Bartlett Insomnia

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					                                    MedicineToday      PEER REVIEWED ARTICLE       CPD 1 POINT

                                                diagnosis and management
                                   Difficulties with sleep onset, sleep maintenance or early waking can be distressing and

                                   have a negative impact on quality of life.

DELWYN J. BARTLETT                 Insomnia is a common complaint in general prac-          prevalence was reported to be 32%.7 This is similar
PhD, MAPS                          tice.1,2 Patients typically present with a distressing   to the figure reported in an epidemiological review,
LYNNE PAISLEY                      difficulty in sleep initiation, sleep maintenance,       which found that approximately 33% of the
MPsych, MAPS                       early waking or a combination of these symptoms          general population report at least one insomnia
ANUP V. DESAI                      where wakefulness in bed is longer than 30 min-          symptom, such as difficulty initiating sleep or
MB BS, PhD, FRACP                  utes.3 Insomnia is chronic when symptoms are             maintaining sleep or having nonrestorative sleep.8
                                   present for at least one month and occur more            The prevalence is lower when daytime dysfunction
Dr Bartlett is Co-ordinator of     than three times per week.4,5 Insomnia has a nega-       is added to the definition (9 to 15%), but it has a
Medical Psychology, Sleep and      tive impact on quality of life, decreasing mood,         broader range (8 to 18%) when insomnia is
Circadian Research Group,          increasing absenteeism and reducing economic             defined according to sleep dissatisfaction.8
Woolcock Institute of Medical      productivity; however, objective performance is              Age and gender influence the prevalence of
Research, and Consultant           not necessarily impaired.6                               insomnia. Women are more likely than men to
Psychologist, Centre for                                                                    report insomnia symptoms, daytime dysfunction
Respiratory Failure and Sleep      Prevalence                                               and sleep dissatisfaction. Insomnia increases in
Disorders, Royal Prince Alfred     Estimates of the prevalence for insomnia in              the peri- and postmenopausal phases. For both
Hospital, Sydney.                  the general population range from 4 to 48%,              men and women, insomnia symptoms become
Ms Paisley is a Clinical           d e p e n ding on the definition used. In a 2004         more common with increasing age.9 However,
Psychologist, Sleep and            survey of young drivers conducted in NSW, the            the relationship between age and sleep difficulties
Circadian Research Group,
Woolcock Institute of Medical
Research, and a TAFE Student                •   Insomnia can have a negative impact on quality of life, decreasing mood, increasing
Counsellor, Sydney.                             absenteeism and reducing economic productivity. However, objective performance is
Dr Desai is Sleep Physician,                    not necessarily impaired.
Department of Respiratory and               •   Insomnia is often a trigger for the onset of depression. It has been estimated that 40 to
Sleep Medicine, Royal Prince                    50% of individuals with insomnia also experience a mental disorder such as depression.
Alfred Hospital; Senior                         There is also a considerable overlap between generalised anxiety disorder and insomnia.
Researcher, Woolcock Institute              •   Increased sleepiness is not usual in primary insomnia and should be explored in patients
of Medical Research; Clinical                   presenting with insomnia. Causes of increased sleepiness include sleep disorders
Senior Lecturer, University of                  (such as obstructive sleep apnoea and restless legs syndrome), medical and psychiatric
Sydney; and a Consultant                        conditions (particularly depression) and substance abuse.
Physician in private practice at            •   Cognitive behavioural therapy (CBT) is the most efficacious treatment of insomnia,
the Brain and Mind Research                     improving total sleep time and general sleep quality and reducing sleep latency times
Institute, Sydney, NSW.                         and waking after sleep onset. More importantly, it shifts cognitions about sleep into a
                                                more positive framework.
                                            •   Pharmacotherapy may be used for short term management of insomnia, although it is
                                                probably not the best first line option. Benzodiazepines and nonbenzodiazepine GABA
                                                receptor agonists are the most commonly used drugs.

