insomnia in practice

Question 1

what is incomnia?

Answer 1

nsomnia is typically characterised by

unsatisfactory sleep

Question 2

how is insomnia characterised?

Answer 2

•Sleep-onset insomnia (more common in 
younger pts) 
•Frequent nocturnal awakening (more 
common in older pts)
•Early waking 
And  poor daytime functioning with affected 
mood.

Question 3

what are some of the detrimental effects of insomnia?

Answer 3

decrease in QOL
depression risk
diabetes risk
HPT risk
impaired function
dec in productivity absenteeism accidents

Question 4

how would you assess insomnia?

Answer 4

Patient questioning
–Sleep habits?
–Sleep scheduling?
–Intake of substances 
that can disturb 
sleep?

Question 5

how would you manage short-term insomnia? ie less than 3 months

Answer 5

•Manage any identifiable causes where possible, sleep
hygiene
•Hypnotic considered if daytime impairment severe
•Lowest dose for shortest duration (not more than 2
weeks)
•If symptoms persist, refer for CBT
•Short acting benzodiazepine or Z drug

Question 6

why are diazepam, nitrazepam and flurazepam not recommended for short term treatment of insomnia?

Answer 6

because their long half-life commonly gives
rise to next-day residual effects, and repeated doses tend
to be cumulative.

Question 7

how do you treat long-term insomnia?

Answer 7

•Manage any underlying cause where possible; sleep hygiene
•Refer to psychological services (IAPT) for a cognitive or
behavioural treatment

Question 8

when is pharmacological treatment recommended for long term patients with insomnia?

Answer 8

–For people with severe symptoms or an acute exacerbation of persistent insomnia a short course (2 weeks, occasionally 4) of a hypnotic drug may be considered for immediate relief of
symptoms
–For people over 55years of age with persistent insomnia, consider treatment with a modified-release melatonin.
–Sleep clinics if insomnia persists despite primary care management

Question 9

what would be non-drug treatment for insomnia?

Answer 9

 Cognitive Behavioural Therapy (CBT) – BAP 1st line

 Good “sleep hygiene”

Question 10

why is pharmacokinetics important in insomnia?

Answer 10

•The faster a drug enters the brain the sooner 
sleep is induced
–Risk if too quickly? 
•Duration of action?
–Linked to ease of waking
–Hangover effects

Question 11

what is the rationale for the use of z drugs?

Answer 11

shorter half life with minimal hangover effect

Question 12

how would bioavailability influence the choice of drug?

Answer 12

–Formulation e.g. temazepam tablets have a poorer
bioavailability and slower absorption and a longer
presence in the body than previous gel formulations.

Question 13

what are the individual factors to consider when treating insomnia?

Answer 13

–Hangover effects vary significantly between patients
–Sleep onset insomnia shorter acting drug may be best
e.g. zolpidem, melatonin
–Waking through the night- slightly longer duration of
action e.g. zopiclone

Question 14

what do the traditional benzodiazepine drugs for insomnia act on?

Answer 14

he alpha-1, 2,3 and 5 
subtypes
•Zolpidem targets alpha-1 
subtype preferentially
•Eszopiclone targets alpha-3 
subtype preferentially

Question 15

what do benzos and z drugs enhance the effects of?

Answer 15

enhance the effects of

GABA at the GABAA receptor.

Question 16

what antihistamine that crosses the BBB is used to promote sleep OTC?

Answer 16

diphenhydramine

Question 17

what do orexins do?

Answer 17

antagonists of OR1 and OR2
(Newer agents) promote sleep e.g.
Suvorexant (not available in Europe)

Question 18

when is hypotnotics most beneficial?

Answer 18

High quality evidence for efficacy of hypnotics in
short-term insomnia (≤4 wks) - but consider
adverse effects

Question 19

why is long term pharmacological treatment not recommened?

Answer 19

–Side effects/risks
–Conflicting evidence of effectiveness
–Intermittent dosing?

Question 20

how do NICE recommend that hypnotics should be prescribed?

Answer 20

prescribe the cheapest drug, taking into
account the daily dose required and the cost for
each dose.

Question 21

when should hypnotics be changed?

Answer 21

–Treatment should only be changed from one of these
hypnotics to another if side effects occur that are
directly related to the medicine.

Question 22

what if treatment of hypnotics does not work?

Answer 22

If treatment with one of these hypnotic medicines
does not work, the doctor should not prescribe one
of the others.

Question 23

when should benzodiazepines be given?

Answer 23

consider a short course of a hypnotic drug only if daytime
impairment is severe.
•If no response to a hypnotic do not prescribe another.

Question 24

what is a short-/long acting benzo?

Answer 24

Short-acting
•Temazepam, loprazolam, lormetazepam, lorazepam
Long acting
•Nitrazepam, flurazepam, diazepam

Question 25

what are some of the ADRs with benzos?

