Non-benzodiazepine Sedative-hypnotics Research Articles

Trends in Insomnia Diagnosis and Treatment Among Medicare Beneficiaries, 2006–2013

ObjectiveInsomnia is an important clinical problem affecting the elderly. We examined trends in insomnia diagnosis and treatment among Medicare beneficiaries over an eight-year period. MethodsThis was a time-series analysis of Medicare administrative data for years 2006–2013. Insomnia was defined as the presence of at least one claim containing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 307.41, 307.42, 307.49, 327.00, 327.01, 327.09, 780.52, or V69.4 in any given year. Insomnia medications were identified by searching the Part D prescription drug files in each year for barbiturates, benzodiazepines, chloral hydrate, hydroxyzine, nonbenzodiazepine sedative hypnotics, and sedating antidepressants. ResultsPrevalence of physician-assigned insomnia diagnoses increased from 3.9% in 2006 to 6.2% in 2013. Prevalence of any insomnia medication use ranged from 21.0% in 2006 to 29.6% in 2013 but remained steady. A sharp increase in use of benzodiazepines from 2012–2013 (1.1% to 17.6%) drove up total insomnia medication use for 2013. Prevalence of both insomnia diagnosis and medication use ranged from 3.5% in 2006 to 5.5% in 2013, while prevalence of either insomnia diagnosis or medication use ranged from 22.7% in 2006 to 31.0% in 2013. ConclusionIn this large national analysis of Medicare beneficiaries, prevalence of physician-assigned insomnia diagnoses was low but increased over time. Prevalence of insomnia medication use was up to four-times higher than insomnia diagnoses and remained steady over time. Notably, prevalence of benzodiazepine use increased dramatically from 2012–2013 after these medications were included in the Medicare Part D formulary.

0411 Trends in Insomnia Prescription MedicTrends in Insomnia Prescription Medication Use Among Medicare Beneficiaries, 2006–2013

Traditional pharmacotherapy for insomnia has known adverse outcomes among older adults, including falls and cognitive impairment. However, few studies have characterized longitudinal insomnia-related medication trends among Medicare beneficiaries. These characteristics are of particular interest given the recent (2012) inclusion of benzodiazepines in the Medicare prescription drug formulary. The objective of this study was to characterize trends in insomnia-related prescription medication use among Medicare beneficiaries over a seven-year period. We conducted a time-series analysis to estimate the annual prevalence of use of insomnia medications using a 5% sample of Medicare fee-for-service beneficiaries from 2006–2013. Insomnia medication use (defined as at least 1 fill annually) was identified by searching the Part D prescription drug claims and included insomnia-related medication classes and drugs: barbiturates, benzodiazepines, chloral hydrate, hydroxyzine, non-benzodiazepine sedative hypnotics (NBSH), and sedating anti-depressants. Prevalence of insomnia medication use ranged from 20.8% in 2006 to 23.4% in 2013 (p>.10). Benzodiazepine use increased from 0.5% in 2012 to 8.0% in 2013 (p = 0.03). Use of sedating antidepressants and NBSH decreased modestly from 9% and 8%, respectively, in 2006 through 2013. Prevalence of sedating antidepressant, NBSH, and hydroxyzine use was higher among women than men (p<0.001 for all). Benzodiazepine and sedating antidepressant use was most common among those age <65 and ≥85 years. NBSH use was most common among those age <65 years. Use of all drugs was similar among those ages 65 - 74 years and 75 - 84 years. Prevalence of insomnia medication use remained high among Medicare beneficiaries from 2006 - 2013, particularly among women. Benzodiazepine use increased sharply following inclusion in the Medicare formulary. Future studies should examine population-level outcomes associated with this increased use of benzodiazepines. Merck Investigator Initiated Studies Program (PI: Wickwire).

Eszopiclone and Zolpidem Do Not Affect the Prevalence of the Low Arousal Threshold Phenotype.

