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Home , Nitrazepam, Promethazine, Sleep paralysis, Zaleplon, Zolpidem, Zopiclone

CMHP Review Sleep_Layout 1 26/09/2013 11:19 Page 1

Sleep disorders z Review

An update on disorders and their treatment

Michele Sie GPhC, MCMHP In the third of this series of updated reviews on the major psychiatric groups, produced in association with the College of Mental Health Pharmacy (CMHP; www.cmhp.org.uk), Michele Sie describes the main types of and their features, and provides an overview of their treatment.

leep is a fundamental necessity that is required by • Have a good routine, go to and get up all of us. Sleep requirements vary with age and S at the same time every day and avoid daytime between individuals but in general the average • Avoid stimulants such as , nicotine, chocolate requirement for a healthy adult is between seven and and six hours before bedtime 1 eight hours of sleep per night. • Take regular exercise during the day, but avoid Sleep is divided into two types. Rapid eye move- strenuous exercise within four hours of bedtime ment (REM) sleep and non-rapid eye movement • Avoid large meals close to bedtime (non-REM) sleep. REM sleep, as the name suggests, • Associate your bed with sleep. Do not watch TV or is characterised by rapid movements of the eyes, while listen to music when retiring to bed in non-REM sleep there is little or no movement of • The should be a quiet, relaxing place to the eyes and any eye movement is slow.2 sleep; make sure the room is not too hot or too cold • If after 30 minutes you cannot get off to sleep then get up. Leave the bedroom and try to do something The five stages of sleep 3 else, return to bed when sleepy. This can be There are five stages of sleep. Stage 1 is superficial repeated as often as necessary until you are asleep sleep and only lasts for about five to ten minutes. It is the transition from being awake to going to sleep. Body Table 1. advice for patients movement slows down, there is some loss of muscle tone and there may be twitching or sudden myoclonic involvement jerks. During this time it is easy to be aroused. There are a number of that have Stage 2 is light sleep and accounts for around 50 been implicated in the sleep-wake cycle. During wake- per cent of sleep in adults. Muscle movement fulness there is high activity of , nor- decreases, eye movements stop, heart rate slows and adrenergic and serotonergic neurones. This activity the body temperature can drop. This stage lasts about slows down during non-REM sleep and nearly stops 20 minutes. during REM sleep, suggesting that these neurotrans- Stage 3 is the start of deep or slow wave sleep. Stage mitters have a role to play in promoting an awake 4 is also deep or slow wave sleep, lasts for around 30 state. activity is also high in wakefulness, minutes and is the restorative period of sleep. During and although it slows during non-REM sleep, it this stage it is hard to be aroused and if woken then increases in activity during REM sleep, suggesting a a period of disorientation and often occur. role in not only maintaining an awake state but also Stage 5 is REM sleep. It occurs rapidly after stage possibly in dreaming. Adenosine is considered to be 4 and accounts for around 25 per cent of sleep in a mediator of non-REM sleep, and may adults. During REM sleep, there is increased brain play a role in the transition from sleep to wakeful- activity and dreaming occurs. It is believed that pro- ness.4 Gamma-aminobutyric acid (GABA), the cessing and consolidating of information and emo- inhibitory neurotransmitter, helps induce relaxation tions occur while in REM sleep. During this time, and sleep.5 is a naturally occurring hor- heart rate and respiration increase and atonia occurs mone, produced by the pineal gland, which regulates causing a temporary . the circadian rhythm of sleep. It starts being released These five stages of sleep make up the , once it becomes dark, and continues to be released which lasts for about 90 minutes. This cycle is gener- until the first light of day. It has been shown that mela- ally repeated five to six times each night. tonin release decreases with age.6 Orexins, produced

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Review z Sleep disorders

in hypothalamic neurones, also have an important ing and maintaining sleep), hyersomnias (disorders of role in regulating the sleep-wake cycle and deficien- excessive ), sleep apnoea, and cies have been identified in narcolepsy.7 , restless legs syndrome, sleep walking, sleep terrors and disorder.8 Types of sleep disorder The prevalence of sleep disorders is hard to quan- Sleep disorders are defined as conditions characterised tify, as problems with sleep may be a symptom of by disturbances of usual sleep patterns or behaviours, another condition. It has been estimated that the that cause distress and impair daytime functioning. prevalence of sleep disorders in the general popula- The International Classification of Diseases version 10 tion could be as high as 37 per cent,9 with sleep dis- (ICD-10)8 has two main diagnostic categories – sleep orders of clinical significance and public health disorders and non-organic sleep disorders. Further importance occurring in 10 per cent of the popula- classification includes insomnias (disorders of initiat- tion.10 is the most commonly reported sleep

