphenhydramine, doxylamine) and herbal therapies (eg, melatonin, valerian), are used for their sedative-hypnotic properties. There is a lack of evidence supporting using diphenhydramine in patients with chronic insomnia, and tolerance to its hypnotic effect has been reported with repeated use. (31) Concerns about anticholinergic toxicity and CNS depression limit its use in geriatric patients. Among herbal therapies, melatonin may have the strongest evidence for its ability to alleviate sleep disorders in geriatric patients (32); however, meta-analyses have demonstrated small effects of melatonin on sleep latency and minimal differences in wake time after sleep onset and total sleep time. (13)
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.1133 In conjunction, the American Medical Directors Association (AMDA) recommends addressing underlying causes and exacerbating factors (eg, medical condition or medication). (33) The AMDA recommends avoiding longterm pharmacotherapy and advises caution with BLD-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 ra-melteon for initial pharmacologic management of primary insomnias and insomnias comorbid with other conditions. The AASM also recommends specific dosages of BzRAs and BZUs for geriatric patients, which coincide with manufacturer-recommended dosages (Table 2, page 46). (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)
Two commonly used references contain recommendations for sedative-hypnotic medication use in geriatric patients. (30), (34) According to Gallagher et al's (34) 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 [greater than or equal to]65 because of the risk of sedation, confusion, and anticholinergic side effects. STOPP recognizes that any use of BZUs, 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 a1ertness (36); 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 con-sidered. (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]). 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.
(8.) Morlock RI, Tan M, Mitchell DY. Patient characteristics and patterns of drug use for sleep complaints in the United States: analysis of National Ambulatory Medical Survey Data, 1997-2002. Clin Ther. 2006; 28(7): 1044-1053.
(9.) Diasio RB. Principles of drug therapy. In: Goldman L, Schafer Al, eds. Goldman's Cecil medicine. 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: 124-132.
(10.) Hilrner SN, Ford GA. General principles of pharmacology. In: Halter JB, Ouslander JG, Tmetti ME, et al, eds. Hazzard's geriatric medicine and gerontology 6th ed. New York, NY: McGraw-Hill; 2009: 103-122.
(11.) Dolder C, Nelson M, McKinseyt Use of non-benzodiazepine hypnotics in the elderly: are all agents the same? CNS Drugs. 2007; 21(5): 389-405.
(12.) Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009; 41(2): 67-76.
(13.) Schutte-Rodin 5, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2(X)8; 4(5): 487-504.
(14.) Belsomra [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2014.
(15.) Micromedex Healthcare Series. Greenwood Village, CO: Thomson Efealthc.are. http://micromeciex.com. Accessed August 22,2014.
(16.) Lexicomp. St. Louis, MO: Wolters Kluwer Health. http://www.lexi.com. Accessed August 22,2014. 17. Estazolam [package insert]. Corona, CA: Watson Pharma, Mc; 2008.
(32.) Insomnia. In: Natural Standard. Somerville, MA: Natural Standari https://naturalmedicines.therapeuticreseardtcom/databases/medica-condtions/i/insomnia.aspx. Accessed August 22, 2014.
(33.) American Medical Directors Association. Clinical practice guideline: sleep disorders. Columbia, MD: American Medical Directors Association; 2006.
(34.) Gallagher P, Ryan C, Byrne S. et al. STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. Int J Clin Phannacol Then 2008; 46(2): 72-83.
35. Food and Drug Administration. FDA requests label change for all sleep disorder drug products. http://www.fda.gov/newsevents/newsroom/pressannouncements/2007/ucrn108868.htm. Published Mardi 14, 2007. Accessed August 22,2014.
(36.) Food and Drug Administration. FDA drug safety communication: risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). http://www.fda.gov/drugs/drugsafety/ucm334033.htm. Published January 10, 2013. Accessed August 22, 2014.
37. Cohen-Zion M, Ancoli-Israel S. Sleep disorders. In: Hazzard's geriatric medicine and gerontology 6th ed. New York, NY: McGraw-Hill; 2009: 671-682.
Although the process of drug absorption can change with age, the amount of drug absorbed might not be significantly affected
Prescribing sedative-hypnotic drugs is not routinely recommended for older patients with a sleep disorder
Geriatric patients are at risk of reduced renal clearance because of age-related changes in glomerular filtration rate
Sedative-hypnotic drugs with a longer duration of effect may be best for patients who have difficulty maintaining sleep
No dosage adjustments for ramelteon or suvorexant in geriatric patients have been specified
Non-drug interventions are recommended for initial management of sleep disorders in geriatric patients
Recently, FDA changed dosing recommendations for zolpidem-containing products because of the risk of impaired mental alertness
Geriatric patients may be prone to comorbidities resulting from age-related physiologic changes that may be confounding
RELATED ARTICLE: Practice points
* Review the patient's medical history for conditions that may be related to sleep disorders.