We sought to determine whether non benzodiazepine sedative hypnotics (NBSH) reduce the occurrence of the low arousal threshold (LAT) phenotype. Consecutive patients with suspected obstructive sleep apnea (OSA) referred for polysomnography (PSG) had demographic and PSG data abstracted. LAT was estimated using PSG criteria. After adjusting for pretest probability (PTP) for OSA, we calculated the effect that premedication with NBSHs has on LAT prevalence. Five hundred seventy-nine patients with a mean age and body mass index of 42.2 ± 10.1 y and 28.9 ± 4.5 kg/m2, respectively, had data available for analysis. Most patients (444, or 80.9%) had a LAT, and administering a NBSH (zolpidem or eszopiclone) on the same night as the PSG did not change LAT prevalence (NBSH: 339 (83.3%) versus no drug: 100 (80.6%); p = 0.50). Adjusting for PTP, neither administration of eszopiclone (odds ratio 0.80 (95% confidence interval: 0.33-2.0); 0.69) nor zolpidem (odds ratio 1.65 (95% confidence interval: 0.8-3.5); p = 0.19) reduced the odds that a patient had a LAT. NBSHs did not change the mean SpO2 nadir, percentage hypopneas, or apnea-hypopnea index. There was no association between zolpidem or eszopiclone dosing and SpO2 nadir (zolpidem: β = -0.69, p = 0.80; eszopiclone: β = -1.53, p = 0.68), percentage hypopneas (zolpidem: β = 2.2, p = 0.43; eszopiclone β = -6.2, p = 0.46), or apnea-hypopnea index (zolpidem: β = 3.1, p = 0.22; eszopiclone: β = 2.6, p = 0.39). The LAT is common in our population and NBSH premedication does not alter its occurrence. Further studies are needed to determine how the LAT can be optimally managed to improve OSA treatment.

Nonbenzodiazepine Sedative Hypnotics and Risk of Fall-Related Injury.

The objective of this study was to test the hypothesis that use of zolpidem, eszopiclone, and zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture. We conducted a case-crossover study on a 5% random sample of Medicare beneficiaries age 65 y or older hospitalized with either TBI (n = 15,031) or hip fracture (n = 37,833) during 2007-2009. Use of zolpidem, eszopiclone, or zaleplon during the 30-day period prior to injury hospitalization was compared to use during four control periods at 3, 6, 9, and 12 mo prior to injury. The primary outcome was hospitalization for TBI or hip fracture. Zolpidem use during the month prior to injury was associated with increased risk of TBI (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.56, 2.25); however, eszopiclone use during the same period was not associated with increased risk (OR 0.67; 95% CI 0.40, 1.13). Zolpidem use during the month prior to injury was associated with increased risk of hip fracture (OR 1.59; 95% CI 1.41, 1.79); however, eszopiclone use during the same period was not associated with increased risk (OR 1.12; 95% CI 0.83, 1.50). Analysis of zaleplon use in the month prior to injury was limited by low drug utilization but was not associated with increased risk of TBI (OR 0.85; 95% CI 0.21, 3.34) or hip fracture (OR 0.92; 95% CI 0.40, 2.13) in this study. For the treatment of insomnia in older adults, eszopiclone may present a safer alternative to zolpidem, in terms of fall-related injuries.

Management of late-life insomnia

IntroductionInsomnia is the most frequent sleep disorder in late life. Forty-two percent of elderly people in the United States often complain about difficulties to get or maintain sleep, or awakening too early. Insomnia is frequent in old people greatly due to frequency of concomitant medical illnesses and polypharmacy, rather than because of age.ObjectivesThe objective of our research was to revise the current state of knowledge about management of insomnia in people above 65 years of age.MethodologyFor that, a bibliographical search through PubMed.gov has been made. From the obtained results, the 14 which best suited for our goals were selected, 10 of them dealing with people above 65 years and the rest with people above 75 or 80 years of age.ResultsBased on the literature reviewed, the current options of management of late-life insomnia are based on behavioral or pharmacological therapy. The combination of behavioral therapies shows results and is currently considered as an option, especially given the possibility of medicine interaction and the secondary effects hypnotic and sedative medicines might produce. There is a paucity of long-term safety and efficacy data for the use of non-benzodiazepine sedative-hypnotics. There are no criteria for the use of antidepressant sedatives in elderly people without diagnosed depression, although they are still used in practice.ConclusionPossibility of using behavioral therapy as first option. In case of polymedicated or multi-pathological patients, pay special attention when starting a pharmacological treatment, choose the most suitable one and supervise it closely.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Safety analysis of zolpidem in elderly subjects 80 years of age or older: adverse event monitoring in Japanese subjects

