There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: cream
Cutaneous patch
EXCIPIENTS: May contain Butylated hydroxyanisole
▶Qutenza (Grunenthal Ltd)
Capsaicin 179 mg Qutenza 179mg cutaneous patches |
1 patch P £210.00 DT = £210.00
Cream
EXCIPIENTS: May contain Benzyl alcohol, cetostearyl alcohol (including
cetyl and stearyl alcohol)
▶Axsain (Teva UK Ltd)
Capsaicin 750 microgram per 1 gram Axsain 0.075% cream |
45 gram P £14.58 DT = £14.58
▶Zacin (Teva UK Ltd)
Capsaicin 250 microgram per 1 gram Zacin 0.025% cream |
45 gram P £17.71 DT = £17.71
Sleep disorders
Insomnia
7.1
Hypnotics and anxiolytics
Overview
Most anxiolytics (‘sedatives’) will induce sleep when given at
night and most hypnotics will sedate when given during the
day. Prescribing of these drugs is widespread but
dependence (both physical and psychological) and tolerance
occur. This may lead to difficulty in withdrawing the drug
after the patient has been taking it regularly for more than a
few weeks. Hypnotics and anxiolytics should therefore be
reserved for short courses to alleviate acute conditions after
causal factors have been established.
Benzodiazepines are the most commonly used anxiolytics
and hypnotics; they act at benzodiazepine receptors which
are associated with gamma-aminobutyric acid (GABA)
receptors. Older drugs such as meprobamate p. 363 and
barbiturates are not recommended—they have more side-
effects and interactions than benzodiazepines and are much
more dangerous in overdosage.
Benzodiazepine indications
. Benzodiazepines are indicated for the short-term relief
(two to four weeks only) of anxiety that is severe,
disabling, or causing the patient unacceptable distress,
occurring alone or in association with insomnia or short-
term psychosomatic, organic, or psychotic illness.
. The use of benzodiazepines to treat short-term ‘mild’
anxiety is inappropriate.
. Benzodiazepines should be used to treat insomnia only
when it is severe, disabling, or causing the patient extreme
distress.
Dependence and withdrawal
Withdrawal of a benzodiazepine should be gradual because
abrupt withdrawal may produce confusion, toxic psychosis,
convulsions, or a condition resembling delirium tremens.
The benzodiazepine withdrawal syndrome may develop at
any time up to 3 weeks after stopping a long-acting
benzodiazepine, but may occur within a day in the case of a
short-acting one. It is characterised by insomnia, anxiety,
loss of appetite and of body-weight, tremor, perspiration,
tinnitus, and perceptual disturbances. Some symptoms may
be similar to the original complaint and encourage further
prescribing; some symptoms may continue for weeks or
months after stopping benzodiazepines.
Benzodiazepine withdrawal should be flexible and carried
out at a reduction rate that is tolerable for the patient. The
rate should depend on the initial dose of benzodiazepine,
duration of use, and the patient’s clinical response. Short-
term users of benzodiazepines (2–4 weeks only) can usually
taper off within 2–4 weeks. However, long-term users should
be withdrawn over a much longer period of several months
or more.
A suggested protocol for withdrawal for prescribed long-
term benzodiazepine patients is as follows:
. Transfer patient stepwise, one dose at a time over about a
week, to an equivalent daily dose of diazepam preferably
taken at night.
. Reduce diazepam dose, usually by 1–2 mg every 2–
4 weeks (in patients taking high doses of benzodiazepines,
initially it may be appropriate to reduce the dose by up to
one-tenth every 1–2 weeks). If uncomfortable withdrawal
symptoms occur, maintain this dose until symptoms
lessen.
. Reduce diazepam dose further, if necessary in smaller
steps; steps of 500 micrograms may be appropriate towards
the end of withdrawal. Then stop completely.
. For long-term patients, the period needed for complete
withdrawal may vary from several months to a year or
more.
Approximate equivalent doses, diazepam 5 mg
: alprazolam 250 micrograms
: clobazam 10 mg
: clonazepam 250 micrograms
: flurazepam 7.5–15 mg
: chlordiazepoxide 12.5 mg
: loprazolam 0.5–1 mg
: lorazepam 500 micrograms
: lormetazepam 0.5–1 mg
: nitrazepam 5 mg
: oxazepam 10 mg
: temazepam 10 mg
Withdrawal symptoms for long-term users usually resolve
within 6–18 months of the last dose. Some patients will
recover more quickly, others may take longer. The addition
of beta-blockers, antidepressants and antipsychotics should
be avoided where possible.