Medication Available Form Half-life, Licensed indication Tolerance Dependence as available hrs (adults)

Benzodiazepines

Diazepam Generic Tablets, 21-50 Insomnia (short-term use) Yes Yes solution Generic Tablets 10 Insomnia (short-term use) Yes Yes Generic Tablets 12-16 Insomnia (short-term use) Yes Yes Generic Tablets 10 Insomnia (short-term use) Yes Yes Generic Tablets, 18-36 Insomnia (short-term use) Yes Yes suspension Generic Tablets, 5-11 Insomnia (short-term use) Yes Yes (Schedule 3 oral controlled drug) solution

Z-

Zaleplon Sonata Capsules 2 Insomnia (short-term use Yes Yes up to 2 weeks) Generic Tablets 2-3 Insomnia (short-term use Yes Yes up to 4 weeks) Generic Tablets 3.5-6 Insomnia (short-term use Yes Yes up to 4 weeks)

Chloral and derivatives

Chloral hydrate Generic Mixture 8-10 Insomnia (short-term use) Yes Yes Cloral betaine Welldorm Tablets, 7-10 Insomnia (short-term use) Yes Yes elixir

Others

Melatonin Circadin Modified- 3.5-4 Insomnia in adults over No No release 55 years (short-term use) tablets Capsules, 4-5 Severe insomnia in elderly Yes Yes (short-term use) Phenergan Tablets, 10-19 Sedation and insomnia Yes No () elixir (short-term use)

*Refers to the active metabolite

Table 2. Treatments for insomnia and their licensed indications25

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disorder, followed by sleep apnoea and then restless Mild 10 legs syndrome. Sleep disorders have been associ- • rebound and insomnia ated with a number of adverse effects including • sleep disturbance 11 increased risk of road traffic accidents, medical • irritability errors,12 industrial accidents,13 obesity, type 2 dia- • attacks betes,14 hypertension,15 heart disease16 and a • decrease in performance and functioning.17 • sweating • poor concentration Insomnias • dry and Insomnias are disorders of initiating and maintaining • • sleep, leading to an inadequate quantity or quality of • muscular pain and stiffness sleep or both. Problems can include difficulty asleep, difficulty staying asleep, or early morning wak- Moderate ening, which can lead to and impairment of • perceptual changes, eg hypersensitivity to light or 13 cognitive function during waking hours. Insomnia is sound a common symptom of many mental disorders (non- • generalised feelings of distress organic) including mania and depression18 and can • flu-like symptoms also present in physical conditions (organic) such as • sore eyes pain and asthma.19,20 Insomnia affects around 20 per • decreased appetite and weight loss cent of the adult population and can be either tran- • sient, occurring in those who normally sleep well, as • depersonalisation • abnormal sensations of movements a result of exceptional circumstances such as ; short term, caused by emotional problems or a Severe (rare) serious medical condition; or chronic, relating to an • 18 enduring physical or mental health condition. It can • psychotic symptoms lead to a significant impairment in quality of life and affects the functioning and mental health of those Table 3. Symptoms of withdrawal syndrome36 affected.21 Economic implications of insomnia include costs relating to absenteeism and decreased z-hypnotics, chloral derivatives, clomethiazole, anti- productivity, as well as increased use of the GP.22 and melatonin.25 , z-hyp- notics, chloral derivatives and clomethiazole all act Treatment of insomnias by binding to the GABAA receptor and enhancing the Non-pharmacological approaches are recommended effect of GABA.26,27 Activation of this receptor leads as first-line treatment of insomnia23 including sleep to an influx of chloride ions into the neurone reduc- hygiene18,24 (see Table 1), encouraging the use of ing its excitability, thereby reducing activity in the techniques to promote and maintain sleep. For brain. This results in sedation, helping to induce chronic insomnia, cognitive behavioural therapy sleep. that act as antagonists at the H1- (CBT), stimulus control therapy, sleep restriction and receptor and cross the blood-brain barrier cause seda- progressive muscle relaxation are recommended first tion.28 Melatonin, as previously discussed, is a line as they have been shown to be as effective as phar- naturally occurring hormone, produced by the pineal macotherapy and, unlike medication, the beneficial gland, which regulates the circadian rhythm of sleep.6 effects of CBT may last beyond the active treatment Hypnotics decrease time to and phase.23 If insomnia is a symptom of a mental or phys- episodes of waking in sleep as well as increasing total ical condition then the precipitating cause should be sleep time.29 They can also affect the architecture treated effectively – this often leads to a resolution of (length of stages) of sleep. Benzodiazepines suppress the insomnia. If these techniques are ineffective then stages 3 and 4 of sleep, but only cause a slight decrease a medication may be considered.18 A short in REM sleep. Z-hypnotics shorten stage 1 of sleep course of a z-hypnotic (, zolpidem, zopi- and prolong stage 2 of sleep but have little effect on clone) is recommended first line for the management stages 3, 4 and REM sleep. Chloral derivatives do not of insomnia precipitated by a life stressor that is affect sleep architecture.26,27 Melatonin promotes expected to resolve in the near future.23 sleep initiation and helps to reset the circadian clock, A number of different classes of medication are allowing uninterrupted sleep. It has also been shown licensed as hypnotics. These include benzodiazepines, to improve next day functioning.30

