Key points for prescribing:

  • Sleeping pills can be effective, but chronic use should be avoided
  • Always recommend sleep hygiene
  • Consider a combined behavioural and hypnotic approach
  • Most hypnotic side effects are dose-related
  • Use the lowest effective dose for the shortest amount of time

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Introduction
Types of insomnia 
Prevalence
Pathophysiology
A complex clinical picture
Consequences
Causes of insomnia
Assessment and diagnosis
Management
Cognitive and behavioural treatment of insomnia 
Medication
References

 

Introduction

Sleeplessness, or insomnia, is a disorder in which a person senses having inadequate quantity or quality of sleep and is the most common sleep complaint reported to GPs. With the modern lifestyle, and the 24/7 stress system requiring continuous connection and reachability, the incidence of insomnia is increasing in all segments of the population. 

Insomnia can be either acute – lasting a few nights – or chronic, lasting many months or years. It can be isolated, but it is often a symptom of other medical or psychiatric conditions. The disorder is often associated with functional impairment during the daytime, such as reduced attention, inappropriate vigilance, dysphoric mood and fatigue. Driver sleepiness, secondary to sleep loss, accounts for about 20% of serious car crashes, independent of those caused by alcohol.1

Several studies have shown that the adverse effect of insomnia on quality of life is similar to that of depression.

Insomnia has been shown to be both underreported and undertreated. In an earlier US poll, 70% of patients reported that they never discussed the problem with their GP; 30% mentioned it only in passing, and only 6% booked a consultation about it.2

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) the term “primary insomnia” has been replaced with the diagnosis of “insomnia disorder”, thus avoiding the primary/secondary designation when the disorder accompanies other conditions and offering an improved framework for insomnia care and research.

Types of insomnia

Insomnia can be differentiated in two ways: by aetiology and by duration

Aetiology

  • “Primary insomnia”: does not occur as a result of a medical or psychiatric disorder.  
  • Comorbid (secondary) insomnia: occurs in association with another medical, psychiatric or sleep disorder.

There are four cardinal symptoms or types of insomnia disorder:  

  • Difficulties in falling asleep (initiating sleep, DIS)  
  • Difficulties in maintaining sleep (DMS)  
  • Early morning awakening (EMA)  
  • Non-restorative sleep (NRS), with subjects experiencing one or many of these symptoms. 

In a survey of a few thousand US adults, Walsh et al observed that the most common problem was difficulty in maintaining sleep (61%), followed by EMA (52%), while DIS (37%) and NRS (25%) were less marked. Furthermore, it was reported that all these symptoms were related to a wide range of co-morbid mental and physical conditions, with DMS having the strongest associations.3

Duration  

  • Transient insomnia: Simple episode of insomnia lasting less than two weeks  
  • Intermittent insomnia: Repetitive episodes of transient insomnia  
  • Chronic insomnia: Continuous problem lasting for more than one month. In current practice, insomnia is considered as chronic if it occurs at least three nights per week for at least three months.

While patients with persistent insomnia every night for years are rare, most complain of difficulty sleeping for a few nights, followed by a few nights of better sleep before the problem returns – known as intermittent chronic insomnia.

Prevalence

Depending on the criteria and groups of patient studied, insomnia is reported to occur within a given year in 20% to 40% of the general population, with about 10-15% of adults complaining of chronic insomnia (>12 months duration)4 and women more afflicted than men. 

Prevalence of insomnia increases with age. However, it is not uncommon for elderly subjects with sleeping problems to report less clinically significant impairment, resulting in a low prevalence of insomnia diagnoses among older people. Ohayon and Reynolds suggest that current diagnostic criteria for insomnia might be inadequate for geriatric populations.5

Pathophysiology

Does insomnia represent a “hyperarousal” condition of the autonomic nervous system (ANS) and central nervous system (CNS) as well as an emotional level? There is certainly evidence of sympathetic hyperarousal, raised levels of circulating catecholamines, increased basal metabolic rate and body temperature, altered heart rate variability/reduced respiratory sinus arrhythmia (RSA) and elevated beta EEG frequency. 