Answer 25

tolerance and dependence, cognitive and psychomotor impairment, depression, emotional blunting, paradoxical anxiety, aggression, hyperactivity, fall risk, inc risk of road accidents

Question 26

what are the key interactions that benzodiazepines have?

Answer 26

alcohol/opiates- lethal sedation
centrally acting drugs- cns depression
antihpt, vasodilatiors and diuretics- hypotensive effect
CYP450 inhibitors- inc benzo effects
CYP450 inducers- decrease benzo effects
phenytoin- alt phenytoin levels

Question 27

what do the different z drugs treat?

Answer 27

Zaleplon 1 hour Difficulty getting to sleep. Max 2 weeks

Zolpidem 2.5 hours Debilitating or causing distress. Max. 4
weeks

Zopiclone 3.5-6.5 hours Debilitating or causing distress. Max. 2-3
weeks

Question 28

what are the ADRs of z-zdrugs?

Answer 28

GI disturbances, paradoxical effects, dizziness, drowsiness, dry mouth, confusion, hallucinations, nightmares, perceptual disturbances

Question 29

what are the key interactions with Z drugs?

Answer 29

alcohol and opioids- can induce lethal sedation
Centrally acting drugs- CNS depression
CYP450 inhibitors- enhance z drugs effects
inducers- can accelerate hepatic elimiation of Z drugs
phenytoin- alt levels of phenytoin

Question 30

what is melatonin?

Answer 30

•Pineal hormone involved in the 
regulation of circadian rhythm. 
•Production of melatonin declines with 
age; levels lower in middle-aged/elderly 
people who have insomnia.

Question 31

what has prolonged release melatonin shown to improve?

Answer 31

shown to improve sleep onset

latency and quality in patients over 55 yrs.

Question 32

who is melatonin licensed for? what is the dose?

Answer 32

Licensed for short-term treatment of insomnia in adults over 55
years.
•Dose: 2mg once daily, taken 1-2 hours before bedtime for up to
13 weeks (recommended initial duration is 3 wks).

Question 33

what are the adverse effects of melatonin?

Answer 33

headache, dizziness, nausea, drowsiness,

falls risk.

Question 34

what should you avoid on melatonin?

Answer 34

Avoid alcohol- less effective, plus additional CNS depressant
effects

Question 35

what are some other drugs used for insomnia?

Answer 35

edating antidepressants (not generally recommended):
–If co-existent mood disorder, might consider use of
antidepressants
–Not generally recommended but low doses (sub-therapeutic
for depression) of sedating tricyclics, particularly amitriptyline
(10-25mg at night) are commonly used in UK for long periods

Question 36

how should you discontinue treatment?

Answer 36

Discontinuation of hypnotics should be based on slowly
tapering down medication.
•CBT during taper can improve outcome

Question 37

what are the usual effects during the withdrawl periods ?

Answer 37

Temporary worsening of sleep, usually taking longer to fall
asleep is reported during the withdrawal period for most
GABAergic agents

Question 38

what are the symptoms of withdrawl?

Answer 38

•Anxiety/agitation (most 
common)
•Insomnia
•Dizziness
•Headache
•Abnormalities of 
perception
•Tremor, sweating, tinnitus, 
nausea, vomiting
•Occasionally, psychosis or 
convulsions

Question 39

how long does it take to withdraw?

Answer 39

Gradually withdraw over 4-8 weeks after long term use, can take up to 1 year

Question 40

how should you taper the dose?

Answer 40

–such as 5–10% reduction every 1–2 weeks, or an eighth of the dose fortnightly, with a slower reduction at lower doses, and titrated according to the severity of withdrawal
symptoms.

Question 41

who is switchig to diazepam recommended for?

Answer 41

•Short-acting potent benzodiazepines (alprazolam and lorazepam).
•Preparations that do not easily allow for small reductions in dose (alprazolam, flurazepam, loprazolam and lormetazepam).
•Temazepam or nitrazepam who choose to withdraw from diazepam after discussing the advantages and disadvantages.
•Difficulty withdrawing directly from temazepam, nitrazepam, or z-drugs, due to a high degree of dependency (associated with long
duration of treatment, high doses, and a history of anxiety
problems).

Question 42

is exact sub dose possible for diazepam?

Answer 42

Exact dose substitution is not possible
Switching to diazepam is best carried out gradually, usually in a stepwise fashion.
–Consider making the first switch in the night-time dose to avoid daytime sedation.

Question 43

what is some additional patient advice to give to the patient?

Answer 43

•Sleep hygiene
•Hypnotics: Advise the person not to drive if they
feel sleepy (although it is not necessary to inform
the Driver and Vehicle Licensing Agency [DVLA]
unless a primary sleep disorder is confirmed).
•Driving on Benzodiazepines and UK Law
•Duration of treatment! Tolerance and
dependence
•Alcohol and illicit drugs