14   MedicineToday ❙ August 2006, Volume 7, Number 8
is less clear when daytime consequences and sleep
dissatisfaction are considered.                                                           Insomnia

Insomnia is classified as primary or secondary.
Primary insomnia may be:
• idiopathic, arising in childhood
• psychophysiological, arising from a maladaptive
   conditioned response to an acute stressor
   where the bed environment is a place of
   heightened arousal
• a paradoxical or sleep state misperception,
   characterised by a mismatch between the                                         PIC NOT AVAILABLE
   patient’s sleep reports and objective
   polysomnographic findings or actigraphy.
Secondary insomnia may be associated with:
• active psychosocial stressors (adjustment
• unhealthy sleep behaviours
• an active psychiatric disorder, such as anxiety
   or depression
• another sleep disorder, such as a breathing-
   related sleep disorder or restless legs
   syndrome, or another medical condition,
   such as chronic pain, nocturnal cough or hot
• a drug or substance – consumption or
   discontinuation of medications, drugs of
   abuse, alcohol or caffeine.5

A thorough history should be taken. This enables
the clinician to explore factors that are associated
with increased sleepiness but are not usual in pri-
mary insomnia, including other sleep disorders
(obstructive sleep apnoea, restless legs syndrome,
narcolepsy or cataplexy, bruxism, somnambulism),
medical and psychiatric conditions, and substance       are often seen as a form of insomnia; however, the
abuse (drugs and alcohol).                              individuals sleep well but the sleep is not synchro-
   Circadian rhythm sleep disorders may be pre-         nised with their environment.
sent in patients who have difficulty with sleep onset       When assessing the development of insomnia,
until approximately 2 a.m. but can then achieve a       it is useful to recall the ‘three Ps’: Predisposing,
consolidated sleep (delayed sleep phase syndrome),      Precipitating and Perpetuating factors (see the
as found in 7% of young adults and often associ-        box on page 16).10
ated with a mood disorder. In older adults, it is
more common to see an abnormally early sleep            Insomnia and psychiatric disorders
onset, between 6 and 8 p.m., and waking between         Insomnia and psychiatric disorders are often
1 and 3 a.m. (advanced sleep phase syndrome),           concurrent: it has been estimated that 40 to 50%
which is less likely to be associated with a mood       of individuals with insomnia also experience a
disorder. These circadian rhythm desynchronies          mental disorder.11 In the past, insomnia was seen

                                                                                            MedicineToday ❙ August 2006, Volume 7, Number 8   15

                                                                                                        compared with zopiclone.17
  Factors in the development of insomnia                                                                   Regardless of whether CBT is adminis-
                                                                                                        tered in individual or group settings, it
  Predisposing factors                                                                                  does improve total sleep time and general
  Predisposing factors for the onset of insomnia include a familial predisposition or learnt            sleep quality and reduce sleep latency
  behaviour, unrecognised and untreated anxiety, worrisome thoughts, and elevated stress                times and waking after sleep onset. More
  response with metabolic consequences.                                                                 importantly, it positively alters cognitions
                                                                                                        about sleep.18
  Precipitating factors
  Precipitating factors can be summed up with the question of ‘Why now?’ Common                         Cognitive therapy
  examples include an acute response to stressors from relationships, family and work, as               Cognitive therapy comes from the under-
  well as economic, environmental and circadian rhythm factors (including jet lag). For most            standing that how we feel is a result
  people, sleep returns to normal when the stressor or other factor is removed.                         of how we think.19 If we are thinking
                                                                                                        negative thoughts, we’ll feel negative!
  Perpetuating factors                                                                                  Cognitive therapy aims to help patients to
  Perpetuating factors, which may be psychological or behavioural, are a consequence of                 recognise the connection between
  insomnia but also maintain it. Psychological factors include:                                         thoughts, mood and behaviour, and to
  •    misattributions about the causes of insomnia                                                     explore and experiment with other, more
  •    catastrophising about sleep needs                                                                helpful ways of thinking. An example of a
  •    expectation of a bad night’s sleep                                                               common unhelpful thought is, ‘I must
  •    anxiety, stress or depression.                                                                   have eight hours of sleep to be able to
  Behavioural factors include:                                                                          function the next day’. When individuals
  •    irregular getting up time                                                                        can identify unhelpful thoughts, the next
  •    no structure to the day or night (such as having no regular employment)                          step is to help them to interpret, challenge
  •    staying in bed for long periods when awake                                                       and substitute them with more realistic
  •    long naps                                                                                        thoughts. For example, ‘Eight hours sleep
  •    no ‘wind down time’ before bed.                                                                  would be nice, but I have managed to
                                                                                                        function with less in the past’. Reframing
                                                                                                        unhelpful thoughts is a key factor in
as a symptom of depression, but it is now               tions, most likely reflecting psychological     improving self-efficacy in regard to sleep.20
known that insomnia often precedes                      stress associated with inadequate long
depression. Insomnia is a risk factor for:              term solutions.13                               Behavioural therapies
• depression, either as an early                                                                        The two most effective behavioural thera-
    symptom or as                                       Nonpharmacological treatment                    pies or treatments for insomnia are stim-
    a prodromal sign of a recurrent                     CBT                                             ulus control therapy and sleep restriction
    episode,1 and suicide, when recurrent               CBT is the most effective nonpharmacolog-       (bed restriction), which are described in
    nightmares are present2,12                          ical treatment for insomnia.14-16 It involves   the box on page17.21 These treatments are
• generalised anxiety disorder, which is                challenging maladaptive behaviours and          often difficult to instigate, but a key mes-
    associated with increased autonomic                 cognitions that maintain insomnia and           sage is that having insomnia is difficult, so
    arousal and worry.                                  introducing healthy sleep behaviours.           it makes sense that successful treatment
    There is a considerable overlap between             Patients become more aware of their             may also require perseverance.
generalised anxiety disorder and insom-                 unhelpful thoughts about sleep and learn
nia.13 However, it is somewhat difficult                how to manage them.                             Education about healthy sleep or
to determine whether anxiety and stress                     Performing CBT is more time consum-         sleep hygiene
symptoms precede the insomnia or are a                  ing for clinicians than prescribing hypnotic    There are many myths about sleep, and
consequence. Although research has not                  medications, but it is more effective in        challenging erroneous beliefs allows
defined a personality disorder associated               both the short and long term. Very recent       patients to be more aware of their current
with insomnia, there appears to be a simi-              research has shown that CBT increases           responses to not sleeping. Educating
larity in terms of coping behaviours with               slow wave sleep and sleep efficiency as mea-    patients about behaviours known to inter-
patients who have chronic health condi-                 sured by polysomnography at six months,         fere with sleep, such as use of caffeine,

