Approach to insomnia

L P W Chiu 趙伯宏

HK Pract 2003;25:435-445

Summary

Insomnia is defined in the DSM-IV in very strict terms. The predominant complaint is difficulty initiating or maintaining sleep, or non-restorative sleep, for at least one month. The sleep disturbance (or associated daytime fatigue) must also cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Community surveys found that 10% to 30% of adults complained of insomnia. Common causes of transient insomnias include environmental sleep disorder, adjustment sleep disorder, drug-induced sleep disorder, and circadian rhythm sleep disorder. Common causes of chronic insomnias include sleep disorders associated with medical/psychiatric disorders, primary insomnia, and sleep apnoea syndrome. Assessment of insomnia aims at answering a few questions: (1) What is the nature of the insomnia? (2) What is the severity? (3) What are its causes? Management includes excluding causes of transient insomnias and organic causes (drugs, physical diseases, sleep apnoea), diagnosing psychiatric disorders, treating with appropriate psychiatric drugs, and educating patients about sleep hygiene.

摘要

失眠的定義是：(1)病人持續一個月有困難入睡或維持睡眠，或睡醒後仍覺疲倦。(2)這睡眠問題導致苦惱，或影響日常生活。社區調查發現百分之十至百分之三十的成人患有失眠。短暫失眠的常見原因包括：環境性睡眠問題、適應性睡眠問題、藥物引起的睡眠問題、及日夜節奏睡眠問題。長期失眠的常見原因包括：因身體或精神病導致的睡眠問題，原發性睡眠問題，及睡眠窒息症。面對失眠病人醫生要了解三方面：(1) 失眠的性質；(2)失眠的嚴重性；(3)失眠的原因。失眠的處理包括：排除短暫失眠的原因，排除生理因素（藥物，身體疾病，睡眠窒息症），教導病人衛生睡眠習慣，診斷精神病，用適當精神科藥物治療。

Introduction

Insomnia is a common complaint seen in family/general practice. A significant proportion of a family physician's work is to manage patients with insomnia. This paper reviews the definition, epidemiology, causes, assessment, and management of insomnia.

Definition

Studies showed that insomnia secondary to a medical or psychiatric disorder was found in about 85% of cases.^2-4 In the remaining 15%, no cause could be found. These latter patients are said to suffer from "primary insomnia". Primary insomnia is defined in the DSM-IV by the 2 criteria above, plus the following 3 additional criteria: (1) The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or a parasomnia. (2) The disturbance does not occur exclusively during the course of another mental disorder (e.g. major depressive disorder, generalised anxiety disorder, a delirium). (3) The disturbance is not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition.¹

Epidemiology

There is a wide range of variation in estimates of the prevalence of insomnia, depending on the definition and the population studied. Community surveys found that 10% to 30% of the adult population complained of insomnia.^2-4

The consequences of insomnia can be gauged from the following studies: (1) A prospective study in the US found that those who habitually slept 7 to 8 hours a day had the lowest death rate. There was a 10-fold elevation in death rate for those who habitually slept only 4 hours or less a day and 10 hours or more a day.³ (2) A multi-centre community survey found that self-reported insomnias were associated with increased medical illnesses in the 3 years following.⁵ (3) In the UK, a prospective study of non-depressed citizens found that subjective complaints of sleep disturbance were a predictor of future depression.⁶

Causes

Common causes of insomnia are listed in the International Classification of Sleep Disorders (ICSD),⁷ which is simplified in Table 1.

ICSD first divides sleep disorders into primary sleep disorders and sleep disorders secondary to medical/psychiatric disorders. Primary sleep disorders are again divided into dyssomnias and parasomnias. Dyssomnias are characterised by disturbance in the amount, quality, or timing of sleep. Dyssomnias include insomnias and hypersomnias. Dyssomnias are further divided into 3 groups: (1) Intrinsic sleep disorders, (2) Extrinsic sleep disorders and (3) Circadian rhythm sleep disorders. Parasomnias are characterised by abnormal behaviours or physiological events associated with sleep, e.g. sleepwalking, sleep enuresis, sleep terrors, etc.

In clinical practice, it is useful to divide insomnias into transient insomnias (lasting less than 2 weeks) and chronic insomnias (lasting more than 2 weeks). Common causes of transient insomnias include environmental sleep disorder (e.g. hot or noisy environment), adjustment sleep disorder (e.g. a reaction to transient stress), drug-induced sleep disorder (e.g. amphetamine-type of appetite suppressants), and circadian rhythm sleep disorders (e.g. jet lag). Common causes of chronic insomnias include sleep disorders associated with medical/psychiatric disorders, primary insomnia, and the sleep apnoea syndrome.

