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sleep–wake cycle in man determined bypositron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method. BrainRes 1990;9:136–43.

6 Mahowald MW, Schenck CH. Dissociatedstates of wakefulness and sleep. Review.Neurology 1992;42(7 Suppl 6):44–51.

Insomnia has a major impact on humanhealth, performance, economic produc-tivity and quality of life.1,2 Insomniachronic or severe enough to merit treat-ment occurs in 8–14% of the generalpopulation.3 There are few specialisedsleep clinics in Great Britain other thanrespiratory ones (eg for obstructive sleepapnoea syndrome (OSAS)), most clini-cians do not have easy access to psycho-logical treatments, and very often thesimplest course of action is the prescrip-tion of hypnotic drugs. However, theappropriate use of hypnotics requires anaccurate diagnosis of the sleep disorderand knowledge of the pharmacokineticsand dynamics of the available drugs.

The length of total sleep in a day variesin normal adults, with an average of7–8 hours in the 20–45 year age group.Sleep time and sleep continuity aredecreased in older people and increased

daytime napping often leads to a furtherreduction in the night-time sleep. Anormal subject has several short awaken-ings during the night, most of which arenot perceived as awakenings unless theylast more than about two minutes. Therewill probably not be clear consciousness,but subjects may have occasional briefthoughts of how comfortable they feel orhow pleased they are that it is not yettime to get up, with an immediate returnto sleep. If during the short period ofwaking some factor causes anxiety oranger (eg aircraft noise, partner’s snoresor dread of being awake), progress to full awakening and remembering thisawakening in the morning are muchmore likely. The more often this hap-pens, the more subjects complain ofunrefreshing sleep. Perhaps the mostcommon cause of irritation derives from‘clock watching’: subjects check the timeon awakening, remember it and repeatthis cycle many times during the night,neglecting periods of sleep in between.This produces anger and frustration,which in turn delay return to sleep andmay promote subsequent awakenings.

Diagnosing insomnia

Insomnia is the complaint of poor sleep,with a patient reporting that the dura-tion or subjective quality of sleep isunsatisfactory. It is often accompaniedby daytime fatigue, but not usually bydaytime sleepiness – it seems that thefactors that keep people awake at nightalso serve to keep them awake in the day.To aid diagnosis of sleep disorders it is

Sue Wilson PhD, Research Fellow andHonorary Consultant

David Nutt DM FRCP FRCPsych FMedSci,Professor of Psychopharmacology,Consultant Psychiatrist

Psychopharmacology Unit, University ofBristol

Clin Med 2005;5:101–4

Assessment and

management of

insomnia

Insomnia is the subjective experience of poor or unrefreshing sleep

Insomnia has many factors that should be sought out and treated

Early intervention in acute insomnia may help reduce the likelihood of developingchronic insomnia

‘Z’ drugs have the highest ratio of efficacy to side effects and are the first-linedrug treatment

Hypnotics can be used in certain cases of chronic insomnia if the patient makes aninformed choice about the risks of dependence versus the benefits of continueduse

Key Points

KEY WORDS: cognitive behavioural therapy, hypnotics, insomnia, Z drugs

important for patients to keep a diary ofwhen they slept and how they felt abouttheir sleep. Some questions to askpatients to help determine the natureand type of their insomnia are shown inTable 1.

It is important to exclude other sleepdisorders as a cause of insomnia, partic-ularly restless legs syndrome, usuallyassociated with periodic leg movementsin sleep, and parasomnias such as nightterrors and sleepwalking. Referral to aspecialist sleep centre for objectiverecording of sleep may be necessary if the presentation is unusual or diagnosisis in doubt, and actigraphy (Fig 1) orpolysomnography may be used.

Some precipitating factors in insomniaare listed in Table 2. Timely treatment ofshort-term insomnia is valuable as it mayprevent progression to a chronic condi-tion which is much harder to alleviate.Psychological treatments are effective,4

while pharmacotherapy may be eitherunnecessary or used as a short-termadjunct. The approaches of treatment areto:

• treat any precipitating cause ifpossible

• establish good sleep habits (Table 3)

• reassure that sleep will improve

• consider hypnotic medication.

Long-term insomnia

There are various reasons why insomniacan progress to become a long-termproblem. The most common are:

• poor sleep hygiene has beenestablished and continues

• the patient has become excessivelyanxious about their sleep, spendingmuch time and effort on ‘trying’ tosleep.

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Describing insomnia • What time do you go to bed? Get up? How long does it take you to go off to sleep?

• Do you wake up a lot during the night? Does it take you a long time to get back to sleep?