Counselling can be of considerable help both during and
after the taper.
Hypnotics
Before a hypnotic is prescribed the cause of the insomnia
should be established and, where possible, underlying
factors should be treated. However, it should be noted that
some patients have unrealistic sleep expectations, and
others understate their alcohol consumption which is often
the cause of the insomnia. Short-acting hypnotics are
preferable in patients with sleep onset insomnia, when
sedation the following day is undesirable, or when
prescribing for elderly patients. Long-acting hypnotics are
indicated in patients with poor sleep maintenance (e.g. early
morning waking) that causes daytime effects, when an
anxiolytic effect is needed during the day, or when sedation
the following day is acceptable.
Transient insomnia may occur in those who normally sleep
well and may be due to extraneous factors such as noise,
shift work, and jet lag. If a hypnotic is indicated one that is
rapidly eliminated should be chosen, and only one or two
doses should be given.
Short-term insomnia is usually related to an emotional
problem or serious medical illness. It may last for a few
weeks and may recur; a hypnotic can be useful but should
not be given for more than three weeks (preferably only one
week). Intermittent use is desirable with omission of some
doses. A short-acting drug is usually appropriate.
Chronic insomnia is rarely benefited by hypnotics and is
sometimes due to mild dependence caused by injudicious
prescribing of hypnotics. Psychiatric disorders such as
anxiety, depression, and abuse of drugs and alcohol are
common causes. Sleep disturbance is very common in
depressive illness and early wakening is often a useful
pointer. The underlying psychiatric complaint should be
treated, adapting the drug regimen to alleviate insomnia. For
example, clomipramine hydrochloride p. 391 or mirtazapine
p. 389 prescribed for depression will also help to promote
sleep if taken at night. Other causes of insomnia include
daytime cat-napping and physical causes such as pain,
pruritus, and dyspnoea.
Hypnotics should not be prescribed indiscriminately and
routine prescribing is undesirable. They should be reserved
for short courses in the acutely distressed. Tolerance to their
effects develops within 3 to 14 days of continuous use and
long-term efficacy cannot be assured. A major drawback of
long-term use is that withdrawal can cause rebound
insomnia and a withdrawal syndrome.
Where prolonged administration is unavoidable hypnotics
should be discontinued as soon as feasible and the patient
warned that sleep may be disturbed for a few days before
normal rhythm is re-established; broken sleep with vivid
dreams may persist for several weeks.
Elderly
Benzodiazepines and the Z–drugs should be avoided in the
Nervous system
elderly, because the elderly are at greater risk of becoming
ataxic and confused, leading to falls and injury.
Dental patients
Some anxious patients may benefit from the use of hypnotics
during dental procedures such as temazepam p. 509 or
diazepam p. 360. Temazepam is preferred when it is
important to minimise any residual effect the following day.
Benzodiazepines
Benzodiazepines used as hypnotics include nitrazepam
p. 509 and flurazepam p. 508 which have a prolonged action
and may give rise to residual effects on the following day;
repeated doses tend to be cumulative.
Loprazolam p. 508, lormetazepam p. 509, and temazepam
act for a shorter time and they have little or no hangover
effect. Withdrawal phenomena are more common with the
short-acting benzodiazepines.
If insomnia is associated with daytime anxiety then the
use of a long-acting benzodiazepine anxiolytic such as
diazepam given as a single dose at night may effectively treat
both symptoms.
Zolpidem, and zopiclone
Zolpidem tartrate p. 512 and zopiclone p. 512 are non-
benzodiazepine hypnotics (sometimes referred to as Z-
drugs), but they act at the benzodiazepine receptor. They are
not licensed for long-term use; dependence has been
reported in a small number of patients. Both zolpidem
tartrate and zopiclone have a short duration of action.
Chloral and derivatives
There is no convincing evidence that they are particularly
useful in the elderly and their role as hypnotics is now very
limited.
Clomethiazole
Clomethiazole p. 511 may be a useful hypnotic for elderly
patients because of its freedom from hangover but, as with
all hypnotics, routine administration is undesirable and
dependence occurs.