ICSD defines the following 4 distinct types of primary insomnia⁷:

1. Psychophysiological insomnia - This occurs when a patient has developed a conditioned arousal associated with attempts to sleep. It usually starts as insomnia in response to transient stress. Unfortunately, the bed has become a conditioned stimulus that perpetuates insomnia, so that even when the transient stress has disappeared, the patient has conditioned insomnia every time he/she goes to bed.
2. Sleep state misperception - This is diagnosed when a patient complains of difficulty initiating or maintaining sleep but no objective evidence of sleep disruption is found (e.g. from bed-partner's report or from polysomnography study). Sleep state misperception can occur during periods of stress and can result from latent depressive or anxiety (especially obsessional) disorders.
3. Idiopathic insomnia - This typically starts early in life, sometimes at birth, and continues throughout life. As the name implies, its cause is unknown. Speculated causes include neurochemical imbalance in the brainstem reticular formation, impaired regulation of brainstem sleep generators (e.g. raphe nuclei, locus coeruleus), or basal forebrain dysfunction.
4. Inadequate sleep hygiene - This is caused by the performance of daily living activities that are inconsistent with the maintenance of good quality sleep. These activities include getting up very late and long daytime naps.

Assessment

Assessment of insomnia needs to answer 3 questions: (1) What is the nature of the insomnia? (2) What is the severity? (3) What are the causes of the insomnia?

To clarify the nature of the insomnia, the doctor should ask whether there are difficulties in falling asleep, maintaining sleep, or awakening early. Patient's bedtime routine, sleep setting, timing of sleep and wakefulness throughout the 24-hour day should also be assessed.

To assess the severity of the insomnia, the doctor should look for excessive daytime sleepiness and fatigue. The patient should be asked whether the sleep disturbance (or associated daytime fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. In particular, the patient's beliefs about sleep and worries about consequences of insomnia should be assessed.

To find out the causes of the insomnia, the doctor can ask about use of all prescription and non-prescription medications and drinks (including coffee, tea, alcohol). One should also take medical, psychiatric, and social histories (including work, relationship, financial, and accommodation problems). Physical and mental-state examinations and necessary laboratory investigations should be performed to find out whether there are medical and psychiatric disorders causing secondary insomnia.

It is very important to ask the patient's bed partner about patient's sleep patterns, abnormal behaviours during sleep (e.g. heavy snoring), and excessive daytime sleepiness because the patient may not be able to give an accurate account of these aspects.

A useful tool to check patient's sleep problem is to ask the patient to keep a sleep diary over a period of about 2 weeks. The patient should record in the diary every time he/she goes to bed, gets to sleep (patient may need to ask the bed-partner), wakes up, gets out of bed and daytime naps. Quality of sleep, daily activities and stress, medication used and drinks are also recorded. An ingenious method to screen for sleep apnoea is a tape recording of respiratory sound during sleep.⁸ If sleep apnoea or parasomnias are suspected, the patient should be referred for polysomnography study.^9,10

Management

The management of insomnia can be depicted by the algorithm in Figure 1.

According to DSM-IV, insomnia can be diagnosed only if the sleep disturbance (or associated daytime fatigue) causes clinically significant distress or functional impairment. Hence if the patient is not tired during the day, he/she can be reassured that his/her sleep need is already met and he/she should be encouraged to regard his/her additional awake time as a bonus.

If the onset of insomnia is only recent, then jet lag, change of sleep environment (e.g. a new bed) or sleep habits (e.g. change in work shift) should be considered.⁷ The patient should be reassured that his/her insomnia is only a transient problem. If the patient is very distressed, then it is appropriate to prescribe a few days of hypnotics.