Objectives: Prescriptions of non-benzodiazepine sedative hypnotics, e.g. zolpidem, for insomnia in elderly subjects 80 years of age or older have markedly increased in the USA. However, a meta-analysis of the risks and benefits of hypnotics in older people reported the benefits associated with hypnotics use are outweighed by the risks. This study aimed to investigate the safety of zolpidem administration in extremely old elderly.Methods: The prevalence of adverse reactions to zolpidem was investigated in a subpopulation of participants in the Drug Event Monitoring project of the Japan Pharmaceutical Association. A total of 1011 (316 males and 695 females) zolpidem users, including 261 (25.8%) subjects 80 years of age or older without cognitive or mental complications, were eligible for the analysis.Results: The elderly and female patients were prescribed significantly lower doses of zolpidem than their counterparts. Adverse symptoms after the last prescription were reported by 60 (5.9%) subjects. The most common symptoms were impaired balance and/or falls (1.8%) and morning drowsiness (1.3%). The multiple logistic regression analyses showed that subjects 80 years of age or older were at lower risk of adverse symptoms (odds ratio 0.39, 95% confidence intervals: 0.17–0.88).Conclusion: Our findings in a real-world clinical setting suggest that low-dose zolpidem can be safely prescribed to subjects 80 years of age or older without cognitive or mental complications.

Potentially inappropriate medications in older adults: A review of the 2012 Beers Criteria and the implications in persons with dementia

In 2012, the American Geriatrics Society (AGS), along with a panel of 11 experts, updated the Beers Criteria which has evolved significantly since its inception in 1991. The Beers Criteria, in general, classifies medications/medication classes as: (1) potentially inappropriate for use in all older adults, (2) potentially inappropriate for older adults with certain diseases or symptoms and (3) requiring extra caution when used in older adults. Although each patient must be evaluated individually, the Beers Criteria is a useful clinical tool that can be used when initiating pharmacologic agents in both ambulatory and institutionalized patients. The concept behind use of the Beers Criteria is that it allows prescribers to readily identify, and avoid, medications associated with negative outcomes in older adults therefore decreasing the risk of adverse drug events (ADEs). Within this review article, there will be a highlight of potentially inappropriate medications (PIMs) commonly seen in clinical practice settings such as antipsychotics, benzodiazepines, non-benzodiazepine sedative-hypnotics, anticholinergics and sliding scale insulin. The focus will be to outline the risk-benefits of these drug classes within the context of persons with dementia. Furthermore, the use of PIMs has both clinical and financial implications in Medicare Star ratings and Healthcare Effectiveness Data and Information Set (HEDIS) measures.

Use of non-benzodiazepine sedative hypnotics and risk of falls in older men.