This concept of hyperarousal is gaining more attention. It offers new therapeutic approaches beyond the standard treatment with hypnotics (with their associated risks of intolerance, abuse and dependence, rebound effect, memory impairment and nocturnal falls in the elderly).

A complex clinical picture

Chronic insomnia can develop into a complex picture with a cluster of symptoms influencing each other (see Figure 1). 

Tackling insomnia in everday practice: Part 1 - Fig 1

Sleep loss affects the response to stress, which in return has a negative impact on sleep. Insomnia also gives rise to anxiety and depression with somatisation (the ANS governs gastrointestinal disturbances, palpitations etc) and muscle tension, for example, which in turn worsens sleep. The patient often ends up using polypharmacy to address all these conditions.

Consequences

Economic consequences: Insomnia has a significant economic impact resulting in hugely increased health care costs and reduced productivity, including indirect costs such as absenteeism, injuries, increased alcohol consumption etc. The consequences of untreated insomnia greatly outweigh the costs incurred by adequate treatment.6

Cognitive and health consequences: According to the DSM-5, six areas may be impacted by insomnia during the daytime: energy, concentration, relationships, ability to stay awake (risk of accidents), mood, and ability to work effectively. In addition, by preventing restorative sleep (hence maintaining a high level of stress agents), chronic insomnia has also been shown to be a risk factor for cardiovascular and depressive disease, as well as metabolic disorders (diabetes, triglycerides etc.).

Causes of insomnia

There are many factors that can result in insomnia, including an irregular lifestyle, stress, changes in the environment and work schedules, disease, pain and tension, anxiety, depression, alcohol, caffeine, medicine, recreational drugs and of course poor sleep habits.

Psychophysiological insomnia 

This common problem is conditioned arousal to the physical sleep environment comprising a paradoxical behaviour: the subject has difficulty getting to sleep at night but can fall asleep unintentionally and can sleep better away from the bedroom. He/she ruminates and worries in bed, becoming more and more frustrated in trying to sleep. The consequences include daytime tiredness, performance anxiety and muscle tension.

Comorbid insomnia (associated with other disorders) 

There are five major diagnostic categories (see Figure 2)  

  • Medical  
  • Psychiatric  
  • Pharmacological  
  • Behavioural  
  • Primary sleep disorders

Tackling insomnia in everday practice: Part 1 - Fig 2

Medical disorders 

Numerous medical disorders are associated with insomnia, including hyperthyroidism, arthritic conditions, chronic renal disease, chronic lung disease, heart failure, reflux oesophagitis, hepatic disease, sleep-related asthma and myalgic encephalopathy (ME). 

Common co-morbid neurological disorders include multiple sclerosis, cerebral degenerative disorders, dementia, Parkinsonism, sleep-related headaches, and electrical status epilepticus in sleep (ESES). Pain is also a prominent factor; 50-70% of patients with chronic pain have impaired sleep.

Psychiatric disorders 

Most patients with psychiatric disorder develop insomnia at some point, and when prolonged (>1 year) insomnia may be an early warning of developing a psychiatric disorder (40% of patients with chronic insomnia have one). 

Mood disorders include depression, anxiety disorders, panic disorders, schizophrenia, personality disorders and alcoholism. Obsessive-compulsive personality disorder is also a common cause of insomnia. 

The severity of insomnia co-varies with the severity of the underlying disorder; the incidence of major depression, anxiety disorder, alcohol and drug abuse/ dependency is much higher if there is a prior history of insomnia. 

Early morning waking could indicate depression, whereas trouble falling or staying asleep is one of the criteria for anxiety disorder. 

Pharmacological factors 

Insomnia may be caused by withdrawal from many different drugs, including:  

  • Alcohol, CNS stimulants, nicotine, beta blockers, bronchodilators, corticosteroids, decongestants   
  • Stimulating antidepressants (imipramine, desipramine, fluoxetine, paroxetine, venlafaxine, reboxetine, bupropion)  
  • Thyroid hormones, phenytoin

Behavioural causes

These include poor sleep hygiene, an irregular sleep schedule, excessive napping, caffeine, exercise and mental stimulation close to bedtime or negative sleep associations (reading, TV etc).