16    MedicineToday ❙ August 2006, Volume 7, Number 8
alcohol and nicotine, daytime napping,         needs to become part of patients’ usual            commonly used drugs in Australia, with
timing of exercise and what not to do in       lifestyle, a means of having ‘time out’ in         the latter group having a more favourable
bed are strategies for maintaining good        which they learn to recognise increased            safety profile.
sleep behaviours. The bed needs to be          stress responses and do something posi-
comfortable and the bedroom quiet and          tive for themselves.                               Benzodiazepines
dark, so that the patient can look forward                                                        Benzodiazepines target the GABA recep-
to sleep time. Setting aside some wind         Pharmacotherapy                                    tor, nonselectively stimulating the GABA
down time is an important component of         Pharmacotherapy is effective in inducing,          receptor subunits. In short term, rando-
relearning sleep.                              maintaining and consolidating sleep. It is         mised, double-blind, placebo-controlled
    Exercise, exposure to early morning        indicated for short term management of             trials, benzodiazepines have been shown
light and relaxation therapy are a good        insomnia, although it is probably not the          to reduce sleep onset times, increase total
combination. Exercise reduces muscle           best first line option.24                          sleep duration and improve sleep conti-
tension and physiological arousal, pro-           Many pharmacological agents have                nuity.25 However, they decrease slow wave
moting better sleep, and improves mood.        been used to initiate and maintain sleep.          sleep and rapid eye movement (REM)
Exercising in the morning allows the indi-     Benzodiazepines and nonbenzodiazepine              sleep and increase lighter, stage two
vidual to ‘get out there and do something’,    GABA receptor agonists are the most                sleep.26,27 Therefore, benzodiazepines
which is a more positive behaviour than
lying awake waiting for more sleep that is
unlikely to happen. Exercising in the            Behavioural therapies for insomnnia
evening artificially raises core body tem-
perature and must be completed at least          GPs can instigate stimulus control therapy and sleep restriction (bed restriction), along with
three to four hours prior to expected bed        an explanation that changing present sleep habits can lead to a ‘no insomnia’ outcome.
time (to allow the body to cool down,
which is necessary for sleep onset). A good      Stimulus control therapy
aim is about 30 minutes of exercise per          The aim of stimulus control therapy is to reassociate the bed and bed environment with
day, which can be gentle for patients            successful sleep.1,22 Instructions that can be given to patients include:
with reduced physical status.                    • Go to bed only when you are drowsy.
    A constant getting up time is crucial in     • Limit activities in bed to sleep and sex.
setting sleep boundaries. Getting up at the      • Get up at the same time every morning.
same time, regardless of the quality of the      • If you are unable to sleep within about 15 minutes, get up (this is the ‘quarter-hour rule’).
previous night’s sleep, means there is a            Go to another room and do something nonstimulating, such as reading in dim light,
definite end to the sleep time and is more          listening to music or performing relaxation or breathing exercises. Do not surf the
important than having a regular bedtime.            internet, watch television or catch up with work or household tasks – you need to feel
Early morning light also resets the brain’s         less tense and more ready for sleep before going back to bed. Keep light levels low.
sleep clock. Exposure to outside early              Repeat the process as many times as necessary to facilitate faster sleep initiation.
morning light is most effective, and can be
achieved in combination with exercise.           Sleep restriction
Sunglasses or a hat with brim should not         Spending more time in bed, supposedly to increase opportunity for sleep or at least ‘rest’,
be worn when out early.                          results in less consolidated sleep, more time spent in bed awake and associated increased
    Relaxation reduces physical and men-         anxiety about not sleeping. Matching time in bed with reported sleep time increases the
tal arousal but is less effective as a stand     homeostatic drive for sleep.23
alone treatment than as part of a combi-            Sleep restriction involves decreasing the time spent in bed by 30 minutes every three
nation of treatments. Relaxation tech-           to four days, from either bedtime or getting up time, until the time spent in bed matches
niques that put pressure and effort onto         the time spent sleeping. Note that less than five and a half hours is not usually
sleep, increasing the overarousal response,      recommended. Time spent in bed is then gradually increased as sleep improves.
should not be used as a means of getting            Patients should be involved in the process. Help them to estimate their sleep efficiency
to sleep.1 Relaxation techniques include         (usual sleep time divided by time spent in bed). For example, if six hours are spent sleeping
progressive muscle relaxation, focused           out of eight hours in bed then sleep efficiency is 75%. Good sleepers have a sleep efficiency
breathing strategies, imagery training,          of more than 85%, which means that sleep time and time in bed are relatively matched.
meditation and hypnosis. Relaxation