To ascertain whether use of non-benzodiazepine sedative-hypnotics is associated with risk of falls and compare this to risk of falls associated with use of benzodiazepines. Among 4450 community-dwelling men, aged 71 years and older, enrolled in the population-based prospective cohort study, Osteoporotic Fractures in Men (MrOS), use of nonbenzodiazepine sedative-hypnotics and benzodiazepines was assessed by interview and verified from medication containers at the third annual visit of the MrOS study. Falls in the subsequent one-year period were ascertained by tri-annual questionnaires and a computerized dictionary used to categorize type of medication. In age-adjusted models, non-benzodiazepine sedative hypnotic use was associated with an increased risk of any falls (one or more falls) (RR 1.44, 95% CI 1.15, 1.81) and recurrent falls (2 or more falls) (RR 1.51, 95% CI 1.07, 2.14). Use of benzodiazepines was associated with a similar increase in age-adjusted risk of falling. Depressive symptoms, inability to stand from a chair, and instrumental activities of daily living (IADL) impairment modestly attenuated these associations. The association between non-benzodiazepine sedative-hypnotic use and falls was most pronounced among men without a history of falls in the previous year: in a multivariable model controlling for multiple potential confounders, the RR of any falls was 1.74 (95% CI 1.13, 2.68) in this subgroup. Use of non-benzodiazepine sedative-hypnotics is associated with an increased risk of falls. Non-pharmacologic approaches to sleep disturbances may represent the safest approach to sleep difficulties in older adults.

Hong Kong Poison Information Centre: Annual Report 2008

Objective To report the poisoning data of Hong Kong Poison Information Centre (HKPIC) in 2008. Methods From 1st January 2008 to 31st December 2008, all poisoning cases received by HKPIC were retrieved from its database (DATOX &amp; PIC-MS) for analysis. Results 4,029 poisoned cases were analyzed. There were 1,755 male patients (43.6%) and 2,262 female patients (56.1%). Nearly two-thirds of them were between 20 and 59 years old. Common causes of exposure were suspected self harm/suicidal attempt, unintentional exposure and abusive use. Sedatives, household products, paracetamol, and ketamine were common poisons exposed and non-benzodiazepine sedative-hypnotics were involved in about one-seventh of the poisoning cases. The majority of the patients were managed conservatively, with 6.0% and 5.9% treated by decontamination and antidotes respectively. Most cases had uneventful recovery; about 1% of the poison exposure resulted in death and about 5% of the exposure had major outcomes. Conclusions This annual report provides updated epidemiological information on poisoning in Hong Kong in 2008 and highlights some changes in comparison with our previous reports. The increase in abusive substance poisoning, in particular ketamine, requires further attention.

An Unusual Cause of Insomnia Following IED-Induced Traumatic Brain Injury

A 20-year-old man presented to the sleep disorders clinic for evaluation of recurrent episodes of sleeping difficulties and a diagnosis of insomnia made by his primary care physician. Approximately 6 months prior to his initial presentation, he sustained multiple injuries following an improvised explosive device (IED) blast while serving in Operation Iraqi Freedom, including a mild-moderate traumatic brain injury and penetrating injuries to both eyes. His ophthalmologic trauma resulted in enucleation of his right eye and significantly reduced vision in his left. Since his injuries, he reports recurrent periods during which he is unable to initiate sleep at a desired time. During these periods, he experiences significant fatigue and daytime somnolence when trying to keep a normal sleep-wake schedule. He stated that these periods resolved slowly but then recurred without an identifiable precipitating cause. He had no significant past medical history and denies any sleep complaints prior to his injury. He was diagnosed with depression but stated that his symptoms worsened after starting a selective-serotonin reuptake inhibitor. Similarly, non-benzodiazepine sedative-hypnotics did not significantly improve his insomnia and resulted in worsening of his daytime fatigue. Physical examination demonstrated an enucleated right eye and left visual acuity of 20/200, but was otherwise unremarkable; laboratory studies, including thyroid function testing, a complete blood count, and serum electrolytes were within normal limits. Nocturnal polysomnography revealed a sleep latency of 42 minutes, sleep efficiency of 96%, and preserved sleep architecture. The patient completed a sleep diary over the course of a month (Figure 1). Treatment was then initiated, and the patient reported marked improvements in sleep latency, sleep consolidation, and daytime sleepiness during a follow-up evaluation two months later. A repeat sleep diary showed normalization of his sleep-wake cycle (Figure 2). Figure 1 Sleep diary pre-treatment. Figure 2 Sleep diary post-treatment. Q: WHAT IS THE DIAGNOSIS AND HOW WOULD YOU INITIATE THERAPY? A: CIRCADIAN RHYTHM SLEEP DISORDER, FREE-RUNNING TYPE (NON–24-HOUR SLEEP WAKE SYNDROME). BOTH EVENING MELATONIN ADMINISTRATION AND MORNING PHOTOTHERAPY HAVE BEEN SHOWN TO IMPROVE SYMPTOMS.

