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Insomnia
Table 1: US Food and Drug Administration-approved
with a set of tools to apply in times of stress and insomnia relapses.
Agents for the Treatment of Insomnia
Evaluation with a sleep log is needed first to determine in which phase of
sleep problems occur (e.g. difficulties falling asleep, falling asleep too early
Medication Class Duration of Half-life Use Side Effects
or too late) and usual daily sleep amounts (generally underestimated by the
Action (hours)
insomnia patients). In sleep restriction, usual daily sleep amounts are then
Estazolam BZP Intermediate 10–24 Mainly Drowsiness,
for SMI dizziness,
decreased by 30 minutes to one hour, and the patient is asked to wake at
unco-ordination
the same time each day. After a few weeks the subject feels more sleepy
and amnesia at bedtime and sleeps more consistently. Feedback and monitoring on a
Temazepam BZP Intermediate 3.5–18.4 Mainly Drowsiness,
weekly basis are needed to titrate sleep deprivation and timing and to
for SMI dizziness,
provide cognitive therapy advice.
unco-ordination
and amnesia
Pharmacological Treatment of Insomnia
Triazolam BZP Short 1.5–5.5 Mainly Drowsiness,
for SOI dizziness,
Insomnia may be treated with CBT and instruction in sleep hygiene, either
unco-ordination,
alone or in association with hypnotic medications.
18,19
As taking many of
amnesia and these drugs can become a habit, it is usually best to use pharmaceutical
rebound agents for a maximum of three days in a row (this is enough in the context
insomnia upon
of jet lag), although in some cases pharmacological treatment is more
cessation
appropriate than behavioural therapies (psychiatric context, failure of
Flurazepam BZP Long 2.3–100 # Drowsiness,
behavioural therapy). Almost all US Food and Drug Administration
dizziness,
unco-ordination
(FDA)-approved options for the treatment of insomnia (see Table 1)
18–20
are
and amnesia
GABAergic modulators acting on the benzodiazepine-binding site of the
Quazepam BZP Long 39–73 # Drowsiness,
GABA
A
receptor, a complex chloride channel composed of a large number
dizziness, of possible subunits. A typical benzodiazepine drug has anticonvulsant,
unco-ordination
anxiolitic, hypnotic, myorelaxant and amnesic properties, although different
and amnesia
compounds can have slightly different effects on the various symptoms
Zaleplon N-BZP Short 1 Mainly Drowsiness
depending on the dose. A meta-analysis of benzodiazepine use in the
BZP for SOI
treatment of insomnia showed that sleep latency for patients receiving a
agonist
Eszopiclone N-BZP Intermediate 6 SOI and Drowsiness,
benzodiazepine was 4.2 minutes shorter, and that patients slept for an
BZP SMI dizziness and
average of 61.8 minutes longer than those in the placebo group.
20
agonist unpleasant taste
The older compounds, of benzodiazepine structure have a broad effect on
Zolpidem
a
N-BZP Short 1.4–4.5 SOI Drowsiness,
many GABA
A
receptor subtypes, whereas some of the more
BZP dizziness
recent compounds that do not have a benzodiazepine structure
agonist
(zolpidem, eszopiclone, zaleplon) have a more specialised effect. This last
Ramelteon Melatonin Short 2–5 SOI Drowsiness,
receptor dizziness
property is likely to increase receptor subtype specificity,
21
and these
(MT
‘non-benzodiazepine GABA
1
/MT
2
) A
benzodiazepine receptor-binding compounds’
agonist may have more hypnotic than myorelaxant, anticonvulsant and antianxiety
SMI = sleep maintenance insomnia; SOI = sleep-onset insomnia; BZP = benzylpiperazine;
effects, although this is clearly dose-dependent. At high doses, these
N-BZP = non-benzylpiperazine; GABA = gamma-aminobutyric acid.
compounds are similar to classic benzodiazepines. Less dependence/
# Usually not recommended due to a long half-life and high likelihood of daytime sedation.
Alprazolam, lorazepam, clonazepam, siazepam and midazolam are not FDA-approved for
treatment of insomnia; however, they are very commonly prescribed as hypnotics.
a: Zolpidem has a controlled-release formulation with a dual-layered tablet: one layer releases
zolpidem immediately and a second layer provides a slower release of additional zolpidem for
maintenance of plasma zolpidem concentrations, and may be used for SOI and SMI.
In some cases, although patients
Light Therapy
experience difficulty sleeping during the
In some cases, although patients experience difficulty sleeping during the
night, maintaining sleep until the late
night, maintaining sleep until the late morning is not a problem. This is
often seen in adolescents, and is known as delayed sleep phase syndrome,
morning is not a problem.
a circadian clock disorder. Advanced sleep phase syndrome, another
circadian clock disorder, is also sometimes seen in the elderly when living
indoors permenantly. In these cases, consistent, daily light therapy can be tolerance has been suggested for these new compounds at a constant dose,
very helpful in re-training the circadian cycle (morning when delayed, and many patients can take these compounds daily for decades without
evening when advanced).
15
Light therapy may also have antidepressant significant problems. The potential abuse of hypnotic medications remains a
effects.
16
Regular exercise at scheduled times may also help. Melatonin can concern for some physicians. This may lead them to avoid or limit the use of
also be used (particularly in completely blind subjects), and in these cases pharmacological treatment for their insomnia patients; however, abuse of
low physiological doses (0.3mg) should be used.
17
However, importantly, benzodiazepine and benzodiazepine-like hypnotics is rare among insomnia
melatonin is less effective at re-setting circadian rhythms than bright patients. The use of hypnotics should be carefully evaluated in patients with
daylight or light-box exposure at an intensity of 10,000 lux. Behavioural a previous history of substance abuse or dependence, and it is good clinical
therapies are educational to the patient and can provide insomnia patients practice to monitor prescriptions and regularly assess the patient’s
46 EUROPEAN PSYCHIATRIC REVIEW
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