Secondary insomnia in the primary care setting: review of diagnosis, treatment, and management

INTRODUCTION: Insomnia is associated with a number of medical and psychiatric disorders, including chronic pain and clinical depression. Until recently, it was assumed that effective treatment of the underlying medical condition would also correct the sleep disturbance. However, some evidence indicates that treatment of secondary or comorbid insomnia should be considered separately from, and perhaps in addition to, optimizing treatment of the primary condition. METHODS: This article reviews the extant literature to examine the impact of secondary and comorbid insomnia on the patient, and on healthcare economics, in the primary care setting, and discusses current diagnostic and treatment approaches. A MEDLINE search was performed for literature published from 1980 to 2005, and retrieved randomized, controlled clinical trials and key review articles for the conditions most often accompanied by secondary insomnia: depression, chronic pain, and menopause/perimenopause. The search terms included those for commonly used pharmacologic treatments and behavioral therapy. RESULTS: Due to the paucity of clinical trial data in secondary insomnia patients, physicians have had to rely on evidence derived from primary insomnia trials. These data indicate that hypnotic medications are effective in treating sleep onset insomnia. However, few of these agents are effective against the most commonly occurring insomnia symptom - poor sleep maintenance - and many are associated with problematic residual sedation. Nevertheless, the cost of not treating these insomnia symptoms is often greater than the treatment inadequacies. Physicians should thus consider treating what they perceive as secondary insomnia with one of the available forms of therapy. CONCLUSION: Patients experiencing sleep problems associated with a potential medical or psychiatric primary condition would likely benefit from increased physician awareness of secondary insomnia and the subsequent increased attention to diagnosing and treating this prevalent condition. Recommendations for managing secondary or comorbid insomnia in the primary care setting are discussed.     

Pharmacotherapy of insomnia

Introduction: Insomnia is one of the most prevalent sleep disorders in developed countries, being surpassed only by chronic sleep deprivation. Patients with insomnia tend to have an altered quality of life, impaired daytime functioning and an increased risk of work accidents and motor vehicle crashes. Insomnia is commonly associated with chronic medical conditions, metabolic illnesses and mental disorders (such as depression and anxiety), with which there is a dual, reciprocal relationship.

Areas covered: This paper focuses on current pharmacotherapy options for the treatment of insomnia, particularly benzodiazepine receptor agonists, which nowadays represent the mainstay of hypnotic therapy. The melatonin receptor antagonist, ramelteon, is reviewed (an alternative for some patients with only sleep-onset difficulty), as are sedating antidepressants, which are commonly used ‘off-label’ to treat insomnia, despite limited efficacy data and potential significant safety concerns. Orexin (OX) antagonists are also discussed, especially those that block OX2 or both OX1 and OX2 receptors, as these are the most promising new agents for the treatment of insomnia, with encouraging results in preliminary clinical trials.

Expert opinion: Research to evaluate and formulate treatments for insomnia is often complicated by the fact that insomnia is usually of multifactorial etiology. Understanding the molecular and receptor mechanisms involved in promoting sleep in varied disorders could provide future approaches in new drug development. In the long term, more randomized controlled trials are needed to assess both short-term and long-term effects of these medications and their efficacy in comorbid diseases that affect sleep quality or quantity.     

Medical conditions in fibromyalgia patients and their relationship to pregabalin efficacy: pooled analysis of Phase III clinical trials

Objective: Patients with fibromyalgia demonstrate high rates of comorbid somatic and psychiatric disorders. The current post hoc study analyzed the prevalence of comorbid conditions and their relationship to pregabalin efficacy in patients with fibromyalgia pooled from four Phase III clinical trials.

Methods: Patients diagnosed with fibromyalgia according to the American College of Rheumatology criteria, randomized to placebo or 300, 450, or 600 mg/day pregabalin, and with ≥ 1 postbaseline pain score were included. The frequency of comorbid conditions was obtained from patient-reported, voluntary medical histories. Patients were categorized based on the presence of a medical condition (e.g., irritable bowel syndrome) or a group of medical conditions (e.g., neurological disorders). Two efficacy variables were examined within each comorbid category: endpoint changes from baseline in weekly mean pain diary scores (11-point numeric rating scale) and Patient Global Impression of Change.