Indiplon: A Nonbenzodiazepine Sedative–Hypnotic for the Treatment of Insomnia

To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of indiplon in the treatment of transient and chronic insomnia in adult and geriatric patients. A literature search was conducted using MEDLINE (1966-May 2008), International Pharmaceutical Abstracts (1970-May 2008), and Cochrane database (2007) for the key words indiplon or NBI-34060. References cited in the articles were reviewed for additional information. Abstract data were included only in the absence of significant published data. English-language literature reporting animal and human clinical studies was reviewed to evaluate data on the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of indiplon. Clinical trials selected for inclusion were limited to those with human subjects, with the accepted inclusion of pharmacology data in animals. Indiplon is a nonbenzodiazepine sedative-hypnotic that exhibits its sedating activity through its interaction with the gamma-aminobutyric acid alpha receptor complex. Indiplon immediate-release (IR) as well as modified-release (MR) forms have shown improvement compared with placebo in patients with DSM-IV-TR primary insomnia in various areas of subjective and objective sleep measurements. Specifically, improvements in total sleep time, latency to persistent sleep, latency to sleep onset, wake after sleep onset, and sleep quality have been noted in clinical trials. Trials evaluating both indiplon IR and MR have so far not identified any major serious adverse effects. Limited clinical trial data exist on use of indiplon in a "true" transient insomnia patient population. Based on recent Food and Drug Administration requests, clinical trial data assessing direct comparisons of indiplon IR with other approved nonbenzodiazepine sedative-hypnotics are needed to clearly define the differences among these agents.

Management of chronic insomnia in elderly persons

Background: Chronic insomnia is common among the elderly These elderly patients are often viewed as difficult to treat, yet they are among the groups with the greatest need of treatment. Objective: This article reviews the literature on the management of chronic insomnia in elderly persons. Methods: A search of MEDLINE was conducted for articles published in English between January 1966 and March 2006 using the terms insomnia, behavioral therapy, estsazolsam, fluvsazepsam, qusazepsam, teMsazepsam, tvisazolsam, eszopiclone, zaleplon, zolpidem, mirtazapine, nefazodone, trazodone, and ramelteon. Articles were selected if they were meta-analyses or evidence-based reviews of therapeutic modalities; randomized controlled trials of nonpharmacologic or pharmacologic treatment; or review articles covering the characteristics and management of insomnia. Preference was given to meta-analyses, evidence-based reviews, and articles that included relevant new information. Results: Available options for the treatment of insomnia include nonpharmacologic approaches, foremost among them cognitive behavioral therapy, and pharmacotherapies, including chloral hydrate, barbiturates, over-the-counter (OTC) and prescription antihistamines, OTC dietary supplements (including melatonin), sedating antidepressants, benzodiazepine and nonbenzodiazepine sedative-hypnotics, and melatonin agonists. There is considerable evidence to support the effectiveness and durability of nonpharmacologic interventions for insomnia in adults of all ages, yet these interventions are underutilized. With some recent exceptions, the majority of identified studies of pharmacotherapy were of short duration (≤6 weeks) and did not exclusively enroll older adults. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. Newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Conclusions: Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. More research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.

