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*Insomnia            2000.11.14 nishitarumizu  Up to one third of patients seen in the primary care setting experience occasional difficulties in sleeping, and up to 10 percent of patients have chronic sleep problems. Although insomnia is rarely the chief reason for an office visit, its detection may be enhanced by incorporating sleep-related questions into the general review of patient systems. Sleep disturbance is a reliable predictor of psychologic ill health, physical ill health, or both. Thus a report of disturbed sleep signals the need for further evaluation. Natural History of Sleep With aging, the total amount of sleep shortens. Delta sleep (stages 3 and 4 sleep), the deepest and most refreshing kind of sleep, diminishes markedly with age. In contrast, early stage 1 sleep, the lightest sleep, increases with age. These features help explain why sleep in old age becomes more fragmented, with more brief awakenings. There is little decline in REM sleep throughout a person's lifetime. Even though sleep is shorter in duration, shallower and more fragmented in the elderly, poor sleep is not an inevitable consequence of aging, and elderly persons do not necessarily require less sleep than younger persons. Also, constant daytime drowsiness or early-morning awakening should not be considered normal changes of aging. Epidemiology and Prevalence In a survey of office-based physicians in the United States, patients with insomnia had also been diagnosed with comorbid depression (30% of total), other mental diseases (20%) and organic disorders (19%); thus, only 31% of the sample were determined to have primary insomnia. A population-based survey using a structured DSM-III-based diagnostic questionnaire, 811 (10.2%) of the 7954 respondents complained of insomnia, and of those, 328 (40.4%) had a comorbid psychiatric disorder - most met the criteria for either anxiety or depression. For those with insomnia that persisted over a 12-month period, compared with those without insomnia, the risk of developing new major depression (odds ratio [OR] 39.8; 95% confidence interval [CI] 19.8-80.0), anxiety disorder (OR 25.6) or alcohol dependence (OR 3.4) was much higher. Evaluation of Insomnia A wide range of disorders should be considered in the search for an underlying cause of chronic insomnia. (Table 1) The etiology of primary insomnia relates in part to psychologic conditioning processes. Most cases of insomnia develop initially in response to a medical or psychosocial stressor. As sleeplessness persists, the patient begins to associate the bed with wakefulness and heightened arousal rather than sleep. The patient may fall asleep easily outside the bedroom (i.e., when watching television or reading in the living room) but feel wide awake in bed. It is important to note that once this conditioning process has occurred, the patient's insomnia may persist long after the original psychosocial or medical stressor has been resolved. ****TABLE 1 Common Causes of Insomnia    Nonprescription drugs       Alcohol (promotes sleep onset, but tends to shorten total sleep time)       Caffeine       "Diet pills" (e.g., those including pseudoephedrine, phenylpropanolamine)       Nicotine    Prescription drugs       Beta-adrenergic blockers       Thyroid preparations       Corticosteroids       Selective serotonin reuptake inhibitors       Monoamine oxidase inhibitors       Methyldopa (Aldomet)       Phenytoin (Dilantin)       Methylphenidate (Ritalin)       Theophylline       Albuterol       Quinidine       Pemoline       Phenylephrine    Medical conditions       Primary sleep disorders (sleep apnea, periodic limb movement disorder,         nocturnal myoclonus,restless legs syndrome)       Pain from any source or cause       Drug or alcohol intoxication or withdrawal       Thyrotoxicosis       Dyspnea from any cause (CHF, COPD)       Menopause (hot flush)       Gastroesophageal reflux       Urinary incontinence (BPH)    Psychologic causes       Depression       Anxiety , Panic disorder       Life stressors       Bedtime worrying       Mania or hypomania    Environmental causes       Bedroom too hot or too cold       Noise       Eating, exercise, caffeine or alcohol use before       bedtime       Jet lag       Shift work       Daytime napping Treatment Management of chronic insomnia begins with attempts to identify and treat any underlying causes. There may be more than one cause of insomnia, but the causes may be difficult to identify. Drug therapy may be beneficial for short-term improvement, while behavioral intervention provides more sustained effects. Long-term use of many psychotropic or sedative-hypnotic drugs can cause adverse reactions and may actually impair sleep. Behavioral intervention combined with pharmacologic agents may be more effective than either approach alone. Psychologic and Behavioral Treatment of Insomnia Sleep diary Having the patient keep a sleep diary for two weeks may be helpful. Depending on the findings in the sleep diary, a discussion of sleep hygiene may be beneficial