Results: A large proportion of patients exhibited concomitant headache, immunological (allergy), gastroesophageal, and/or psychiatric disorders. The efficacy analyses performed on these subgroups of patients, amongst others, showed – with few exceptions – consistent pain reductions of similar magnitude with pregabalin.

Conclusion: Comorbid conditions are common among patients with fibromyalgia and their presence is not associated with altered pregabalin efficacy.     

Orexin receptor antagonists – a patent review (2010 to August 2014)

Introduction: The orexin (hypocretin) system is an evolutionarily conserved neuropeptide-G-protein-coupled receptor system, consisting of two neuropeptides the orexin-A and the orexin-B peptides as well as two receptors the orexin-1 and the orexin-2 receptors. The orexin system is crucially involved in the regulation of the circadian rhythm, states of wakefulness and arousal and the modulation of emotions and has attracted the interest of many researchers which resulted in an enormous amount of insight, mainly in the field of antagonists. Clinical proof of concept was obtained with dual orexin receptor antagonists in primary insomnia. Merck’s suvorexant got FDA approval on 13 August 2014 for the treatment of insomnia.

Areas covered: The patent applications from Thomson Reuters Integrity Database (covering 2010 – August 2014) are summarized, analyzed and discussed in the review.

Expert opinion: Intense patenting activities have been observed over the past 3 years in the field of orexin antagonists. Several compounds have been investigated in clinical trials mainly for the treatment of primary insomnia. The advantage of orexin antagonists, based on animal pharmacology results, is the promotion and maintenance of physiological sleep which should avoid hangover phenomena reported as side effects of approved treatments. Many other potential treatment options are mentioned for orexin antagonists of different selectivity profiles.     

Current Phase II investigational therapies for insomnia

Introduction: Insomnia is typified by a difficulty in sleep initiation, maintenance and/or quality (non-restorative sleep) resulting in significant daytime distress.

Areas covered: This review summarizes the available efficacy and safety data for drugs currently in the pipeline for treating insomnia. Specifically, the authors performed MEDLINE and internet searches using the keywords ‘Phase II’ and ‘insomnia’. The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT_2A (ITI-007), melatonin/serotonin5-HT_1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.

Expert opinion: Low-priced generic environments and high development costs limit the further development of drugs that treat insomnia. However, the bidirectional link between sleep and certain comorbidities may encourage development of specific drugs for comorbid insomnia. New insomnia therapies will most likely move away from GABA_AR receptors’ modulation to more subtle neurological pathways that regulate the sleep–wake cycle.     

Orexin receptor antagonists: a review of promising compounds patented since 2006

Importance of the field: The orexin neuropeptide system plays a central role in maintaining arousal and wakefulness. It has been demonstrated that small molecule antagonists to the orexin receptors promote sleep in preclinical species and in patients with insomnia.

Areas covered in this review: This review provides a summary of published patent applications claiming novel orexin antagonists from 2006 to mid-2009, covering both selective and dual orexin receptor antagonists.

What the reader will gain: Readers will gain an overview of orexin biology focusing on genetic and pharmacological validation of this target for treating sleep disorders. Additionally, this review discusses the importance of receptor subtype selectivity and the potential role of subtype selective and dual orexin antagonists in treating psychiatric illnesses beyond insomnia. This review identifies companies that are significant contributors to the patent literature claiming novel orexin receptor antagonists.

Take home message: The study of the orexin system has emerged as one of the key new fields of investigation in neuroscience. The demonstration of clinical proof-of-concept for the treatment of primary insomnia by Actelion in early 2007 has spurred significant interest in this field and competition has markedly increased since 2006.     

A 2-night, 3-period,crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia

ABSTRACT

Objective: To assess the efficacy and safety of ramelteon, a selective melatonin MT₁/MT₂-receptor agonist, for insomnia treatment in older adults.