Primary sleep disorders

Among the primary sleep disorders which can develop insomnia symptoms are periodic limb movement disorders (PLMD), restless leg syndrome (RLS) and in some subjects obstructive sleep apnoea (OSA). 

Circadian rhythm disorders are a major cause of insomnia: “eveningness” – delayed sleep phase syndrome observed in young people, “morningness” – advanced sleep phase syndrome, often observed in the elderly; shift work and jet lag (although this seldom yields to chronic insomnia).

Assessment and diagnosis

A comprehensive medical history is essential and is the most important part of the diagnosis. It aims to determine personal health and recognise present and past causal factors, predispositions and other possible contributory health conditions. 

It is also important to evaluate any childhood insomnia disorder. Adverse childhood experiences are associated with adult insomnia in a dose-related fashion. 

Sleep inventories and other questionnaires, including the Insomnia Severity Scale (ISS: See figure 2), as well as various sleepiness scales, should provide information about sleep-wake habits and patterns. 

The patient should be given a sleep logbook, in which they can record key factors, such as bedtime, wake up time, sleep quality and other information related to the wake-sleep conditions which may be of relevance (many examples can be found on the internet, e.g. http://www.railroadersleep.org/). 

A sleep log should be kept simple – even at the expense of losing some information. It should be quick and easy to fill in and should be kept for at least two weeks to include two weekends. 

While a sleep log reflects a subjective view of the sleep-wake pattern, it is often recommended to complement it with an objective measurement such as actigraphy (a small instrument similar to a wrist-watch that continuously measures physical activity). A sleep-wake pattern is obtained by means of an algorithm and can be compared to the sleep log, with which it should be used simultaneously. 

Blood tests should be performed to rule out any underlying medical condition, such as thyroid problems or other co-morbidities, which can disrupt sleep. 

Overnight sleep studies should be performed only when it is necessary to gather more information about night-time sleep which may contribute to insomnia, such as co-morbidity, abnormal movements or behaviour disorders. 

It is essential to identify the type of insomnia (DIS, DMS etc.), recognise any co-morbidity and rule out other conditions which may look like insomnia (e.g. narcolepsy with its paradoxical daytime sleepiness and difficulties sleeping at night).

Management 

The initial goal of management is to recognise and address any underlying cause:  

  • Any health condition, pain or disease  
  • Consistent irregularities in the sleep-wake (circadian) pattern, e.g. shift work or social jet lag  
  • Work, family, social situation, stress, conflicts  
  • Muscle tension  
  • Depression, anxiety  
  • Sleeping pill, other medication
  • Impaired sleep hygiene

In order to be effective, insomnia treatment should ideally be addressed on three levels, namely environmental, behavioural/relaxing and sleep aids (prescription and non-prescription/OTC medication and other means). 

The initial step in managing insomnia management is to identify and address any underlying cause: 

  • Any health condition, pain or disease 
  • Consistent irregularities in the sleep-wake (circadian) pattern, such as shift work or social jet lag 
  • Work, family, social situation, stress, conflicts 
  • Muscle tension 
  • Depression, anxiety 
  • Medication (for sleep disturbance and/or other conditions)
In order to be effective, insomnia treatment should typically be addressed on three levels, namely environmental, behavioural/relaxing and sleep aids (prescription and non-prescription/OTC medication and other means). Environmental approaches Patients should be advised: 
  • To avoid using a smartphone or tablet in bed. Their light frequency spectrum can have a negative impact on the release of melatonin, an essential hormone for sleep 
  • Not to use a computer after going to bed or try to read emails whose content may lead to worries 
  • To avoid watching television or movies after retiring or being exposed to any situation which may increase alertness and turn off as many electronic devices as possible 
  • To adjust the room and bed temperature. Although during wakefulness body temperature remains constant (through thermoregulatory mechanisms such as sweating, vasoconstriction or vasodilatation which adjust blood flow to the skin), during REM sleep, thermoregulation is minimal and body temperature falls to its lowest point or adjusts to the environment. The body cannot compensate for the ambient temperature changes and hence such changes can trigger awakening. 
  • Check that the room is quiet and quite dark and that the bed/pillows are comfortable. 
  • Avoid clocks in the bedroom. 

