Insomnia Final

The Consultant ImprovingR patient care through drug education June 2006 Volume XV Number 6 Insomnia Christine M. Cheng, Pharm.D and Adara S. Louis, Pharm.D. Guest Editor: Julie A. Dopheide, Pharm.D., BCPP OVERVIEW Insomnia is defined as a complaint of disturbed, inadequate The Bottom Line or poor-quality sleep that interferes with daytime functioning. • Nondrug therapy is the preferred treatment for Individuals with insomnia may have difficulty falling or staying chronic insomnia. Sleep medications are often asleep, or feel unrefreshed from sleep despite having adequate used in addition to nondrug therapies and in opportunity to sleep. Up to half of all adults complain of occa- patients who do not respond to these methods. sional trouble sleeping in any given year. About 10-25% have • Sleep medication should be selected based on the chronic symptoms with serious daytime consequences, including underlying sleep problem (e.g., difficulty falling fatigue, difficulty concentrating, irritability, and memory impair- asleep vs. staying asleep) and any underlying ment.1-3 Insomnia is more common among women, the elderly, medical causes of insomnia. 4 and patients with medical or psychiatric conditions. People • Medications with a fast onset and short duration with chronic insomnia have lower motivation and productivity, are the best choices for difficulty falling asleep are more likely to have depression or anxiety, and are at greater (sleep onset insomnia). Appropriate drugs may risk for injury (falls, traffic accidents) and substance abuse than include zaleplon, zolpidem immediate-release, people without insomnia.5,6 Early recognition and treatment of triazolam and ramelteon. Rebound insomnia can insomnia can reduce its physical and emotional toll, as well as be a problem, however, with short acting healthcare costs related to its complications. benzodiazepines like triazolam. Management of insomnia varies widely and depends on the • Individuals who have difficulty staying asleep (sleep cause, duration and frequency of symptoms. Recognizing and maintenance insomnia) are most appropriately mitigating any underlying cause is an essential first step in suc- treated with drugs that have an intermediate cessful treatment. Nondrug therapies include sleep hygiene duration and no active metabolites (to minimize measures (correcting poor sleep habits) and cognitive-behavioral daytime effects). Zolpidem extended-release, eszopiclone, temazepam, oxazepam, lorazepam therapy, which combines correcting negative beliefs and attitudes and estazolam may be appropriate choices. about sleep with behavioral changes that improve sleep. If nec- Zaleplon can be taken after awakening in the night. essary, medications are added. Drugs used for insomnia include • Sedative-hypnotics should be used intermittently, in over-the-counter antihistamines, benzodiazepines, selective ben- the lowest effective doses, for a short duration, with zodiazepine receptor agonists, sedating antidepressants, and the gradual discontinuation to avoid rebound insomnia, melatonin receptor agonist ramelteon. dependence, and withdrawal symptoms. Continuing Education Objectives ACPE# 428-000-06-006-H01 CA BRN # 13118 Benzodiazepines are effective and safer than • Describe the difference between sleep onset and sleep mainte- older hypnotics (e.g., barbiturates, chloral hy- nance insomnia, and primary and secondary insomnia. drate) but have several disadvantages including • List the drugs commonly used for the treatment of insomnia. residual daytime sedation, tolerance, depen- Describe the efficacy and most concerning adverse effects of dence and withdrawal symptoms, rebound in- each drug class. somnia and abuse potential. The newer benzo- • Describe nondrug therapies for the treatment of insomnia. diazepine receptor agonists (zolpidem, zaleplon, eszopiclone) are generally the preferred agents • Given a patient’s symptoms, recommend a medication for insomnia. for uncomplicated insomnia, since they have a 1 lower risk of dependence, withdrawal symptoms and drugs such as alcohol and caffeine, and drugs of abuse abuse. The newer agents are comparable to benzodiaz- may also cause insomnia. (Table 1)6,8,10 epines in the treatment of sleep onset insomnia (difficulty falling asleep). Few comparative studies in sleep Nondrug Management maintenance insomnia (wakefulness after sleep onset) Sleep experts recommend nondrug approaches as the have been published. The newer drugs are more expen- preferred treatment for insomnia because of their effi- sive than benzodiazepines. Ramelteon is modestly effec- cacy, long lasting benefits, and lack of side effects.2,3,10 tive for sleep onset insomnia and has no potential for Nondrug approaches include both behavioral and cogni- dependence or abuse. Sedating