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Most medications used to treat insomnia can cause diazepine or a z-hypnotic should not be prescribed the tolerance and dependence (see Table 2).25 Tolerance other. Switching between these two classes of hypnotics occurs following continued administration of a med- should only occur if the adverse effects experienced ication and is characterised by a decrease in suscepti- could be directly related to a specific agent.24 bility to the medicinal effects.31 Tolerance has been The therapeutic use of some older hypnotics has observed with all currently licensed hypnotics with the also been questioned. Chloral derivatives are now con- exception of melatonin. Dependence occurs when sidered less suitable for prescribing due to their adverse there is a need to take repeated doses of a medication effects and abuse potential and clomethiazole is only to maintain wellbeing or to prevent withdrawal symp- recommended for use in insomnia in those over 55 toms and can be psychological, physical or both.32 years of age.25 Clomethiazole only has evidence to sup- is a craving or compulsion port its use in this age group when other hypnotics have to continue using the medication to maintain a feel- failed, although it is rarely used now due to the risk of ing of wellbeing. is the need to accidental overdose and respiratory depression.25 continue taking medication to prevent physical with- Some hypnotics cause a hangover effect, i.e. seda- drawal effects. Withdrawal syndrome is most often asso- tion and impairment of psychomotor performance, ciated with the benzodiazepines33 (see Table 3), but including driving ability and memory on the following withdrawal symptoms have also been documented with day. To avoid this, it is recommended that medications chloral derivatives, clomethiazole and z-hypnotics.34,35 with a short half-life of between four and six hours To reduce the risk of dependence and tolerance, it should be used. Medications with shorter half-lives than is recommended that hypnotics are only used in severe this can give rise to early morning wakening.36 and disabling insomnia, which is causing extreme dis- tress. For transient insomnia, only one or two doses Excessive daytime sleepiness, and should be given and for short-term insomnia, hypnotics narcolepsy should only be used for a limited course of up to three Excessive daytime sleepiness occurs in about 3-5 per weeks, preferably intermittently. In chronic insomnia, cent of the population and can be caused by poor hypnotics are rarely beneficial and the underlying ill- sleep quality and duration due to either a concurrent ness needs to be managed.25 If hypnotics that cause a sleep, mental health or medical disorder. withdrawal syndrome are used for more than three Hypersomnia is characterised by excessive daytime weeks they should be withdrawn slowly. For those wish- sleepiness or daytime sleep episodes that cause severe ing to withdraw from long-term, short-acting benzo- distress or impairment in functioning and occur diazepines, switching to , a long-acting almost daily but are not part of a concurrent sleep, benzodiazepine, can be useful (see Table 4). Diazepam mental health or medical disorder. It is hard to quan- can then be reduced slowly, for example by one-eighth tify the prevalence of hypersomnia as symptoms of of the daily dose every fortnight.25,33,36 excessive daytime sleepiness can occur with any sleep NICE carried out a Technology Appraisal on the disorder that causes a loss of night-time sleep.18 newer hypnotics in 200424 and reported that there was Narcolepsy, a condition that normally presents with a lack of compelling evidence to distinguish between excessive daytime sleepiness, can be distinguished from the z-hypnotics and the shorter-acting benzodiazepine other sleep disorders by the presence of cataplexy (a hypnotics and concluded that prescribing decisions sudden and transient loss of muscle tone, while awake, should be made on a cost basis. They recommended usually triggered by strong such as laughing), that patients who had not responded to either a benzo - sleep paralysis and sleep-related . These symptoms are believed to be characteristics of REM Benzodiazepine Approximate equivalent sleep, which do not normally occur during the awake dose to diazepam 5mg state. Narcolepsy is reported to affect around 0.05 per cent of the population and normally begins between 15mg the ages of 10 and 20 years.18,37 Recent evidence has Loprazolam 0.5-1mg suggested a strong correlation between decreased lev- Lorazepam 0.5-1mg els of orexins (also called hypocretins) and narcolepsy.38 Lormetazepam 0.5-1mg Nitrazepam 5mg Treatment of excessive daytime sleepiness, hypersomnia and 15mg Temazepam 10mg narcolepsy Excessive daytime sleepiness should be managed by Table 4. Diazepam equivalent doses25,36 treating the underlying cause.37 Guidance from the