Cognitive Therapy. Cognitive therapy involves identifying dysfunctional beliefs and attitudes about sleep and replacing them with more adaptive substitutes. For example, patients who believe that sleeping eight hours per night is absolutely necessary to function during the day are asked to question the evidence and their own experience to see if this is true for them. Patients who are convinced that insomnia is destroying their ability to enjoy life are encouraged to develop more adaptive coping skills and to cease viewing themselves as victims. These attitudinal changes often help minimize the anticipatory anxiety and arousal that interfere with sleep. Stimulus Control Therapy The purpose of stimulus control therapy is to re-establish the connection between the bed and sleep by prohibiting the patient from engaging in non-sleep activities while in bed. This treatment is easily administered by the family physician and has demonstrated efficacy. 1. Go to bed only when sleepy. 2. Do not use the bed for any activities other than sleep (or sex). Do not read, watch television or eat. 3. If you don't fall asleep in about 20 minutes, leave the bedroom. Return to bed when you are sleepy. 4. Repeat step 3 as many times as needed until sleep occurs within 20 minutes of returning to bed. 5. Get up at the same time each day regardless of how much you slept. 6. Do not nap during the day or sleep in locations other than bed. Sleep Restriction Therapy Poor sleepers often increase their time in bed in an effort to provide more opportunity for sleep, a strategy that is more likely to result in fragmented and poor-quality sleep. Sleep restriction therapy consists of curtailing the amount of time spent in bed to increase the percentage of time spent asleep. This improves the patient's sleep efficiency (time asleep/time in bed). For example, a person who reports staying in bed for eight hours but sleeping an average of five hours per night would initially be told to decrease the time spent in bed to five hours. The allowable time in bed per night is increased 15 to 30 minutes as sleep efficiency improves. Adjustments are made over a period of weeks until an optimal sleep duration is achieved. To minimize daytime sleepiness, time in bed should not be reduced to less than five hours per night. Sleep restriction therapy is modified in older adults by allowing a short afternoon nap. Sleep Hygiene Education Sleep hygiene education consists of a set of instructions regarding environment and lifestyle factors that affect sleep. Sleep hygiene is not effective as the sole intervention for insomnia but is recommended as an adjunct to other forms of therapy. 1. Decrease or eliminate the use of caffeine, especially after noon. 2. Do not use tobacco or alcohol near bedtime. 3. Avoid heavy meals close to bedtime. However, a light snack at bedtime may promote sleep. 4. Regular exercise in the late afternoon may deepen sleep. Vigorous exercise within three to   four hours of bedtime may interfere with sleep. 5. Establish a regular schedule for going to bed and getting up. Avoid daytime naps. 6. Keep the bedroom at a comfortable temperature and minimize light and noise. 7. Do not use the bed as a place to worry (especially about not sleeping). If necessary, write   down your worries and concerns before you go to bed and place the list on your dresser to   examine the next morning. 8. Use the bedroom only for sleep (and sex). Don't read, watch television, eat or do other   activities in bed. 9. Get regular exposure to outdoor sunlight, especially in the late afternoon. Relaxation Therapy. Of several relaxation methods, none has been shown to be more efficacious than the others. Progressive muscle relaxation, autogenic training and electromyographic biofeedback seek to reduce somatic arousal (e.g., muscle tension), whereas attention-focusing procedures such as imagery training and meditation are intended to lower presleep cognitive arousal. Abdominal breathing may be used as a component of various relaxation techniques, or it may be used alone. Phototherapy Advanced sleep-phase syndrome may be corrected through exposure to bright light for two hours during the evening, which may shift the body's circadian timing mechanism and delay the onset of sleep until a typical bedtime. In contrast, delayed sleep-phase syndrome may be treated by exposure to bright light in the morning. Pharmacologic Treatment ・Benzodiazepine The primary indication for hypnotic medication is short-term management of insomnia--either as the sole treatment modality or as adjunctive therapy until the underlying problem is controlled. The most common medications used to promote sleep are benzodiazepine receptor agonists. Differences between the compounds' ability to induce and maintain sleep are based on rate of absorption and elimination. The most common side effects of these medications are anterograde amnesia and, for long-acting drugs, residual daytime drowsiness and vertigo, dysarthria, and ataxia and they often have additive effects when used in conjunction with other central nervous system