Patients taking high doses of psychostimulants (e.g. amphetamine-type of appetite suppressants) for a long time not only suffer from insomnia,¹¹ but also have a high risk of developing schizophreniform or paranoid psychosis.¹² Patients with physical causes of insomnia like pain or dyspnoea should be treated accordingly.¹³

A history of poor sleep, excessive daytime sleepiness and intermittent heavy snoring, particularly in overweight patients over the age of 40 years, is suggestive of sleep apnoea. Such patients should be referred for polysomno-graphy study.^9,10 If sleep apnoea is confirmed, then it is important not to prescribe sedative medications because these drugs may worsen the sleep apnoea.¹⁴ The most effective treatment of sleep apnoea is positive airway pressure;¹⁵ however non-sedating tricyclic anti-depressant drugs may decrease the severity of apnoea by reducing REM-sleep, the stage of sleep in which apnoea is usually more frequent.¹⁶

It is very important that before any drug for insomnia is prescribed, the patient is educated about sleep hygiene, as shown in Table 2.¹⁷ Even if a patient is prescribed a drug for insomnia, he/she should continue with good sleep hygiene. Otherwise, the patient may need higher and higher dose of the drug to induce sleep.¹⁷ This is because after taking drugs for insomnia, the patient may get up very late in the morning, and not easily feel tired the next night. He/She will then step up the dose of the drug to go into sleep that night and get up even later the next morning, resulting in a vicious cycle. This problem is illustrated in the following case:

Case 1

Mrs A was a 40 years old housewife presenting with insomnia despite 4 tablets of flunitrazepam 1mg, which she had been taking every night for 3 years! History-taking revealed that she used to getting up after 2 p.m. every day! Mrs A was educated about sleep hygiene. Then a behavioural therapy programme was designed for her - she set a loud alarm clock to get up 10 minutes earlier each day, and rewarded herself by watching her favourite movies. After about 3 months, Mrs A could get up before 8 a.m. Then her flunitrazepam was reduced by 1/2mg every 2 weeks. Six months later, she needed to take only 1mg of flunitrazepam twice per week to sleep.

The diagnosis of various psychiatric syndromes has been discussed previously by the author in an earlier paper.¹⁸ If there are signs of organic brain syndrome, then delirium and dementia have to be excluded. As delirium may be caused by cerebral or systemic disease and drug intoxication or withdrawal, treatment of the underlying cause will remove the insomnia. On the other hand, insomnia in dementia patients may pose a long-term problem. Environmental modification (e.g. making the environment safe, increased lighting late in the day, pleasurable distractions and activities, increased attention from care-givers) can be tried first.¹⁹ In the past, hypnotics and antipsychotic medications were widely used to treat insomnia in dementia patients, but these would impair patients' cognitive function further.²⁰ The anti-cholinergic side-effects of tricyclic antidepressants may also impair patients' cognitive function as well as cause urinary retention.²¹ Recent studies show that cholineste-rase inhibitors (e.g. tacrine, donepezil, rivastigmine, galanthamine) can improve the sleep of dementia patients.^22-24 If dementia patients still have insomnia despite cholinesterase inhibitors, then the non-tricyclic sedative antidepressants (e.g. mianserin, trazodone, mirtazapine) may be tried. These non-tricyclic anti-depressants can also treat depressive pseudodementia.²⁵

If the patient has delusions, hallucinations, or manic symptoms, then schizophreniform psychosis, paranoid psychosis, or mania has to be considered. His/Her insomnia cannot be treated by hypnotics alone and must be treated by antipsychotic and/or mood-stabilising drugs.²⁶

Primary care doctors often encounter patients with a mixture of fluctuating anxiety and depressive symptoms.²⁷ The management of these patients have been discussed before.²⁸ Presence of the following depressive features suggest that the patient should be treated with antidepressants rather than anxiolytics: appearing tearful, loss of interest in activities, significant weight loss, hypersomnia, psychomotor retardation, fatigue, feelings of hopelessness, poor concentration, suicidal ideation.¹ This is because anxiolytics may worsen these depressive features.^27-29 On the other hand, sedative antidepressants are as effective as anxiolytics in treating patients with anxiety symptoms.^30-31 Doctors should beware that patients with significant anxiety symptoms may not be able to tolerate the side-effects of tricyclic anti-depressants.³² Moreover, tricyclic antidepressants are lethal in overdose.³² Therefore, patients with a mixture of both depressive and anxiety symptoms are best treated with the non-tricyclic sedative antidepressants (e.g. mianserin, trazodone, mirtazapine). Unfortunately, these newer antidepressants are considerably more expensive than tricyclic antidepressants and anxiolytics.

