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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