                                                                                                MedicineToday ❙ August 2006, Volume 7, Number 8    17

should be used for the shortest time pos-                     oxazepam (Alepam, Murelax, Serepax),                       and slurred speech. Enhanced sedation
sible, with the duration of use defined                       are most commonly used because they                        and respiratory depression are possible
and contracted with the patient.                              minimise residual daytime drowsiness                       with concurrent use of other CNS depres-
   Benzodiazepines differ mainly in their                     and psychomotor impairment, which can                      sants (e.g. alcohol, antidepressants).
pharmacokinetic properties. Agents that                       be particularly problematic in the elderly.                   Tolerance to the hypnotic effects of
have relatively short half-lives, temaze-                     The common adverse events include over-                    benzodiazepines develops rapidly on
pam (Normison, Temaze, Temtabs) and                           sedation, light-headedness, memory loss                    repeated administration. Dependence is

                                                             A management guide to insomnia

                                                       Patient presents complaining of insomnia

                                                                            Take a detailed history

                                                       Assess whether severe anxiety or depression is present

               Initiate behavioural treatment – stimulus                                                                 Consider pharmacotherapy
                                                                               Absent                Present
               control therapy and/or sleep restriction                                                                  as a treatment for severe
                                                                                                                         anxiety or depression

                Help patient explore exceptions, such
                as when he or she has slept well                                                                   Initiate behavioural treatment – stimulus
                                                                                                                   control therapy and/or sleep restriction

           Educate patient about importance of good
           sleep habits, including:                                                                                 Help patient explore exceptions, such
           •   a constant waking time and exposure to                                                               as when he or she has slept well
               early morning light
           •   alcohol, caffeine and nicotine reduction
           •   exercise and exercise timing
           •   relaxation practice                                                                           Educate patient about importance of good sleep
           •   diet – avoid big meals at night and high                                                      habits, including:
               protein meals                                                                                 •   a constant waking time and exposure to early
                                                                                                                 morning light
                                                                                                             •   alcohol, caffeine and nicotine reduction
                                                                                                             •   exercise and exercise timing
                                                                                                             •   relaxation practice
                                        Gradually reduce pharmacotherapy                                     •   diet – avoid big meals at night and high protein
                                        with patient’s input                                                     meals

     * If mild to moderate depression or anxiety is present, CBT can be performed without pharmacotherapy.

