In our last issue, sleep specialist Professor Gaby Badre looked at the various types of insomnia and described best practice in assessment and diagnosis. Here, he explores the various approaches to treatment and discusses how this should be tailored to the patient.


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


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 smart phone 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 to 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 behavioral 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 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, a slow-release melatonin (2mg) 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 (melatoninreceptor 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 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 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, 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 3 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 insomia. 
  • Pharmacological therapy 
  • 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 nighttime 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, gastro-intestinal problems, movement disorders (such as PLMD: periodic limb movement disorder), restless legs, parasomnia (abnormal behavior while asleep), urge to urinate, medical and neuro-degenerative 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.

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