depressants, such as alcohol. Currently an estimated 10 to 15 percent of patients who use hypnotic medications use them regularly for more than one year, although little safety or efficacy data are available to guide their use beyond two to three months. While selected patients may benefit from chronic use of these medications, there are no clear indications showing which patients might benefit from chronic therapy. In patients who need to be alert because of occupational or societal demands, short-acting medications are preferred. However, patients with insomnia and high levels of daytime anxiety may benefit more from long-acting medications. It is important to remember that, with age, the volume of distribution increases and the rate of metabolism slows for most of these medications. Hypnotic medications are contraindicated in pregnant women, patients with untreated obstructive sleep apnea, patients with a history of substance abuse and patients who might need to awaken and function during their normal sleep period. Finally, patients with hepatic, renal or pulmonary disease must be monitored more carefully than otherwise healthy patients with insomnia. ・Antidepressants It is very common for sedating antidepressants to be prescribed for insomnia, often in low dosages, but little scientific evidence supports the efficacy or safety of this approach in the treatment of most types of insomnia. When prescribed for patients with major depression, sedating antidepressants improve insomnia, and sleep symptoms often improve more quickly than other symptoms of depression. When administered concurrently with "alerting" antidepressants, low dosages of sedating antidepressants such as trazodone again improve insomnia. However, in nondepressed patients, the data to recommend use of antidepressants are minimal. Antidepressants have a range of adverse effects including anticholinergic effects, cardiac toxicity, orthostatic hypotension and sexual dysfunction (selective serotonin reuptake inhibitors [SSRIs]). Tricyclic antidepressants and SSRIs can exacerbate restless legs syndrome and periodic limb movement disorder in some patients.. ・Antihistamines. Few recent studies have assessed the efficacy of antihistamines in the treatment of insomnia, but older studies demonstrated subjective and objective improvements during short-term treatment. The long-term efficacy of antihistamines in the management of insomnia has not been demonstrated. Adverse effects associated with antihistamines include daytime sedation, cognitive impairment and anticholinergic effects. Tolerance and discontinuation effects have been noted. Finally, a variety of herbal preparations (e.g., valerian root, herbal teas), so-called nutritional substances (e.g., l-tryptophan) and over-the-counter drugs are promoted, especially in the lay press. In general, little scientific evidence supports the efficacy or safety of these products. ・Melatonin Melatonin is a hormone secreted by the pineal gland and is purported to have sleep-inducing properties. Although the effectiveness of melatonin remains controversial, it has received attention in the treatment of insomnia caused by circadian schedule changes (i.e., jet lag, shift work). In these circumstances, melatonin successfully hastens adaptation to the new circadian schedule. No systematic long-term studies of the use of melatonin have been reported. Its ingestion in pharmacologic dosages has the potential to induce undesirable side effects, such as sleep disruption, daytime fatigue, headache, dizziness and increased irritability. ****よく用いられる催眠薬    薬物      半減期(時間) 利点および欠点                 投与量*(mg)    ベンゾジアゼピン類    ハルシオン   1.5-3     入眠障害に有用;高用量では前向性健忘を誘発する 0.125-0.25    リスミー    10                               1-2    レンドルミン  6-9.5     緩徐に吸収;熟眠障害に有用            0.25-0.5    デパス     6       抗不安作用あり                  1-3    ワイパックス  10-20     中程度の長さの鎮静               1-4    ユーロジン   16-18     投与量の範囲ではほとんど残留効果がない     0-2    ベンザリン†  25-35     日中の若干の鎮静を許容できるなら頻回覚醒に有用 2.5-10    セルシン†   30-56     薬物およびその活性代謝産物の排出が遅いため蓄積する 2.5-10    ドラール    39       長期使用は推奨されない;早朝覚醒に有用なことがある 7.5-15    インスミン†  40-100    日中の若干の鎮静を許容できるなら頻回覚醒に有用  15-30    メンドン†    55-70     不安を伴う不眠に有用               7.5-22.5    抗うつ薬‡    アミトリプチリン 16      就寝時に全量を用いるとうつ病および早朝覚醒の患者の                    不眠が改善されることがある;抗コリン作用が強い  50-100   その他    抱水クロラール  4-10     中程度の長さの鎮静;消化管作用および残留効果   500-1000    一般用催眠薬     ジフェンヒドラミン§,大部分に軽度の鎮静がみられるが,鎮静作用は3-4日の使用後には                消失する;強い抗コリン作用(口内乾燥,視力障害,尿閉,便秘)は,                     高齢者および緑内障,良性前立腺肥大,痴呆の患者で特に問題となる.     *高齢患者に対する初回量は,しばしば最小量の1/2で十分である。     †加齢に伴って半減期が延長するため,高齢者への投薬は避けるべきである。     ‡うつ病がなければ抗うつ薬を用いるべきではない。 §抗コリン作用が強いため,高齢者への投薬は      避けるべきである。 Reference -Insomnia: Assessment and Management in Primary Care http://home.org/afp/990600ap/3029.html -Chronic Insomnia: A Practical Review Am Fam Physician 1999;60:1431-42 -The diagnosis and management of insomnia in clinical practice: a practical evidence-based approach CMAJ 2000;162(2):216-20 -Behavioral Medicine In Primary Care A Practical Guide

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