Methods: In a randomized, 9?week, 3?period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65–83] years) were administered placebo, ramelteon 4?mg, and ramelteon 8?mg in three treatment phases for two consecutive nights. Each phase was separated by 5- to 12?day washout periods. Sleep was monitored via polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire, were recorded, and residual pharmacologic effects were assessed.

Results: Statistically significant reductions in latency to persistent sleep were observed with both ramelteon 4?mg and 8?mg compared to placebo (28.7?min vs. 38.4?min, p < 0.001; 30.8?min vs. 38.4?min, p = 0.005, respectively). Total sleep time (p = 0.036 and p = 0.007,respectively) and sleep efficiency (p = 0.037 and p = 0.007, respectively) were also significantly improved with ramelteon 4?mg and 8?mg compared to placebo. Statistically significant reductions in subjective sleep latency on a Postsleep Questionnaire were reported with ramelteon 4?mg versus placebo (p = 0.037), but not ramelteon 8?mg (p = 0.120); no significant differences on other subjective sleep assessments were reported. A lack of power limits interpretation of self-reported sleep parameters. Incidences of adverse events considered treatment related were placebo (7%), ramelteon 4?mg (11%), and ramelteon 8?mg (5%). No residual pharmacologic effects were observed via Digit Symbol Substitution Test, memory recall tests (immediate and delayed), visual analog scales (feelings and mood), and Postsleep Questionnaire (level of alertness and ability to concentrate).

Conclusions: In older adults with chronic primary insomnia, ramelteon produced significant reductions in latency to persistent sleep and increases in total sleep time and sleep efficacy, and showed no evidence of adverse next-day psychomotor or cognitive effects.     

Pharmacological Treatment of Insomnia Symptoms in Individuals with Substance Use Disorders in Spain: A Quasi-Experimental Study

Introduction: Pharmacological treatment of insomnia in patients with addictions has been hardly investigated and there are few researches about it in an inpatient detoxification. The aim of this study was to describe the outcomes of the pharmacological treatment of insomnia in SUD patients admitted to a detoxification unit in Spain, with a focus on the primary substance of abuse and co-occurring mental disorders. Methods: A quasi-experimental study was conducted in 481 addicted in patients, who were admitted for substances detoxification in Vall d´Hebron University Hospital, Barcelona, Spain, from 2010 to 2015. The patients underwent systematic evaluation of axes I and II psychiatric disorders (SCID-I, SCID-II, and CAADID). Insomnia was evaluated using a night time sleep log. Substance-dependent patients, who had insomnia during hospital detoxification, received a psychotropic medication with hypnotic effect, keeping the regular clinical practice without randomization. Results: At discharge, insomnia was considered to have been alleviated in 63.8% (n = 204) of patients while 36.2% (n = 116) of patients remained with insomnia disturbances. Comparing hypnotic treatments it was observed that mirtazapine and clotiapine were the treatment that corrected the insomnia more frequently. Discussion: Since insomnia is not corrected in all patients, it should be further investigated in medications with hypnotic purpose. Based on the results of this work, randomized clinical trials might be proposed.     

Low-dose doxepin for the treatment of insomnia: emerging data

Background: Doxepin is a tricyclic compound that has been used extensively for the treatment of depressive and anxiety disorders for approximately thirty years. It was noted early to have sedative effects and assist with the improvement of disrupted sleep patterns, but in higher antidepressant doses it was also noted to have significant anticholinergic and antinoradrenergic properties. These properties led to significant dose-limiting side effects, which at times precluded its effective use. Recently, doxepin has seen renewed interest in low doses as an H1 specific antagonist in sleep disorders. Objective: The review seeks systematically to examine currently published data on the use of doxepin for the treatment of insomnia, and its pharmacological basis. Methods: Medline articles showing from a search of ‘doxepin and insomnia’ were included in the review. Results/conclusion: Currently available data support the use of low-dose doxepin as preferential H1 antagonist for the treatment of primary insomnia. There are likely preferential effects upon sleep maintenance insomnia compared with sleep initiation given the role of histamine in the sleep–wake cycle.     