Cognitive and behavioural treatment of insomnia

Relaxation training for the mind and the body aims to reduce muscular and mental tension and avoid intrusive thoughts that may impede sleep. This may be: 
  • Cognitive: imagery (divert attention from problems and focus on interesting though trivial “pictures” based on a recent film seen or book read…), meditation, music… 
  • Somatic: breathing exercises, progressive muscular relaxation, autogenic training (simple relaxation and body awareness exercises aiming to reduce the body’s stress) etc. 
  • Listening to appropriate music or meditation CDs, together with various biofeedback systems can also be useful. 
Sleep restriction therapy: the amount of time spent in bed is limited to the actual amount of time spent asleep (as identified for example by the sleep log). This creates a mild and controlled sleep deprivation. As sleep improves, sleep time is increased progressively. This is a very efficient method but it needs to be used carefully. Restriction has to be adjusted in order to be effective, but it should be gradual or it will increase daytime somnolence, impaired vigilance with the risk of injuries and if extreme can trigger mental disorders (hallucinations etc.)
 
Stimulus control therapy aims to associate the bedroom with sleep and establish a solid sleep-wake pattern. 
 
Cognitive therapy: This should address any misconceptions about the causes of insomnia, unrealistic sleep expectations, performance anxiety etc.
 
Sleep hygiene includes the following strategies: 
  • Establishing healthy sleep habits 
  • Maintaining a very regular sleep schedule 
  • Cutting down time in bed 
  • Avoiding napping unintentionally – especially in the evening, e.g. while watching TV 
  • Exercising, ideally in the middle of the day, but no later than four hours before bedtime 
  • Avoiding alcohol, caffeine, nicotine and other stimulants close to bedtime – preferably no later than 4 hours prior going to bed 
  • Maintaining a healthy diet and avoid late and/or heavy meals 
  • Avoiding spicy foods at bedtime, which can lead to sweating 
  • Maintaining an adequate sleeping environment (temperature, noise, light) 
  • Unwinding before going to bed – no emails or other activities risking an increase in alertness. 
It is counterproductive to flood the patient with all sleep hygiene rules at once. It is essential to be aware that no sleep hygiene rule works for all insomniacs, so let the patient explore which works for him/her. The sleep log is designed for just this process. It is worth remembering that behavioural and cognitive therapies take time to work.  

Medication 

There are four types of medications commonly used for insomnia: 
  • Hypnotics (benzodiazepine and non-benzodiazepine, melatonin receptor agonists etc) 
  • Sedative antidepressants 
  • Antihistamines – neuroleptics 
  • OTC medications
Hypnotics
Benzodiazepines (e.g. loprazolam, lormetazepam, nitrazepam, temazepam) reduce anxiety and promote calmness, relaxation and sleep, but they can lead to dependency. They should, therefore, be used cautiously for a limited period, preferably selecting short-acting products such as temazepam. 
 
However, for the short-term management of insomnia, it is better to use the so-called Z-medicines, similar to benzodiazepines but short acting, such as zolpidem, zopiclone and zaleplon. NICE recommends against switching to an alternative Z drug if treatment with one is ineffective.
Tackling insomnia in everday practice: Part 2(1)
Women use more hypnotics than men, and this difference increases with age. Sedative polypharmacy is often found especially among older people. Barbiturates are not common. 
 
As much as possible it is best to avoid benzodiazepines, which can lead to addiction. Since they have a long half-life they affect daytime functioning and can result in sedation, falls, or cognitive/psychomotor impairment). They also affect sleep architecture. 
 
The speed of elimination of a benzodiazepine is obviously important in determining the duration of its effects. The box below shows the half-life of four of the most common benzodiazepines.

Melatonin 
Melatonin is a naturally occurring hormone that helps regulate the circadian rhythm. Melatonin and its agonists have been shown to be effective in treating sleeplessness in elderly people.
 