antidepressants (e.g., tive therapy. Behavioral therapies such as stimulus con- trazodone, amitriptyline) are often prescribed off-label to trol, sleep restriction, sleep hygiene education, and relax- avoid the potential for dependence, withdrawal and ation training have been in use for decades. An analysis abuse with benzodiazepine agonists, however, their of 48 clinical trials of behavioral therapies found that 70- value has been demonstrated mainly in patients with 80% of patients with primary chronic insomnia have im- depression. provements in sleep onset, sleep maintenance and total sleep time.10 The most effective behavioral strategies ap- Background pear to be stimulus control and sleep restriction.2 Stimu- lus control is aimed at reassociating the bedroom with Insomnia may be transient (lasting < 1 week), short term the rapid onset of sleep. (See inset, Patient Connection) 7 (lasting 1-4 weeks) or chronic (lasting > 1 month). Tran- Sleep restriction minimizes excessive time in bed in or- sient and short-term insomnias are usually related to der to increase sleep efficiency (the ratio of time spent emotional or physical discomfort from stressors such as asleep to time spent in bed). More time in bed is al- acute illness, environmental changes (noise, light, tem- lowed as the time asleep increases, and time in bed is perature), anticipation of a stressful event, or sleeping at reduced if the time asleep decreases. a time inconsistent with the daily biological rhythm (e.g., jet lag or shift work).8,9 More recently, researchers have tested cognitive methods designed to correct anxiety-producing and erroneous Chronic insomnia often has multiple underlying causes beliefs about sleep (e.g., "I can't sleep without medica- and is more challenging to treat. Symptoms may wax tion."). There is evidence that combined cognitive and and wane over time. Primary chronic insomnia arises behavioral therapy (CBT) can be as effective as prescrip- from no identifiable environmental, medical or psychiat- tion drugs for the treatment of chronic insomnia.1,11 In ric cause and accounts for 12-15% of people with chronic contrast to sleep medications, the benefits of CBT persist 2,7 insomnia. Secondary or comorbid insomnia develops as for 6 months or more after treatment is completed and a consequence of an underlying medical problem (e.g., no adverse effects have been identified.2,11 Potential pain, immobility, difficulty breathing), psychiatric illness drawbacks are the need for a trained therapist and a mo- (e.g., dementia, anxiety, depression), or specific sleep tivated patient, the cost of therapy, and a delayed onset disorder (e.g., restless legs syndrome, periodic limb of effect (several weeks) compared to sleep medication. movement disorder, sleep apnea ). Medications, social Table 1. Some Drugs That May Worsen Insomnia Drugs That May Cause Insomnia Drugs That May Produce Withdrawal Insomnia Alcohol Antihypertensives (cont.) Decongestants Levodopa Alcohol Miscellaneous Antidepressants Diuretics (at bedtime) phenylephrine Methylphenidate Antihistamines Amphetamines Methyldopa pseudoephedrine Methysergide Bupropion Hypnotics Cocaine Reserpine Nicotine Monoamine oxidase Miscellaneous Barbiturates Marijuana Oral contraceptives inhibitors Hypnotic use (chronic) Anabolic steroids Benzodiazepines Opiates Serotonin reuptake Phenytoin Phencyclidine Sympathomimetic amines Antineoplastics Chloral hydrate inhibitors Quinidine Amphetamines Caffeine Ethchlorvynol Tricyclic antidepressants Theophylline Appetite suppressants Corticosteroids Monoamine oxidase Venlafaxine Thyroid preparations Beta-adrenergic Histamine2-receptor inhibitors antagonists Antihypertensives agonists Tricyclic antidepressants Beta-blockers 2 Patients should also be encouraged to have proper sleep elderly or debilitated individuals and those with liver hygiene. (See inset, Patient Connection) Since nondrug disease. treatments require behavioral change and can take sev- Older people are more susceptible to benzodiazepine eral weeks to work, the risk of low compliance should be side effects.16 The use of long-acting agents such as evaluated. Drug therapy may be added in the interim if flurazepam has been linked with an increased risk of necessary. Combination therapy with a sedative-hyp- falls and hip fractures in the elderly.17 The use of seda- notic plus CBT or behavioral therapy is common, but tive hypnotics in older people with insomnia generally has not been well studied. results in modest benefits and a relatively high risk of side effects. These include cognitive impairment, day- Prescription Sleep Medications time fatigue and psychomotor dysfunction, which may Benzodiazepine Receptor Agonists lead to falls and traffic accidents. The benefits

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