Making sleep easier: pharmacological interventions for insomnia

Introduction: The disorder insomnia represents a relevant and frequent condition in clinical care. Cognitive behavioral therapy of insomnia (CBT-I) is regarded as first line treatment. Pharmacotherapy can be considered if CBT-I is not available or effective. Therefore, pharmacological approaches for disturbed sleep are still among the most widely prescribed pharmacological treatments in clinical care.

Areas covered: In this review, the authors highlight basic physiological pathways of sleep regulation to understand fundamental pharmacological principles of sleep medicine. Available guidelines and reviews are summarized and recommendations formulated regarding the use of benzodiazepines and hypnotic benzodiazepine receptor agonists, melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics and antihistamines, and orexin receptor antagonists in insomnia disorder. Variations in the treatment of insomnia disorder in subpopulations with increased prevalence of sleep disorders – childhood, pregnancy and old age – are specified.

Expert opinion: The well-established off-label use of hypnotic drugs should evocate a debate about a better alignment of clinical practice and scientific evidence and guidelines. Better understanding of sleep regulation could help in the development of completely new substance classes. Focusing subjective sleep disturbances, such as superficial sleep perception might help identify novel pathways.     

女珍颗粒联合佐匹克隆治疗更年期失眠症的临床研究

目的 探讨女珍颗粒联合佐匹克隆片治疗更年期失眠症的临床疗效。方法 选取2016年3月—2018年10月在内蒙古自治区精神卫生中心进行治疗的82例更年期失眠患者为研究对象,根据用药的差别分为观察组（41例）和对照组（41例）。对照组给予佐匹克隆片,7.5 mg/次,1次/d,睡前服用;观察组在对照组基础上口服女珍颗粒,6 g/次,3次/d。两组均治疗4周后进行效果对比。结果 经治疗,对照组有效率为82.92%,显著低于治疗组95.12%（P<0.05）。经治疗,两组患者匹兹堡睡眠质量指数量表（PSQI）评分降低;多导睡眠监测（PSG）中入睡时间、觉醒时间降低,总睡眠时间增加,睡眠效率提高;睡眠结构中I期时间缩短,II、III期及快速动眼期时间延长（P<0.05）,且观察组睡眠情况显著优于对照组（P<0.05）。经治疗,两组患者血清中神经递质去甲肾上腺素（NE）、5-羟色胺（5-HT）、多巴胺（DA）水平显著升高（P<0.05）,且观察组神经递质水平显著高于对照组（P<0.05）。经治疗,两组焦虑自评量表评分（SAS）、抑郁自评量表评分（SDS）、SCL-90、Hamilton抑郁量表（HAMD）评分均显著降低（P<0.05）,且观察组上述评分显著低于对照组（P<0.05）。结论 女珍颗粒联合佐匹克隆片治疗更年期失眠症效果良好,可有效减轻失眠症状,改善患者负面情绪,提高患者生活质量,有着良好临床应用价值。     

Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia

SUMMARY

Objective: Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia. The present study was a randomized, double-blind, multicenter, placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia.

Research design and methods: Patients (n = 308) were randomized to receive placebo or eszopiclone (2?mg or 3?mg) for 44 consecutive nights, followed by 2 nights of single-blind placebo. Efficacy was evaluated with polysomnography (Nights 1, 15 and 29) and patient-reports (Nights 1, 15, 29 and 43/44). Next-day residual effects were evaluated using the Digit-Symbol Substitution Test (DSST).

Results: Eszopiclone 3?mg had significantly less time to sleep onset (?p ≤ 0.0001), more total sleep time and sleep efficiency (?p ≤ 0.0001), better sleep maintenance (p ≤ 0.01), and enhanced quality and depth of sleep (?p < 0.05) across the double-blind period compared with placebo. Eszopiclone 2?mg had significantly less time to sleep onset (?p ≤ 0.001), more total sleep time (?p ≤ 0.01) and sleep efficiency (?p ≤ 0.001), and enhanced quality and depth of sleep (?p < 0.05) compared with placebo, but did not significantly improve sleep maintenance. There was no evidence of tolerance or rebound insomnia after therapy discontinuation. Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group. Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste.

