Sleep disorders. Shelan Karim November 2017
Insomnia refers to difficulty in either falling asleep, remaining asleep or feeling refreshed from sleep. Complaints of poor sleep increase with increasing age and are twice as common in women as in men.
Normal sleep includes two distinct levels of consciousness, orthodox sleep and paradoxical sleep, which are promoted from separate neural centres.
Orthodox sleep normally takes up about 75% of sleeping time. It is somewhat arbitrarily divided into four stages (1–4) which merge into each other, forming a continuum of decreasing cortical and behavioural arousal. Stages 3 and 4 represent the deepest phase of sleep and are also termed slow-wave sleep (SWS).
Paradoxical sleep, rapid eye movement (REM) sleep, normally takes up about 25% of sleeping time and has quite different characteristics to non-rapid eye movement (NREM) sleep. The EEG shows unsynchronised fast activity similar to that found in the alert conscious state and the eyes show rapid jerky movements. Vivid dreams and nightmares most often occur during REM sleep. Normally, stage 4 sleep occurs primarily in the first few hours of the night, while REM sleep is most prominent towards the morning. Brief awakenings during the night are normal. Both SWS and REM sleep are thought to be essential for brain function and both show a rebound after a period of deprivation, usually at the expense of lighter (stage 1 and 2) sleep which appears to be expendable. Many drugs can affect the different stages of sleep.
Benzodiazepines suppress stages 3 and 4 of sleep, but only cause a slight decrease in REM sleep. Z-hypnotics shorten stage 1 of sleep and prolong stage 2 of sleep but have little effect on stages 3, 4 and REM sleep.
CLINICAL PRESENTATION AND DIAGNOSIS
•Patients with insomnia complain of difficulty falling asleep and maintaining sleep.
•Transient (two or three nights) and short-term (<3 weeks) insomnia is common.
•Chronic insomnia (>1 month) may be related to medical or psychiatric disorders or medication.
•Causes of insomnia include stress; jet lag or shift work; pain or other medical problems; mood or anxiety disorders; drug/substance withdrawal; stimulants, steroids, or other medications.
•Difficulty staying asleep is characteristic of depression.
•In patients with chronic disturbances, a diagnostic evaluation includes physical and mental status examinations, routine laboratory tests, and medication and substance abuse histories.
Goals of Treatment
•Correct the underlying sleep complaint
•improve daytime functioning
•avoid adverse drug effects.
•Stimulus control procedures
1.Establish regular times to wake up and to go to sleep (including weekends)
2. Sleep only as much as necessary to feel rested
3. Go to bed only when sleepy. Avoid long periods of wakefulness in bed. Use the bed only for sleep or intimacy; do not read or watch television in bed
4. Avoid trying to force sleep; if you do not fall asleep within 20–30 minutes, leave the bed and perform a relaxing activity (eg read, listen to music, or watch television) until drowsy. Repeat this as often as necessary
5. Avoid daytime naps
6. Schedule worry time during the day. Do not take your troubles to bed
•Sleep hygiene recommendations
1. Exercise routinely (three to four times weekly) but not close to bedtime because this can increase wakefulness
2. Create a comfortable sleep environment by avoiding temperature extremes, loud noises, and illuminated clocks in the bedroom
3. Discontinue or reduce the use of alcohol, caffeine, and nicotine
4. Avoid drinking large quantities of liquids in the evening to prevent nighttime trips to the restroom
5. Do something relaxing and enjoyable before bedtime
Treatment
•Management includes identifying the cause of insomnia, educating about sleep hygiene, managing stress, monitoring for mood symptoms, and eliminating unnecessary pharmacotherapy.
• Transient and short-term insomnia should be treated with good sleep hygiene and careful use of sedative-hypnotics if necessary. Chronic insomnia calls for careful assessment for a medical cause, non-pharmacologic treatment, and careful use of sedative-hypnotics if necessary.
• Antihistamines (eg, diphenhydramine, doxylamine, and pyrilamine) are less effective than benzodiazepines, but side effects are usually minimal. Their anticholinergic side effects may be problematic, especially in the elderly.
• The antidepressants are good alternatives for patients who should not receive benzodiazepines, especially those with depression or a history of substance abuse.
• Amitriptyline, doxepin, and nortriptyline are effective, but side effects include anticholinergic effects, adrenergic blockade, and cardiac conduction prolongation.
• The benzodiazepine receptor agonists are the most commonly used drugs for insomnia. They carry a caution regarding anaphylaxis, facial angioedema, complex sleep behaviors (eg, sleep driving, phone calls, and sleep eating).
•Nonbenzodiazepine GABAA Agonists
•nonbenzodiazepine hypnotics do not have significant active metabolites, and they are associated with less withdrawal, tolerance, and rebound insomnia than the benzodiazepines.
•Zolpidem has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours. Common side effects are drowsiness, amnesia, dizziness, headache, and gastrointestinal (GI) complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist.
•Zaleplon has a rapid onset, a half-life of ~1 hour. It does not reduce nighttime awakenings or increase the total sleep time. It does not appear to cause significant rebound insomnia or next-day psychomotor impairment. The most common side effects are dizziness, headache, and somnolence.
•Eszopiclone has a rapid onset and duration of action of up to 6 hours. The most common adverse effects are somnolence, unpleasant taste, headache, and dry mouth. It may be taken nightly for up to 6 months.
•Benzodiazepines hypnotics
•Benzodiazepines have sedative, anxiolytic, muscle relaxant, and anticonvulsant properties. They increase stage 2 sleep and decrease REM and delta sleep.