18   MedicineToday ❙ August 2006, Volume 7, Number 8

rare in patients taking normal therapeutic             GABA receptor subunit – by not binding         by substance abusers. Tolerance does not
doses for short periods, but approximately             all receptor subunits, it minimises anxi-      appear to develop to the hypnotic effects of
one-third of patients on long term treat-              olytic, myorelaxant and anticonvulsant         zolpidem after intermediate (four to five
ment have difficulty stopping or reducing              effects while preserving hypnotic effects.     weeks) treatment.30,31 Open label studies
their dosage.28 Rebound insomnia is char-                  Zopiclone and zolpidem have compara-       extending up to one year have demon-
acterised by a worsening of sleep relative             ble efficacy to benzodiazepines in reducing    strated a lack of tolerance to zolpidem in
to baseline and is more marked when the                sleep latency and nocturnal awakenings         the long term, but the results need to be
benzodiazepine is used regularly for long              and increasing total sleep time. Zopiclone     interpreted with caution because of their
periods, but may occur after only one week             has a rapid onset (15 to 30 minutes); its      methodological limitations.32,33 Zopiclone
of low dose administration. Withdrawal                 usual elimination half-life (five hours)       generally maintains its hypnotic efficacy
needs to be slow, with small dose reduc-               increases with age.29 Zolpidem has a simi-     for a period of two to three weeks, but
tions each week for several weeks.                     lar onset of action (30 minutes); its elimi-   long term studies in small numbers have
                                                       nation half-life is shorter (2.4 hours) and    demonstrated that improvements in sleep
Nonbenzodiazepine GABA receptor                        increases with age. Common adverse             can be maintained for up to eight to 17
agonists                                               effects include bitter taste and dry mouth     weeks of treatment.29 Rebound insomnia
Two nonbenzodiazepine GABA receptor                    for zopiclone, and nausea and dizziness        is less frequent and milder with nonbenzo-
agonists are available: zopiclone (Imovane,            for zolpidem.                                  diazepine GABA receptor agonists than
Imrest) and zolpidem (Stilnox). Zopiclone                  These drugs cause less residual morn-      that seen after discontinuation of benzo-
is a cyclopyrrolone derivative that has a              ing sedation and psychomotor impair-           diazepines.
similar mode of action to benzodiazepines.             ment than benzodiazepines and do not
Zolpidem is an imidazopyridine derivative              affect normal sleep patterns. There are also   Antidepressants
with marked specificity for a particular               fewer reports of dependency and misuse         Antidepressants with sedative effects are

20   MedicineToday ❙ August 2006, Volume 7, Number 8
occasionally prescribed for insomnia, at        anticholinergic effects. There is limited        1 site on GABA receptors) and ram-
lower doses than for depression. Amitrip-       evidence of their value and clear evidence       elteon (a melatonin receptor agonist).
tyline (Endep, Tryptanol) and doxepin           of side effects.35
(Deptran, Sinequan) are most commonly                                                            Conclusion
used, with sedative properties primarily        Over the counter therapies                       CBT is the most efficacious treatment of
from their anticholinergic effects.34 Side      Valerian is commonly used as a sleep             insomnia in the short and long term. One
effects of these drugs, which occur particu-    aid, but evidence for efficacy in insomnia       of the ironies of management is that most
larly in the elderly, include anticholinergic   is inconclusive.36 Melatonin, a popular          GPs have considerable knowledge of
effects (e.g. dry mouth, blurred vision, con-   dietary supplement, cannot be recom-             CBT and insomnia strategies, but are not
stipation, urinary retention, delirium) and     mended for primary insomnia on the basis         always sure how to instigate these. They
alpha adrenergic effects (e.g. orthostatic      of current evidence;27 however, it has a role    also appear hampered by perceptions that
hypotension, dizziness). In addition, many      in managing insomnia resulting from              patients expect a script for hypnotics, which
antidepressants can exacerbate periodic         circadian disruption (e.g. jet lag, delayed      is often not the case.38 Effective communi-
limb movements. Most of the selective           sleep phase syndrome) through its circa-         cation from both sides of the consultation
serotonin reuptake inhibitors (SSRIs) will      dian phase shifting effects.37                   in relation to insomnia management is
worsen insomnia in the first few weeks                                                           important. The flowchart on page 18 may
of use.                                         Agents under investigation                       be useful in selecting treatments.         MT
                                                There are several novel hypnotic agents
Antihistamines                                  currently under investigation. These             A list of references is available on request
Antihistamines are generally less effective     include gaboxadol (a GABA agonist),              to the editorial office.
than benzodiazepines for treating insom-        indiplon (a nonbenzodiazepine com-
nia and induce daytime drowsiness and           pound that binds to the benzodiazepine           DECLARATION OF INTEREST: None.

                                                                                                MedicineToday ❙ August 2006, Volume 7, Number 8   21