Psychotropic Medications and Risk for Falls Among Community-Dwelling Frail Older People: An Observational Study

Injuries due to falls are one of the most important public health concerns for all ages, but especially for frail elderly people. Although a small number of falls have a single cause, the majority have many different causes resulting from the interactions between intrinsic or extrinsic risk factors. We conducted an observational study on data from a large population of community-dwelling elderly people to tests the hypothesis that the current use of different classes of psychotropic medications, including antipsychotic agents, benzodiazepines, nonbenzodiazepine sedative-hypnotics, and antidepressants, increases the risk for falls. We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs (n = 2854). After adjusting for all potential confounders, users of any psychotropic drugs had an increased risk of fall of nearly 47% (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.24-1.74). Similarly, compared with nonusers, users of atypical antipsychotic drugs also had an increased risk of falling at least once (OR, 1.45; 95% CI, 1.00-2.11). Among benzodiazepine users, patients taking agents with long elimination half-life (OR, 1.45; 95% CI, 1.00-2.19) and patients taking benzodiazepines with short elimination half-life (OR, 1.32; 95% CI, 1.02-1.72) had an increased risk of falls. Patients taking antidepressants did not show a higher risk of falling compared to nonusers (OR, 0.92; 95% CI, 0.83-1.41). Our data suggest that, among psychotropic medications, antipsychotic agents and benzodiazepines are associated with an increased risk of falls. Our findings do not support the hypothesis that preferential prescribing of short-acting benzodiazepines instead of long-acting agents or atypical antipsychotic medications instead of typical agents will substantially decrease fall risk associated with the use of these classes of drugs.

The benzodiazepine site of the GABA A receptor: an old target with new potential?

The gamma-aminobutyric acid-A (GABA A) receptors is the target for the most widely prescribed sleep medicines. It is a ligand-gated ion channel, activated by the amino acid neurotransmitter GABA, which normally results in hyperpolarization of neurons leading to reduced action potential firing, and thereby a reduction in neuronal activity. It has a rich pharmacology with a number of separate modulator binding sites. The best studied of these is the benzodiazepine site. Modulation of GABA A receptor activity by benzodiazepines produces sedative, hypnotic, anxiolytic and anticonvulsant activities. Short half-life benzodiazepines such as triazolam have been particularly useful in treating insomnia, but concerns have been raised regarding tolerance potential and dependence liability of classical benzodiazepines, which has led to reduced prescribing of these agents. In recent years, the treatment of sleep disorders has moved towards the use of non-benzodiazepine sedative hypnotics. These agents act at the same site on the GABA A receptor, but feature less of the problems associated with classical benzodiazepines. Recent progress in our understanding of the diversity and pharmacology of GABA A receptor subtypes has provided a rational explanation for the efficacy of these compounds. Findings from preclinical studies reveal promising avenues for the design of better therapeutics in the near future.

The nuts and bolts of behavioral therapy for insomnia

Chronic insomnia is common among the elderly These elderly patients are often viewed as difficult to treat, yet they are among the groups with the greatest need of treatment.This article reviews the literature on the management of chronic insomnia in elderly persons.A search of MEDLINE was conducted for articles published in English between January 1966 and March 2006 using the terms insomnia, behavioral therapy, estsazolsam, fluvsazepsam, qusazepsam, teMsazepsam, tvisazolsam, eszopiclone, zaleplon, zolpidem, mirtazapine, nefazodone, trazodone, and ramelteon. Articles were selected if they were meta-analyses or evidence-based reviews of therapeutic modalities; randomized controlled trials of nonpharmacologic or pharmacologic treatment; or review articles covering the characteristics and management of insomnia. Preference was given to meta-analyses, evidence-based reviews, and articles that included relevant new information.Available options for the treatment of insomnia include nonpharmacologic approaches, foremost among them cognitive behavioral therapy, and pharmacotherapies, including chloral hydrate, barbiturates, over-the-counter (OTC) and prescription antihistamines, OTC dietary supplements (including melatonin), sedating antidepressants, benzodiazepine and nonbenzodiazepine sedative-hypnotics, and melatonin agonists. There is considerable evidence to support the effectiveness and durability of nonpharmacologic interventions for insomnia in adults of all ages, yet these interventions are underutilized. With some recent exceptions, the majority of identified studies of pharmacotherapy were of short duration (≤6 weeks) and did not exclusively enroll older adults. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. Newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people.Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. More research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.