In treating depressive patients with selective serotonin reuptake inhibitors (SSRI), doctors should beware that SSRI may worsen insomnia.³³ Hence depressive patients with insomnia should either be treated with a combination of SSRI and anxiolytics, or be treated with sedative antidepressants.³³ Doctors should not forget that both depressed patients and anxious patients need psychological treatments in addition to pharmacotherapy.³⁴ Impaired concentration is a diagnostic symptom of both major depressive disorder and dysthymic disorder in DSM-IV.¹ If patients with depressive disorder are prescribed hypnotics, the additional impairment in concentration caused by hypnotics may cause them to forget to pay for goods taken away from shops. They may innocently be arrested for theft, as illustrated in the following case:

Case 2

Mr B was a 46-year-old manager who was arrested for stealing a cheap stapler from a supermarket. History-taking revealed that his wife had died of renal disease one month ago. During this bereavement period, Mr B's insomnia was so severe that he could not sleep well despite 3 tablets of zolpidem 10mg every night! On the day of arrest, he wanted to buy a stapler from the supermarket before going to work, and forgot to pay for it. Mental examination of Mr B revealed that he was severely depressed with overt tears, psychomotor retardation, loss of interest in everything, guilt feeling, and suicidal idea. Mr B was diagnosed as suffering from major depressive disorder. His zolpidem was gradually tailed off and replaced with mirtazapine 30mg nocte. His insomnia disappeared instantaneously and his depressive symptoms slowly subsided in the following 4 weeks. A psychiatric report testifying Mr B's major depressive disorder was submitted to the court. Mr B was subsequently acquitted.

Patients with signs of anxiety disorder should first be treated with less potent long-acting anxiolytic drugs (e.g. diazepam, chlordiazepoxide) rather than potent short-acting sedatives (e.g. alprazolam, lorazepam) or hypnotics (e.g. midazolam, triazolam) to prevent dependence and withdrawal symptoms,^35-37 as illustrated in the following case:

Case 3

Mr C was a 24-year-old salesman admitted into a private hospital for sudden grand mal seizure in the morning. Physical examination, blood tests, computerised tomography of the brain and electroencephalography all yielded normal results. History-taking revealed that he had been taking 4 tablets of triazolam 0.25mg every night for the past 2 years! On the night before admission to hospital, he drank 4 glasses of wine with friends before sleep without taking triazolam. Mr C was diagnosed to have epilepsy due to alcohol and triazolam with-drawal. He was advised to abstain from alcohol and his triazolam was replaced with diazepam 20mg nocte. The dosage of diazepam was decreased by 5mg every 2 weeks. Meanwhile, Mr C was educated about sleep hygiene and was taught relaxation exercise. Four months later, Mr C needed to take only diazepam 5mg twice per week to sleep.

If the patient has received sedatives or hypnotics for a long time, it is highly desirable to attempt gradual withdrawal to prevent dependence. The principle of withdrawal is to substitute the short-acting sedatives or hypnotics with an equivalent dosage of long-acting diazepam, and then gradually decrease the dosage of diazepam by 5mg every 2 weeks.³⁸

Finally, patients who develop transient insomnia in response to temporary stressful events may be prescribed intermittent zolpidem or zopiclone for a short period of time. These non-benzodiazepine hypnotics are superior to benzodiazepine hypnotics in that there is no rebound REM-sleep on withdrawal.³⁹ However, prolonged use of any hypnotic, including non-benzodiazepine hypnotics, is not recommended.

Conclusion

Treatment of intractable insomnia can be a difficult challenge to any doctor, especially if it does not respond to low doses of hypnotics. However, when a doctor has successfully alleviated his/her patient's tormenting insomnia, the gratitude from his patient can be a great reward.

Key messages

1. If a patient is not tired during the day, his/her insomnia need not be treated. He/She should be encouraged to occupy extra awake time fruitfully.
2. Sedative medications may worsen sleep apnoea while non-sedating tricyclic antidepressant drugs may decrease apnoea severity by reducing REM-sleep, the stage of sleep in which apnoea frequently occurs.
3. Even if a patient is prescribed a drug for his/her insomnia, he/she should continue with sleep hygiene. Otherwise, he/she may need higher and higher dose of drug to sleep.
4. Recent studies show that cholinesterase inhibitors (e.g. tacrine, donepezil, rivastigmine, galanthamine) can improve the sleep of dementia patients.
5. The insomnia of psychotic and manic patients cannot be treated by hypnotics alone and must be treated by antipsychotic and/or mood-stabilising drugs.
6. If patients with depressive disorder are prescribed hypnotics, the additional impairment in concentration caused by hypnotics may cause them to forget to pay for goods taken away from shops.
7. Patients with signs of anxiety disorder should first be treated with less potent long-acting anxiolytic drugs rather than potent short-acting sedatives or hypnotics to prevent dependence and withdrawal epilepsy.