• How many ‘bad’ nights do you have in a week? How does it impact on your daytime activities?

Probing other causes • How has your mood been recently? Do you manage to enjoy your social/family activities? (depression)

• Do you find you can’t keep still at night? Do your legs twitch in bed? (RLS, PLMS)

• Have you been told that you act strangely during your sleep? (parasomnias)

• Do you fall asleep suddenly during the day? Do you sometimes go weak when you’re emotionally roused, for instance when you’re laughing? (narcolepsy)

• Have you been told that you snore loudly? Or stop breathing at night? (OSAS)

OSAS = obstructive sleep apnoea syndrome; PLMS = periodic leg movements in sleep; RLS = restlessleg syndrome.

Table 1. Some questions which may be useful in a patient who is complaining aboutinsomnia.

u Fig 1. Actigraphy, an objectivemeasure of daily movement overweeks. Each horizontal line represents a24-hour period and the height of eachvertical bar represents the amount ofmovement in 1 minute. This insomniacsubject adhered to regular rising timesand other sleep hygiene measures for thefirst 8 days, then slipped back into a lessregulated regime.

Care should be taken to identify andtreat depressive and anxiety disorders inthis group of patients.

The most important factor in thetreatment of long-term insomnia is anxiety about sleep, arising from condi-tioning behaviours that predispose toheightened arousal and tension at bedtime. Thus the bedroom is associatedwith not sleeping and automatic negativethoughts about the sleeping processoccur in the evening.

Cognitive behavioural therapy

A helpful treatment approach to anxietyabout sleep is cognitive behaviouraltherapy which, together with educationand sleep hygiene measures as above, isthe treatment of choice for long-termprimary insomnia.5 However, the avail-ability of these therapies is often limitedand some patients are unwilling orunable to engage with them.

Drugs for insomnia

Most drugs used in insomnia act as ago-nists at the gamma-aminobutyric acid(GABA)-A-benzodiazepine receptor andhave effects other than their directsedating action, including muscle relax-ation, memory impairment and ataxia,which can impair performance of skillssuch as driving. Those drugs with longerduration of action are likely to affect psy-chomotor performance, memory andconcentration, and will also haveenduring anxiolytic and muscle-relaxingeffects.

Hypnotics acting at thebenzodiazepine receptor

All benzodiazepines and newer benzodi-azepine-like (‘Z’) drugs are safe andeffective for insomnia – if the compoundwith the right timing of onset of actionand elimination is chosen. Care shouldbe taken in prescribing them to patientswith comorbid sleep-related breathingdisorders such as obstructive sleepapnoea syndrome which is exacerbatedby benzodiazepines. It is important tostress that alcohol potentiates the effectsof these drugs: patients should be made

aware that if they have a drink in theevening, their sleeping pill will havegreater and longer-lasting effects whichmay have an impact on driving the nextday. The choice of drug should be deter-mined by pharmacokinetic properties.

A variety of benzodiazepines to treatinsomnia is available in UK. Theshortest-acting are temazepam, lopra-

zolam and lormetazepam, with half-livesof up to 12 hours. Zopiclone has ahalf-life of 6–8 hours, making it an effec-tive drug both for initial and mainte-nance insomnia. Zolpidem and zaleplonhave a fast onset (30–60 min) and shortdurations of action, with half-lives ofthree hours and two hours, respectively(Fig 2).

Studies of psychomotor performancein volunteers have shown that zaleplonhas no effect on psychomotor skills,including driving skills, when taken atleast five hours before testing. Thus, itcan be taken during the night, eitherwhen patients have tried getting off tosleep for a long time or if they wakeduring the night and cannot return tosleep, without hangover effect. It is theonly prescribable hypnotic that can beused in this way.

Hypnotics: tolerance anddependence

Many studies of subjective sleep qualityshow enduring efficacy of hypnotic drugsbut about half of the objective (EEG)

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Psychological Hyperarousal due to: • stress• the need to be vigilant at night because of

sick relatives or young children• being ‘on-call’

Pharmacological Prescribed drugs • certain antidepressants, especially SSRIs in first 2 weeks

Non-prescribed drugs • first 2–3 nights after withdrawal of hypnotics

• beta-blockers, beta-agonists sometimes• caffeine• alcohol• cocaine, amphetamine, other stimulants

Physical • pain• pregnancy• coughing or wheezing• respiratory and cardiovascular disorders• need to urinate• neurological disorders (eg stroke)• movement disorders• periodic leg movements of sleep

Psychiatric disorders • depression• anxiety disorder• dementia• substance misuse and withdrawal

Disruption of circadian rhythm • jet lag• shift work

SSRI = selective serotonin reuptake inhibitor.