Circadin is slow-release melatonin (2mg)and can be prescribed for people older than 55 years and for up to 13 weeks. It often proves efficient in both improving sleep quality and circadian rhythms. It should be avoided if there is a history of liver impairment and used with caution in those with a kidney disorder. There are some minor side effects such as constipation and headache. 
 
Another product is Agomelatin (melatonin receptor agonist and t-HT2 antagonist); however, this is only licensed in the UK specifically for major depressive episodes.
 
Sedative antidepressants
Doxepin, mirtazapine, trazodone and trimipramine promote sleep, probably through resynchronisation of the circadian rhythm. (Trazodone 50 mg/7 days has improved sleep but impaired memory and driving.) 
 
Mirtazapine, a potent antidepressant, is often very effective in maintaining sleep (15-30 mg at bedtime). It has no sexual side-effects but increases appetite. 
 
Doxepin (a tricyclic antidepressant), is efficient in the treatment of insomnia characterised by difficulties in maintaining sleep (3-6 mg). Rebound insomnia is not an issue. 
 
It should be noted, however, that many antidepressants can also worsen sleep.
 
Neuroleptics 
Neuroleptics should not generally be used as for treating insomnia due to their side-effects. Antihistamines, such as alimemazine, clemastine and hydroxyzine hydrochloride, can be effective against anxiety. Levomepromazine can be tested, as can promethazine hydrochloride – the latter being indicated for insomnia and one of the few medications suitable for pregnant women.
 
Emerging agents 
New products have or are expected to appear shortly on the market include: 
  • A novel orexin1 and 2 receptor antagonist which was very promising in pre-clinical studies 
  • Histamine H3 agonists 
  • GABA agents, SEGA (Selective extrasynaptic GABA Agonists) with both GABA agonist e.g. gabaxadol and GABA reuptake inhibitor e.g. tiagabine
OTC, complementary and alternative therapies 
There is not yet enough evidence supporting these therapies for insomnia. There are reports of the positive impact of acupuncture, valerian, passionflower, chamomile, but the evidence is less convincing for hypnotherapy or other herbal remedies. 
 
Light therapy, efficient for adjusting the circadian rhythm, has also been reported to have a positive effect on sleep in the elderly. 
 
Prescribing 
When prescribing medication it is important to recognise the type of insomnia in order to select the most appropriate drug. It is for example unwise to recommend a short-acting hypnotic at bedtime for someone who can fall asleep easily but has difficulties in maintaining sleep. 
 
One should exercise caution with sedative/hypnotic use in the following cases: 
  • Obstructive sleep apnoea syndrome (OSAS) or snoring 
  • Elderly patients 
  • Excessive alcohol consumption 
  • Pregnancy 
  • Renal, hepatic or pulmonary disease 
  • Need to maintain alertness (e.g. hazardous occupation) during usual sleep period – for instance in shift workers 
  • Concomitant use of other drugs 
  • Suicidal tendencies 
Adverse effects of hypnotics include: 
  • Performance decrements – the longer the half-life, the greater the effect 
  • Cognitive impairment: anterograde amnesia 
  • Incoordination: falls and hip fractures
  • Motor vehicle accidents 
  • Possible increased mortality. 
Rebound insomnia 
One of the major side effects of hypnotics besides possible dependency is rebound insomnia. There are four determinants: 
 
1. Dose: the higher the dose, the greater the rebound 
2. Half-life: Long-acting drugs have less rebound because they self-taper 
3. Duration of administration: the longer the duration, the more intense the rebound 
4. Individual differences: the poorer the basal sleep, the higher the probability of a rebound
 
It is noteworthy that increasing the dose will rarely be more effective but will produce more side effects 
 
There are also some other side effects, such as increased risks of breathing disorders (due to relaxation), morning drowsiness, the possibility of hangover or temporary memory impairment.
 