Conclusions: Patients treated with nightly eszopiclone 3?mg had better polysomnographic (through Night 29) and patient-reported measures (through Night 44) of sleep over the 6-week trial. There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST.     

Validation of the sleep impact scale in patients with major depressive disorder and insomnia

Abstract

Objectives: Chronic insomnia and depression are often associated. Measuring the impact on quality of life associated with changes in sleep in co-treatment of insomnia and depression requires a valid and reliable patient reported outcome (PRO) instrument. This study aimed to assess the validity of the Sleep Impact Scale (SIS), a sleep-specific PRO instrument, in a population comorbid with Major Depressive Disorder (MDD) and insomnia to support its use in clinical or clinical trial applications.

Research design and methods: Data from 379 subjects enrolled in a 27 week US, multi-center, phase IV, randomized, double-blind, parallel group, placebo-controlled trial of zolpidem tartrate extended-release taken in combination with escitalopram vs. placebo combined with escitalopram were pooled across treatment groups. Results from multi-trait analyses, tests of internal consistency and test–retest reliability, concurrent validity, known-groups validity, responsiveness, and thresholds for minimal important difference (MID) were examined.

Results: Mean baseline scores on the SIS ranged from 22.85 (±13.41) on Satisfaction with Sleep to 43.49 (±21.12) on Mental Fatigue, reflecting impairments due to sleep problems. The SIS was found to be internally consistent (α?≥?0.70 for all domains) and have good construct validity. The item–domain correlations were ≥0.52 with no instance of an item correlating more highly with a domain other than its own. There were some floor and no ceiling effects. The test–retest reliability of the SIS domains ranged between 0.68 and 0.83. Clinical validity assessed through known groups methods was supported. The SIS was responsive to changes on all domains. Preliminary estimates of minimum important difference (MID) were obtained to interpret changes in SIS domains.

Limitations: Limitations include the need for further qualitative research on content validity and the lack of a patient global assessment of change.

Conclusions: This study yielded adequate evidence of the validity of the SIS for use in clinical trials and research on MDD patients with comorbid insomnia.     

Prolonged-release melatonin for the treatment of insomnia in patients over 55 years

Background: Clinical data show that poor quality, rather than quantity, of sleep corresponds negatively to measures of health, well-being and satisfaction with life. However, until now treatment of insomnia has primarily targeted quantity of sleep. PR (prolonged release)-melatonin offers a new treatment option in insomnia. Objectives: To provide an overview of PR-melatonin, the first melatonin receptor agonist to be granted marketing authorisation in Europe as monotherapy for the treatment of primary insomnia in patients aged > 55 years. Methods: Review data published in peer review journals and the EMEA (European Medicines Agency) website. Results/conclusion: PR-melatonin significantly improves morning alertness and quality of sleep compared with placebo. There are no safety concerns.     

Will insomnia treatments produce overall cost savings to commercial managed-care plans? A predictive analysis in the United States

ABSTRACT

Objective: Research indicates that insomnia may contribute significantly to healthcare costs; however, information on the effects of treatments on costs has not been thoroughly published. This study presents predictive models that forecast, from the perspective of commercial managed care, the effects of insomnia medications in reducing overall medical costs. The main objectives of this study were to predict the level of cost savings associated with insomnia treatments, illustrate the variation in outcomes given underlying model assumptions, and assist managed-care policy-makers with the evaluation of medications routinely administered for insomnia.

Methods: Data on four primary-efficacy measures: wake after sleep onset (WASO), sleep efficiency (SE), sleep onset latency (SOL) and total sleep time (TST) were abstracted from published clinical trial data for eszopiclone, indiplon, low-dose trazodone, ramelteon, zaleplon, zolpidem and zolpidem extended-release. Change in per-patient per-year (PPPY) healthcare costs in a single claims database was calculated for subjects taking zolpidem, zaleplon and low-dose trazodone using generalized linear model (GLM) techniques, controlling for baseline demographics and baseline costs. Change in costs for emerging insomnia medications was forecasted by imputing efficacy values for these drugs into the regressions.