* Initiate non-pharmacotherapeutic management, such as sleep hygiene measures.
* If a sleep disorder persists, determine the need for an agent with a short onset of effect or long duration, or both.
* Assess renal and hepatic function.
* Evaluate the metabolic profile for drugs subject to extensive hepatic metabolism and identify those with active metabolites; such drugs may be associated with increased exposure/effect.
* Once an agent is selected, start with a low dosage and monitor for improvement within 2 weeks.
* Use the lowest effective dosage and limit the treatment period, if possible.
* Watch for drug-related adverse effects, such as residual drowsiness and confusion, and address the risk of falls.
* Monitor for changes in drug therapy; recognize and avoid potentially inappropriate medications.
(18.) Flurazepam [package insert]. Eatontown, NJ: West-Ward Pharmaceutical Corp; 2010.
(19.) Doral [package insert]. Las Vegas, NV: Num Pharma, Inc; 2013.
(20.) Restoril [package insert]. Hazelwood, MO: Mallinc.krodt Inc; 2010.
(21.) Halcion [package insert]. New York, NY: Pharmacia & Upjohn Co; 2013. 22. Lunesta [package insert]. Marlborough, MA: Sunovion Pharmaceuticals Inc; 2012.
(23.) Sonata [package insert]. New York, NY: Pfizer Inc; 2013.
(24.) Ambien [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2013.
(25.) Ambien CR [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2013.
(26.) Edluar [package insert].Somerset, N]: Meda Pharmaceuticals mc; 2009.
(27.) Intermezzo [package insert]. Point Richmond, CA: Transcept Pharmaceuticals, Inc; 2011.
(28.) Zolpirnist [package insert]. Richmond, VA: ECR Pharmaceuticals; 2013.
(29.) Rozerem [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2010.
(30.) The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. j Am Geriatr Soc. 2012; 60(4): 616-631.
(31.) Kirkwood CK, Melton ST. Insomnia, drowsiness, and fatigue. In: Krinsky DL, Berardi RR, Ferreri SP, et al, eds. Handbook of nonprescription drugs: an interactive approach to self-care. 17th ed. Washington, DC: American Pharmacists Association; 2012: 867-884.
RELATED ARTICLE: Related resources
* Institute for Safe Medication Practices. www.ismp.org.
* Med Watch: The FDA Safety Information and Adverse Event Reporting Program. www.fda.gov/Safety/MedWatch/default.htm.
Drug Brand Names
Amitriptyline * Elavil
Amobarbital * Amytal
Butabarbital * Butisol
Chloral hydrate * Somnote
Diazepam * Valium
Diphenhydramine * Benadryl, others
Doxepin * Silenor
Doxylamine * Unisom, others
Estazolam * ProSom
Eszopiclone * Lunesta
Flurazepam * Dalmane
Gabapentin * Neurontin, Gralise, Horizant
Lorazepam * Ativan
Meprobamate * Equanil
Mirtazapine * Remeron
Olanzapine * Zyprexa
Pentobarbital * Nembutal
Phenobarbital * Luminal
Quazepam * Doral
Quetiapine * Seroquel
Ramelteon * Rozerem
Secobarbital * Seconal
Suvorexant * Belsomra
Temazepam * Restoril
Tiagabine * Gabitril
Trazodone * Desyrel
Triazolam * Halcion
Zaleplon * Sonata
Zolpidem * Ambien, Edluar, Intermezzo, Zolpimist
Vicki L. Ellingrod, PharmD, FCCP, is the series editor of Savvy Psychopharmacology.
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(3.) Inouye SK. Neuropsychiatric aspects of aging. In: Goldman L, Schafer Al, eds. Goldman's cedl medicine. 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: 114-116.
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(5.) American Psychiatric Association. Highlights of changes from DSM-IV-TR to DSM-5. http://www.psychiatry.org/Fileu/020Library/Practice/DSM/DSM-5/Changes-from-DSM-W-TR--to-DSM-5.pdf. 2013. Accessed August 22, 2014.
(6.) Edwards BA, O'Driscoll DM, Ali A, et al. Aging and sleep: physiology and pathophysiology. Semin Respir Crit Care Med. 201031(5): 618-633.
(7.) Foley DJ, Monjan AA, Brown SL, et at. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18(6): 425-432.
Irene S. Hong, PharmD, BCPS
Clinical Assistant Professor School of Pharmacy and Pharmaceutical
State University of New York at Buffalo Buffalo, New York
Jeffrey R. Bishop, PharmD, MS, BCPP
University of Minnesota College of Pharmacy Minneapolis, Minnesota
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
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|Date:||Oct 1, 2014|
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