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Treatment Licensed for Shown to be effective in: * narcolepsy Daytime Disrupted Cataplexy Sleep-related Sleep paralysis sleepiness sleep hallucinations

Modafinil Yes Yes No No No No Yes Yes Yes Yes Maybe Maybe No Yes No No No No Dexamfetamine Yes Yes No No No No No Maybe No Maybe Maybe Maybe No No No Maybe Maybe Maybe † SSRIs No No No Maybe Maybe Maybe No No No Maybe Maybe Maybe Reboxetine No No No Maybe Maybe Maybe

* Yes = there is evidence provided by randomised trials or meta-analysis of randomised controlled trials; maybe = there is evidence provided by poorly conducted case-control or cohort studies, case series or expert opinion † is licensed for the adjuctive treatment of cataplexy associated with narcolepsy

Table 5. Treatment options for the symptoms of narcolepsy39

American Academy of Sleep Medicine39 recommends release. It may also activate orexin neurones treatment options for hypersomnia and narcolepsy and reduce GABA. increases wakefulness based on the current evidence available. For hyper- and latency to sleep, as well as reducing non-REM and somnia, modafinil may be effective for the treatment REM sleep. Dexamfetamine, methylphenidate and of daytime sleepiness due to , sodium oxybate all have abuse potential and this has Parkinson’s disease, multiple sclerosis or myotonic led to modafinil (which has less abuse potential) being dystrophy. Methylphenidate may also be effective for the first-line treatment for narcolepsy. the treatment of daytime sleepiness due to myotonic dystrophy. Lithium carbonate may be effective for Obstructive sleep apnoea treatment of recurrent hypersomnia. None of these The most common sleep-related breathing disorder is treatments are licensed for hypersomnia and their obstructive sleep apnoea, occurring in approximately use would be off-label. The American Academy of 3-7 per cent of men and 2-5 per cent of women. It is Sleep also recommends a number of treat- more likely to occur in patients with cardiac or meta- ment options for the different symptoms experienced bolic disorders. Risk factors include obesity, upper air- in narcolepsy (see Table 5). way abnormalities, male gender, menopause and age. It is characterised by loud , followed by apnoea The pharmacology of narcolepsy treatments4,39-42 (a period of silence, when breathing ceases due to com- The stimulants dexamfetamine and methylphenidate plete airway obstruction), which can last up to 90 sec- block the reuptake of, and enhance the release of, onds. Following each apnoea there is a wakening noradrenaIine, dopamine and , all of which episode and these episodes occur many times during could be responsible for their wake-promoting effects. the night, although those affected do not normally These stimulants have been shown to increase arousal, recall these arousals. This interrupted night-time sleep decrease sleepiness, increase latency to sleep and pro- leads to excessive daytime sleepiness, which in turn duce a severe decrease in REM sleep. The mode of affects quality of life and alters social, familial and pro- action of sodium oxybate (the sodium salt of gamma fessional performance.43 Treatment for this condition hydroxybutyrate) is unclear. It has been shown to includes lifestyle changes such as weight loss, smoking reduce the number of episodes of cataplexy and day- cessation and avoidance of alcohol. and sleep- time napping, to improve excessive daytime sedation, ing tablets at night are not recommended as these can with restoration of fragmented sleep, as well as increase decrease dilation of the airways, thus worsening the the duration of stage 3 and 4 non-REM sleep. Although condition. Obstructive sleep apnoea may also be treated the mode of action of modafinil is unclear, it may act with continuous positive airway pressure (CPAP), which by blocking dopamine and noradrenaline reuptake as forces air into the lungs via a face mask, keeping the well as increasing dopamine, serotonin, glutamate and airways open and preventing the apnoea.44