•Most benzodiazepines marketed as hypnotics are well absorbed and rapidly penetrate the brain, producing hypnotic effects within half an hour after oral administration. Rates of elimination vary, however, with elimination half-lives from 6 to 100 h
•BENZODIAZEPINE ADVERSE EFFECTS
•Side effects include drowsiness, psychomotor incoordination, decreased concentration, cognitive deficits, and anterograde amnesia which is minimized by using the lowest dose possible.
•Tolerance to daytime CNS effects (eg, drowsiness, decreased concentration) may develop in some individuals.
•Long elimination half-life benzodiazepines are associated with falls and hip fractures.
Potential adverse effects of hypnotic use
•Tolerance and dependence
•Tolerance to the hypnotic effects of benzodiazepines and probably z-hypnotics develops rapidly and may lead to dosage escalation. Nevertheless, poor sleepers may report continued efficacy and the drugs are often used long-term because of difficulties on withdrawal.
•Rebound insomnia, in which sleep is poorer than before drug treatment, is common on withdrawal of benzodiazepines. Sleep latency (time to onset of sleep) is prolonged, intra-sleep wakenings become more frequent and REM sleep duration and intensity are increased, with vivid dreams or nightmares which may add to frequent awakenings. These symptoms are most marked when the drugs have been taken in high doses or for long periods, but can occur after only a week of low dose administration.
•Oversedation and hangover effects Many benzodiazepines used as hypnotics can give rise to a subjective ‘hangover’ effect and after most of them, even those with short elimination half-lives, psychomotor performance, including driving ability and memory, may be impaired on the following day. The risk of fall and confusion increases.
•Drug interactions especially with alcohol or sedative antidepressants, leading to excessive sedation
Sleep Apnea
•Apnea is repetitive episodes of cessation of breathing during sleep.
OBSTRUCTIVE SLEEP APNEA
•Obstructive sleep apnea (OSA) is potentially life threatening and characterized by repeated episodes of nocturnal breathing cessation. It is caused by occlusion of the upper airway, and blood oxygen (O2) desaturation can occur.
•Episodes may be caused by obesity or fixed upper airway lesions, enlarged tonsils, amyloidosis, and hypothyroidism. Complications include arrhythmias, hypertension, and sudden death.
•Heavy snoring, severe gas exchange disturbances, respiratory failure, and gasping occur in severe episodes. Patients with OSA usually complain of excessive daytime sleepiness. Other symptoms are morning headache, poor memory, and irritability.
•The apneic episode is terminated by a reflex action in response to the fall in blood O2 saturation that causes an arousal with resumed breathing.
•Nonpharmacologic approaches are the treatments of choice (eg, weight loss [for all overweight patients], tonsillectomy, nasal septal repair.
CENTRAL SLEEP APNEA
• Central sleep apnea (CSA), less frequent than OSA, is characterized by repeated episodes of apnea caused by temporary loss of respiratory effort during sleep. It may be caused by autonomic nervous system lesions, neurologic diseases, high altitudes, opioid use, and congestive heart failure.
Treatment:
• PAP with or without supplemental O2 improves CSA.
• Acetazolamide causes metabolic acidosis that stimulates respiratory drive and may be beneficial for high altitude, heart failure, and idiopathic CSA.
NARCOLEPSY
• Essential features are sleep attacks, cataplexy, hallucinations, and sleep paralysis. Patients complain of excessive daytime sleepiness, sleep attacks that last up to 30 minutes, fatigue, impaired performance, and disturbed nighttime sleep.
• Cataplexy, which occurs in 70% to 80% of narcoleptics, is sudden bilateral loss of muscle tone with collapse. It is often precipitated by highly emotional situations.
Treatment
• Goals of Treatment: The goal is to maximize alertness during waking hours and improve quality of life.
• Encourage good sleep hygiene and two or more daytime naps daily (as little as 15 min).
• Modafinil, the standard for treatment of excessive daytime sleepiness. Evidence suggests no risk of tolerance, withdrawal, or risk of abuse. Side effects of modafinil include headache, nausea, nervousness, and insomnia.
• Amphetamines and methylphenidate have a fast onset of effect and durations of 3 to 4 hours and 6 to 10 hours, respectively, for excessive daytime sleepiness. Amphetamines have more risk of abuse and tolerance. Side effects include insomnia, hypertension, palpitations, and irritability.
• The most effective treatments for cataplexy are the tricyclic antidepressants, fluoxetine, or venlafaxine.
• Sodium oxybate (a potent sedative-hypnotic) improves excessive daytime sleepiness and decreases episodes of sleep paralysis, cataplexy, and hypnagogic hallucinations.
EVALUATION OF THERAPEUTIC OUTCOMES
• Assess patients with short-term or chronic insomnia after 1 week of therapy for drug effectiveness, adverse events, and adherence to non-pharmacologic recommendations. Patients should maintain a daily recording of awakenings, medications taken, naps, and an index of sleep quality.
• Assess patients with OSA after 1 to 3 months of treatment for improvement in alertness, daytime symptoms, and weight reduction. The bed partner can report on snoring and gasping.
• Pharmacotherapy monitoring parameters include reduction in daytime sleepiness, cataplexy, hypnagogic and hypnopompic hallucinations, and sleep paralysis. Assess patients regularly during medication titration, then every 6 to 12 months for side effects (eg, hypertension, sleep disturbances, and cardiovascular abnormalities).