Short term insomnia (acute situational insomnia):
For short-term insomnia, provide general recommendations about sleep and sleep hygiene, as above, and address anxiety. Prescribe a short lasting hypnotic (benzodiazepine agonist) using the lowest effective dose for the shortest amount of time, for example, zaleplon (T_ 1.0 – 1.4 hrs), zopiclone (T_ 4 – 6 hrs) or zolpidem (T_ 1 – 3 hrs). All these have a short half-life which means less daytime sleepiness. 
 
The treatment period should usually not exceed three weeks. Consider using intermittent doses and treatment-free days. Discontinue the hypnotic gradually and re-evaluate the patient frequently.
 
Management of chronic insomnia:
Chronic sleep disturbance is often secondary to somatic or psychiatric illness. Identify and treat the underlying medical or psychiatric condition (e.g. anxiety). There are three treatment options: 
  • Psychological or behavioural therapy. CBT has been reported to be effective for treating insomnia and its effects may be more durable than medication. It is often recommended as a first-line option for insomnia. 
  • Pharmacological therapy 
  • A combined approach, which is the most rewarding. 
Consider a tailored approach as far as possible. 
 
Insomnia and its management in the elderly
Trouble falling asleep or maintaining sleep, waking too early or not feeling rested are some of the usual complaints of older adults. The causes can be multiple, such as poor sleep hygiene, medical conditions, medications or circadian changes (older adults experience a shift in their circadian rhythms causing them to become sleepy in the early evening and wake up too early in the morning). 
 
Bad sleep at night is often associated with increased daytime sleepiness leading to napping (other factors contributing to daytime napping can be night-time or daytime use of long-acting sedating agents). Napping, in turn, may have a negative impact on night sleep. 
 
Treatment in the elderly falls into four categories: 
  • Identification and treatment of recognised medical causes for insomnia: sleep apnoea, gastrointestinal problems, movement disorders (such as PLMD: periodic limb movement disorder), restless legs, parasomnia (abnormal behaviour while asleep), urge to urinate, medical and neurodegenerative disorders. Note that polypharmacy is common among this population. 
  • Cautious treatment with sedative and sleep medication 
    • Always use caution when prescribing medicines for the elderly, especially hypnotics. Start with half the usual adult doses. Watch for possible interaction between different medications (common in this population) enhancing possible side effects. 
    • Avoid benzodiazepines, which increase risks of daytime sedation, falls and cognitive impairment. Use hypnotics such as zolpidem and zopiclone for as brief a period as possible – and not daily and not exceeding a couple of weeks. Medication should be given early to avoid daytime sleepiness and inadvertent napping. Antipsychotics should not be used unless there is evidence of severe behavioural symptoms. 
     
  • Environmental and circadian adjustments: Modification of sleep habits, e.g. avoiding long or multiple napping, or moving a short nap to an earlier time, cutting back on stimulants such as caffeine and avoiding late or heavy meals. 
  • Cognitive behavioural therapy, physical activity (and even a gentle yoga programme) can be very helpful.
The urge to urinate at night (nocturia), frequent in the elderly, is a common cause of sleep interruption. Urine excretion changes with age as well as bladder functioning and other anatomical/physiological changes - benign prostate hyperplasia is a common cause of obstruction in men. A pharmacological approach may involve alpha-adrenoreceptor blockers for mild prostatic symptoms, low dose diuretics before bedtime, desmopressin etc. 
 
Behavioural therapy consists of training voiding and avoidance of fluids, especially caffeinated or alcoholic beverages, late in the evening. 

 

Gaby Badre, Consultant at the London Clinic; Medical Director SDS Kliniken; Associate Professor, Gothenburg University

 

References

  1. 1. Connor J, Norton R, Ameratunga S, et al. Br. Med. J. 2002;324(7346):1125 
  2. 2. Hatoum et al. NSF Gallop Poll 1998 
  3. 3. Walsh J, Coulouvrat C, Hajak G. Sleep 34(8), 997-1011 
  4. 4. National Center for Sleep Disorder Research, National Institutes of Health 
  5. 5. Ohayon M, Reynolds C. Sleep Med. 2009;10:952–60 
  6. 6. Hossain J, Shapiro C. Sleep and Breathing. 2002;6(2):85–102

 

This article was first published in our sister publication, the British Journal of Family Medicine.