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Restless legs syndrome anxiety that can cause difficulty in returning to sleep, Restless legs syndrome is a neurological disorder asso- leading to significant distress that may or may not ciated with pain or paraesthesia in the legs that is tem- affect daytime functioning.18 Between 2 and 5 per cent porarily relieved by movement; it is often of the adult population suffer from frequent night- accompanied by periodic limb movements during mares and these may be idiopathic or part of post- sleep. The prevalence of the disorder has been traumatic disorder (PTSD).49 Some medications reported to be up to 10 per cent and it occurs more may be associated with including , frequently in women and those over 65 years of age. , beta-blockers and , and Restless legs syndrome expresses a circadian rhythm, these should be avoided.25,36 For nightmares related being worse in the evening and at night and easing to PTSD, , an alpha-adrenoceptor blocker, has in the morning. It is caused by a decrease in been shown to be effective in reducing nightmare fre- dopamine function in the CNS.13,45 quency, although it must be taken long-term as on ces- As expected, have been sation nightmares commonly recur. , an shown to alleviate the symptoms of restless legs syn- alpha2- , has a small evi- drome in 70 to 100 per cent of patients and are the dence base for reducing nightmares in refugees at a first-line treatment option. , dose of 0.2-0.6mg daily in divided doses and may be and are all licensed for the treatment of an option if prazosin is not effective.50 moderate to severe restless legs syndrome.46 For idiopathic nightmares, CBT, including system- , and are not atic desensitisation, lucid dreaming techniques and recommended due to the risk of heart valve dam- image rehearsal therapy have been shown to be effec- age.45 Levodopa has also been shown to be effective tive in reducing nightmare frequency.49,50 There is but around 80 per cent of patients develop rebound, no effective pharmacological treatment for idiopathic in which symptoms return within a few hours follow- nightmares. ing administration, or augmentation, in which symp- REM sleep behaviour disorder occurs when there is a toms occur earlier in the evening, prior to treatment. loss of the muscle atonia that normally occurs in REM The dopaminergic agonists may also cause rebound sleep. This leads to motor activity, generally in response and augmentation but to a lesser extent than levo - to a nightmare of being attacked or chased, which can dopa.47 There is limited evidence for the use of opi- often be of an unexpected and violent nature. If oids, , , and awoken, there is vivid recall of the .18 It can lead clonidine, but it is unclear if the benefit/harm bal- to accidental injury to oneself or one’s partner. The ance is advantageous. 45 prevalence is estimated to be around 0.5 per cent of the associated with causing or exacerbat- population. It is more common in older males and may ing restless legs syndrome include some antidepres- be a prodromal symptom of a neurological disease such sants, and sedating antihistamines. If as Parkinson’s disease or Lewy body . It has these medicines are prescribed in those presenting been reported as an of , flu- with symptoms of restless legs syndrome, considera- oxetine and impipramine in combination, venlafaxine, tion should be made to reducing and stopping where and beta-blockers.51 , 0.5- possible or switching to an alternative agent.45,48 2.0mg at bedtime, has been shown to resolve or sub- stantially reduce symptoms in up to 90 per cent of those Sleep walking, sleep terrors and treated, but long-term treatment is required as symp- Sleep walking, sleep terrors and nightmare disorder toms often return on cessation of clonazepam.52 It are all types of . Parasomnias are should be used with caution in patients with dementia, described as abnormal behavioural or physiological gait disorders or concomitant obstructive sleep apnoea. events occurring in association with sleep, specific Mela tonin, at a dose of 3-12mg at bedtime, has also sleep stages or sleep-wake transitions.18 They are clas- been shown to be effective in treating this disorder.51 sified into two groups: disorders of REM sleep or dis- orders of non-REM sleep, as outlined below. Disorders of non-REM sleep Sleep terror disorder (night terrors) is characterised by Disorders of REM sleep episodes of disruption of sleep that usually begin with Nightmare disorder is characterised by repetitive, fright- a fearful scream or cry. There may be signs of arousal ening , occurring during REM sleep, which such as sitting up in bed with the eyes open, increased lead to the patient waking and becoming fully alert. heart rate, rapid breathing and sweating, but the indi- Those affected often have a lingering sense of or vidual remains in a deep sleep and is hard to awaken