Antihistamines
Some antihistamines such as promethazine hydrochloride
p. 301 are on sale to the public for occasional insomnia; their
prolonged duration of action can often cause drowsiness the
following day. The sedative effect of antihistamines may
diminish after a few days of continued treatment;
antihistamines are associated with headache, psychomotor
impairment and antimuscarinic effects.
Alcohol
Alcohol is a poor hypnotic because the diuretic action
interferes with sleep during the latter part of the night.
Alcohol also disturbs sleep patterns, and so can worsen sleep
disorders.
Melatonin
Melatonin p. 511 is a pineal hormone; it is licensed for the
short-term treatment of insomnia in adults over 55 years;
and for the short-term treatment of jet-lag in adults.
Anxiolytics
Benzodiazepine anxiolytics can be effective in alleviating
anxiety states. Although these drugs are sometimes
prescribed for stress-related symptoms, unhappiness, or
minor physical disease, their use in such conditions is
inappropriate. Benzodiazepine anxiolytics should not be
used as sole treatment for chronic anxiety, and they are not
appropriate for treating depression or chronic psychosis. In
bereavement, psychological adjustment may be inhibited by
benzodiazepines.
Anxiolytic benzodiazepine treatment should be limited to
the lowest possible dose for the shortest possible time.
Dependence is particularly likely in patients with a history of
alcohol or drug abuse and in patients with marked
personality disorders.
Nervous system
Some antidepressant drugs are licensed for use in anxiety
and related disorders. Some antipsychotic drugs, in low
doses, are also sometimes used in severe anxiety for their
sedative action, but long-term use should be avoided
because of the risk of adverse effects. The use of
antihistamines (e.g. hydroxyzine hydrochloride p. 299) for
their sedative effect in anxiety is not appropriate.
Beta-adrenoceptor blocking drugs do not affect
psychological symptoms of anxiety, such as worry, tension,
and fear, but they do reduce autonomic symptoms, such as
palpitation and tremor; they do not reduce non-autonomic
symptoms, such as muscle tension. Beta-blockers are
therefore indicated for patients with predominantly somatic
symptoms; this, in turn, may prevent the onset of worry and
fear.
Benzodiazepines
Benzodiazepines are indicated for the short-term relief of
severe anxiety; long-term use should be avoided. Diazepam,
alprazolam p. 360, chlordiazepoxide hydrochloride p. 360,
and clobazam p. 353 have a sustained action. Shorter-acting
compounds such as lorazepam p. 355 and oxazepam p. 362
may be preferred in patients with hepatic impairment but
they carry a greater risk of withdrawal symptoms.
In panic disorders (with or without agoraphobia) resistant
to antidepressant therapy, a benzodiazepine may be used;
alternatively, a benzodiazepine may be used as short-term
adjunctive therapy at the start of antidepressant treatment
to prevent the initial worsening of symptoms.
Diazepam or lorazepam are very occasionally administered
intravenously for the control of panic attacks. This route is
the most rapid but the procedure is not without risk and
should be used only when alternative measures have failed.
The intramuscular route has no advantage over the oral
route.
Buspirone
Buspirone hydrochloride p. 358 is thought to act at specific
serotonin (5HT1A) receptors. Response to treatment may
take up to 2 weeks. It does not alleviate the symptoms of
benzodiazepine withdrawal. Therefore a patient taking a
benzodiazepine still needs to have the benzodiazepine
withdrawn gradually; it is advisable to do this before starting
buspirone hydrochloride. The dependence and abuse
potential of buspirone hydrochloride is low; it is, however,
licensed for short-term use only (but specialists occasionally
use it for several months).
Meprobamate
Meprobamate p. 363 is less effective than the
benzodiazepines, more hazardous in overdosage, and can
also induce dependence. It is not recommended.
Barbiturates
The intermediate-acting barbiturates have a place only in
the treatment of severe intractable insomnia in patients
already taking barbiturates; they should be avoided in the
elderly. Intermediate-acting barbiturate preparations
containing amobarbital sodium, butobarbital, and
secobarbital sodium are available on a named patient basis.
The long-acting barbiturate phenobarbital is still
sometimes of value in epilepsy but its use as a sedative is
unjustified.
The very short-acting barbiturate thiopental sodium p. 354
is used in anaesthesia.
Increased hostility and aggression after barbiturates and
alcohol usually indicates intoxication.
HYPNOTICS, SEDATIVES AND
ANXIOLYTICS › BENZODIAZEPINES
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PDF pages 528, 529, 530