Results: Using the accepted efficacy measure, WASO, zolpidem extended-release had the overall forecasted savings of –$1253 (CI: –$1404 to –$1404) PPPY compared to remaining treatments, whereas ramelteon cost an additional $348 (–$1280 to $584) PPPY. In three out of four cost-efficacy models, zolpidem extended-release had higher mean forecasted PPPY savings.

Conclusion: This study examined cost effects of existing and emerging insomnia medications using models integrating clinical literature and medical claims within a statistical framework. The use of a single database may limit generalizability and models only address a 1?year period. Results suggest treatments can offer health plans direct cost savings, with amounts sensitive to variable and efficacy measures, potentially limited by those variables available in the claims database. Compared to other evaluated treatments, zolpidem extended-release produced consistently higher predicted cost savings.     

A polysomnography study of eszopiclone in elderly patients with insomnia

ABSTRACT

Objective: To evaluate the safety and efficacy of eszopiclone 2?mg in elderly patients (aged 64-86 years) with chronic insomnia.

Methods: This was a randomized, double-blind, placebo-controlled 2‐week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] ≥ 20?min and latency to persistent sleep ≥ 20?min) were randomized to 2 weeks of nightly treatment with eszopiclone 2?mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1–14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis.

Results: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo (?p < 0.05 for all) with a trend in patient-reported morning sleepiness (?p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps (?p = 0.03) and less cumulative naptime (median: 98?min placebo, 70?min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively).

Conclusion: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.     

Pharmacological treatment for insomnia in patients with major depressive disorder

Introduction: Insomnia in Major Depressive Disorder (MDD) is highly prevalent and associated with increased suffering and functional impairment. Effective, evidence-based treatments for insomnia in MDD are an unmet need in clinical practice.

Areas covered: Herein, the authors provide a review of the clinical correlates, putative neurobiological mechanisms and treatment options for the management of insomnia in individuals with MDD.

Expert opinion: Sleep disturbances in MDD should be recognized as at least one of the following: (1) a domain of depressive psychopathology; (2) a consequence of rhythm disruptions; (3) a manifestation of comorbidities of sleep disturbances; (4) a manifestation of the influence of sex hormones in the brain in MDD; (5) a general medical comorbidity; and (6) a side effect of antidepressant medications. Assessment of insomnia in clinical practices is routinely performed with the use of non-structured interviews. Other methods such as standardized questionnaires and sleep diaries, along with complementary methods such as actigraphy and polysomnography are more scarcely applied. Smartphones and personal devices offer a promising strategy with the use of passive, long lasting, and ecologically valid assessments despite the lack of studies specifically targeting insomnia in individuals with MDD. New therapeutic approaches are essential, including novel targets such as orexins/hypocretins and the endocannabinoid system.     

Rebound insomnia in normals and patients with insomnia after abrupt and tapered discontinuation

Rebound insomnia was studied in subjects, aged 25–50 years, with insomnia complaints and normal sleep, insomnia complaints and disturbed sleep, and normal sleep with no complaints (N=21,n=7 per group). Standard sleep recordings were collected on a baseline night and after abrupt discontinuation of 6 nights of 0.50 mg triazolam, tapered discontinuation (3 nights of 0.50 mg, 2 nights of 0.25 mg, and 1 night of 0.125 mg triazolam) and 6 nights of placebo. Significantly disturbed sleep on the discontinuation night compared to the baseline night was found. The relative degree of rebound insomnia was greater in the abrupt condition than in either the tapered or placebo conditions. The tapered condition reduced sleep time by half that of the abrupt condition which was twice the reduction found in the placebo condition. An overall (regardless of group or condition) difference in baseline versus discontinuation sleep was found, suggesting that pill discontinuation itself leads to sleep disturbance. Subjects did not differ in rebound insomnia as a function of pre-existing sleep disturbance.