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Medication Common side-effects

Treatments for insomnia

Benzodiazepines Drowsiness, sedation, blurred vision, unsteadiness and all of which may persist the following day

Clomethiazole Sedation, nasal congestion and irritation, gastrointestinal disturbances

Cloral and derivatives Gastric irritation, nausea and , abdominal distention, flatulence, headache, tolerance, dependence, excitement, , ketonuria, rash

Melatonin Headache, pharyngitis, back pain, asthenia

Promethazine Drowsiness, , restlessness, , nightmares, tiredness, disorientation, blurred vision, dry mouth, urinary retention

Z-hypnotics Drowsiness, mild bitter or metallic after-taste (with zopiclone only), gastrointestinal disturbances, nausea and vomiting, dizziness, headache, dry mouth

Treatments for hypersomnia and narcolepsy

Dexamfetamine Palpitations, tachycardia, increased blood pressure, overstimulation, restlessness, dizziness, insomnia, , dyskinesia, , tremor, headache, dry mouth, unpleasant taste, diarrhoea, constipation, anorexia and weight loss, growth retardation in children

Methylphenidate Abdominal pain, nausea, vomiting, dyspepsia, dry mouth, anorexia, reduced weight gain, tachycardia, palpitation, arrhythmias, changes in blood pressure, cough, tics, insomnia, nervousness, weakness, depression, irritability, aggression, headache, drowsiness, dizziness, fever, arthralgia, rash, pruritus, alopecia

Modafinil Headache, dizziness, somnolence, paraesthesia, blurred vision, constipation, dry mouth, decreased appetite, abdominal pain, nausea, diarrhoea, dyspepsia, nervousness, insomnia, anxiety, depression, abnormal thinking, , weakness, tachycardia, palpitations, chest pain, vasodilatation, abnormal function tests

Reboxetine Constipation, dizziness, dry mouth, insomnia, sweating

SSRIs Anxiety or restlessness, insomnia, diarrhoea, nausea and vomiting, loss of appetite

Selegiline Nausea, constipation, diarrhoea, dry mouth, postural , dyskinesia, , sleeping disorders, confusion, hallucinations, arthralgia, myalgia, mouth ulcers

Sodium oxybate Nausea, vomiting, diarrhoea, abdominal pain, anorexia, hypertension, peripheral oedema, fainting, sleep disorders, confusion, disorientation, paraesthesia, , impaired attention, depression, drowsiness, anxiety, dizziness, headache, tremor, asthenia, fatigue, , nocturnal enuresis, arthralgia, muscle , blurred vision and sweating. Requires re-titration if a treatment interval of 14 days or more

Tricyclic antidepressants Drowsiness, blurred vision, dry mouth, constipation, urinary retention, weight gain

Venlafaxine Gastrointestinal disturbances, constipation, diarrhoea, nausea, headache, dizziness, insomnia, sweating, anxiety

Treatment for restless leg syndrome

Dopamine agonists Abnormal dreams, insomnia, dizziness, headache, somnolence, constipation, nausea and vomiting

Treatment for PTSD-related nightmares

Prazosin Dizziness, drowsiness, headache, fainting, depression, nervousness, vertigo, palpitations, oedema, nasal congestion, blurred vision, constipation, diarrhoea, dry mouth, urinary frequency, nausea, vomiting, rash, lack of energy, weakness