Table 2. Some precipitating factors in insomnia.

• Keep regular bedtimes and risingtimes

• Reduce daytime napping

• Daytime (but not evening) exerciseand exposure to daylight (especiallymorning sun) are beneficial

• Avoid stimulants, alcohol andcigarettes in evening

• Establish bedtime routine (‘winddown’), use some time in early part ofevening to write down any residualissues from the current day as well asplans for the coming one

• Avoid dwelling on problems in bed

• Bed should be comfortable and nottoo warm or too cold

Table 3. Good sleep habits.

studies indicate decreased effects after4–8 weeks, implying the development ofsome tolerance. However, the necessityfor dose escalation in insomnia is rare.Both animal and human research hasshown that brain receptors change incharacter in response to chronic treat-ment with benzodiazepines, and there-fore will take time to return topremedication levels after cessation ofmedication. Features of withdrawal anddependence vary. Commonly, there is akind of psychological dependence basedon the fact that the treatment works toreduce sleep disturbance, and thereforepatients are unwilling to stop. If they dostop, there can be relapse and originalsymptoms return. Also commonly, therecan be a rebound of symptoms, with aworsening of sleep disturbance for one ortwo nights, with longer sleep onsetlatency and increased waking duringsleep.

Other drugs

Older drugs. Chloral hydrate, chlorme-thiazole and barbiturates also enhanceGABA function, but at high doses havethe additional capacity directly to openthe membrane chloride channel. Thismay lead to potentially lethal respiratorydepression and explains their low thera-

peutic ratio. These drugs have less evi-dence base for efficacy than the newerhypnotics and also have a propensity forabuse/misuse. Thus, they are very muchsecond-line treatments.

Gammahydroxybutyrate. A GABA ana-logue, gammahydroxybutyrate (GHB),works on a novel non-GABA-A receptorsystem in the brain. It is a powerful sedative/anaesthetic agent that is stronglysleep-promoting, but very short-lived in its hypnotic action. GHB is a classC controlled drug in the UK, more popu-larly known as ‘GBH’ or ‘liquid ecstasy’,abused by body builders and sometimesused for date rape. It has been known formany years that GHB is an effective treat-ment of cataplexy in narcolepsy, possiblybecause it consolidates rapid eye move-ment sleep. GHB should be licensed inEurope for this indication in 2005.

Antidepressants. There is no objectiveevidence that very low doses of tricyclicantidepressants improve sleep in primaryinsomnia. In depression, mirtazapine isuseful in patients with marked insomniaas a symptom.

Melatonin. Melatonin, the hormone pro-duced by the pineal gland during dark-ness has been investigated for insomnia

but it appears to be ineffective, althoughit seems to help in alleviating jet lag.

Over-the-counter medications. Most pro-prietary (over-the-counter) sleep reme-dies contain antihistamines. Prometh-azine reduces sleep onset latency andawakenings during the night after asingle dose, but no studies have lastedlonger than one night. There are fewcontrolled studies showing improve-ments in sleep after other antihistamines.Most antihistamine sedatives have a rela-tively long action and may cause daytimesedation. There are very few randomisedclinical trials of herbal sleep aids6 and sofar evidence for efficacy is inconsistent.

References

1 Leger D, Scheuermaier K, Philip P, PaillardM, Guilleminault C. SF-36: evaluation ofquality of life in severe and mild insomniacscompared with good sleepers. PsychosomMed 2002;63:49–55.

2 Leger D. Public health and insomnia: eco-nomic impact. Sleep 2000;23(Suppl 3):S69–76.

3 Ohayon MM, Caulet M, Priest RG,Guilleminault C. DSM-IV and ICSD-90insomnia symptoms and sleep dissatisfac-tion. Br J Psychiatry 1997;171:382–8.

4 Morin CM, Espie CA. Insomnia: a clinician’sguide to assessment and treatment. NewYork: Kluwer Academic, 2003.

5 Espie CA. Cognitive behaviour therapy asthe treatment of choice for primaryinsomnia. Sleep Med Rev 1999;3:97–9.

6 Gyllenhaal C, Merritt SL, Peterson SD,Block KI, Gochenour T. Efficacy and safetyof herbal stimulants and sedatives in sleepdisorders. Sleep Med Rev 2000;4:229–51.

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Fig 2. Approximate duration of action of hypnotic drugs.

Hyp

no

tic

effe

ct

Time (hours)

2 8 12

Zopiclone

Zolpidem

Zaleplon

Otherhypnoticdrugs

Temazepam,loprazolamlormetazepam