Table 6. Common side-effects of medications used to treat sleep disorders25

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or comfort. The episodes occur during stage 3 and 4 paroxetine, carbamazapine, diazepam and of non-REM sleep and can last up to 10 minutes, semisodium, all at low doses, being successful at man- before the individual calms down and returns to sleep. aging both sleep terror and sleep walking disorders, Unlike nightmares, there is no recall of the episode but there is a lack of controlled studies to confirm the following morning. In childhood, the prevalence their effectiveness.53 of sleep terrors is between 1 and 6 per cent, and it is more common in boys. In children, the disorder usu- Other sleep disorders ally resolves spontaneously by adolescence. In adults, Sleep disorders may also relate to either another men- the prevalence is less than 1 per cent, with episodes tal health disorder or general medical condition, or may generally beginning between the ages of 20 and 30 be substance-induced. These sleep disorders are mainly years, and the disorder being of a chronic nature. managed by optimising the treatment of the underly- There is often a family history of sleep terrors or sleep ing mental health or physical health condition, or with- walking. Fever and lack of sleep have been shown to drawing the substance causing the sleep disorder.18 increase the frequency of sleep terror episodes.53 Sleep walking disorder is characterised by episodes of Future developments complex motor behaviour initiated during sleep, There are a number of treatments currently being including rising from bed, walking about, eating and investigated in phase 2 and 3 clinical trials includ- talking. An episode is accompanied by reduced alert- ing: , a histamine H3- receptor inverse ago- ness and responsiveness and the individual can be hard nist, for the treatment of narcolepsy, cataplexy and to awaken. An episode can either spontaneously end in excessive daytime sleepiness, and ‘ADX-N05’ also for arousal with brief confusion, or the individual returns the treatment of narcolepsy and excessive daytime to bed and sleeps until morning with no recall of the sleepiness. , a melatonin MT1 and MT2- episode on awakening. Episodes also occur during receptor agonist, is currently waiting approval of stage 3 and 4 of non-REM sleep and can last from a few FDA for the treatment of non-24-hour sleep-wake minutes to half an hour. The prevalence in children is disorder, a circadian rhythm disorder that affects the between 1 and 5 per cent and, like sleep terrors, the majority of totally blind individuals who lack light disorder normally resolves during adolescence. It is perception and who therefore cannot entrain their rare for episodes to occur for the first time in adults, master body clock to the 24-hour day. , and if they do this may be associated with a sleep- the r- of modafinil, a stimulant for the related breathing disorder, hyperthyroidism, person- management of narco lepsy and shift work sleep dis- ality disorder, mood disorder or anxiety disorder.53 order, has been approved in the USA. Development Sleep terrors and sleep walking are more likely to of , an orexin OX1 and OX2-receptor occur near the beginning of sleep whereas night- antagonist, for the treatment of primary insomnia mares are more likely to occur later in the night.53 has ceased as a result of its side-effect profile.54 Treatment of sleep terror and sleep walking disorders Non-pharmacological treatments are the first-line Conclusion option for these conditions, including reduction of There are a large number of different sleep disorders, trigger factors such as stress, fever and sleep depri- ranging from disorders affecting the induction of vation.53 Some medications may cause sleep disor- sleep to disorders that cause disturbance during sleep. ders as an adverse effect. An association between Insomnia is the most prevalent disorder and should z-hypnotics and sleep walking has been documented initially be managed with sleep hygiene techniques. If and dexamfetamine, and hypnotics are necessary, they should only be used may cause night terrors.25 It is also important to short term to avoid dependence and tolerance. Sleep ensure a safe environment to reduce the risk of caus- disorders that occur in childhood generally resolve ing injury during an episode, including secure locks spontaneously around adolescence and often do not on doors and windows, and heavy curtains to protect require psychological or pharmacological treatment. windows. A consistent bedtime routine should be Most medications for sleep disorders other than maintained to reduce the risk of , insomnia are not licensed and their use would be ‘off- which may further worsen episodes.53 label’, so consent issues need to be considered and Medication is rarely indicated, particularly in chil- clearly documented. dren, unless the disorder is of a severe nature caus- ing distress and loss of daytime functioning. There Declaration of interests are reports of , , , None declared.

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