principles of pharmacological management of insomnia

Last edited 05/2020

pharmacological management of insomnia

Pharmacotherapy should be considered as an adjunctive therapy to non pharmacological methods.

  • hypnotic drugs are commonly used to manage insomnia
  • minimum dose required should be used for the minimum duration possible

Hypnotics are indicated in patients whose normal daily lifestyle is disturbed as a result of severe insomnia

  • drug treatment can be divided broadly into
    • benzodiazepine hypnotics
      • short acting drugs - loprazolam, lorazepam, lormetazepam and temazepam
      • long acting drugs - diazepam, nitrazepam, and flurazepam are not recommended because it may cause next day residual effect (1)
      • contraindicated in people with severe respiratory diseases (1)
      • adverse effects - hangover, dizziness, hypotension and respiratory depression (2)
      • rebound insomnia may occur (1)
    • nonbenzodiazepine hypnotics e.g.- zaleplon, zolpidem and zopiclone (the Z-drugs)
    • miscellaneous sleep promoting agents (1)
      • melatonin - used to treat circadian rhythm sleep disorders
      • antidepressants (amitriptyline, doxepin, trazodone) - is useful in patients who have insomnia and concomitant depression (3)
      • antihistamines - the efficacy of the drug has not been proven and it may have a minimal effect in inducing sleep (3,4)
  • NICE suggest that, with respect to insomnia in adults, because of the lack of compelling evidence to distinguish between zaleplon, zolpidem, zopiclone or the shorter-acting benzodiazepine hypnotics, the drug with the lowest purchase cost (taking into account daily required dose and product price per dose) should be prescribed (5)

Occasionally short-term treatment with a hypnotic may be appropriate e.g. for transient insomnia, such as jet-lag

  • hypnotic drugs should, in general, be given only for very short periods (ideally, intermittently and for no more than a few days) to alleviate acute distressing insomnia caused by short-lasting events, illnesses or upsets
  • hypnotic drugs should only be given after careful assessment, and after education and appropriate non-drug measures have proved insufficient
  • to minimise residual next-day sedative effects, a shorter-acting drug, given in the lowest effective dose, is a better choice than a longer-acting drug. However, in elderly people, it is safer to avoid hypnotics altogether, wherever possible

Long-term prescribing of hypnotics must be resisted because withdrawal may cause insomnia that is as distressing as the original complaint

  • long-term use of hypnotic drugs has not been proven to be effective for patients with chronic insomnia, and should generally be avoided
    • in such individuals, first-line management should be directed at identifying and treating any underlying cause (such as depression); alongside this, psychological and/or behavioural treatments are a more suitable approach than hypnotic drugs

Also continuation of hypnotic use can be associated with impaired performance during the day, tolerance to the sedative effects and drug dependency (6,7).

Summary points (1)

Drug treatments for short-term treatment of insomnia:

  • Gamma-aminobutyric acid (GABA)-positive allosteric modulators (PAMs) are efficacious for insomnia
    • benzodiazepines, so-called ‘Z drugs’ and barbiturates all enhance the effects of GABA at the GABA alpha receptor (GABA-PAMs)
  • safety concerns (adverse events and carry-over effects) are fewer and less serious in hypnotics with shorter half-lives
  • prolonged release melatonin improves sleep onset latency and quality in patients over 55 years - has no known motor side effects
  • suvorexant is efficacious in insomnia
  • doxepin in very low doses (3 mg and 6 mg) is efficacious in insomnia (Ia)
    • selective antihistamine doxepin (very low dose) is effective in insomnia
    • non-selective histamine antagonists have a limited role in
      psychiatric and primary care practice for the management of insomnia

Using long-term treatment regimes for insomnia (1)

  • insomnia is often long-lasting and is in practice often treated with hypnotics for long periods in clinical practice
  • studies suggest that dependence (tolerance/withdrawal) is not inevitable with hypnotic therapy up to one year with eszopiclone, zolpidem, ramelteon
  • intermittent dosing may reduce the risk of tolerance and dependence

Notes:

  • driving and hypnotic treatment:
    • study evidence has shown that zopiclone or zolpidem double the risk of road traffic accidents compared with people who weren't prescribed hypnotics, similar to the increased risk seen with nitrazepam
    • although there is a common perception that Z-drugs are less likely to have a 'hangover' effect the next day and may reduce the risk of accidents and falls, the clinical evidence to differentiate Z-drugs from benzodiazepines is weak. Patients should be advised that the taking of zolpidem or zopiclone is associated with about double the relative risk of road traffic accidents, and they need to be very cautious about driving the day after taking any hypnotic (6)
  • all currently available drugs appear capable of causing dependence with regular use, and should be treated as such (7)
    • patients should be advised of this risk, and should not be issued with repeat prescriptions without reassessment
    • many long-term users of benzodiazepine hypnotics are able to reduce or stop their use of these medications, with benefit to their health and without detriment to their sleep, if given simple advice and support during dose-tapering
    • a meta-analysis concluded that, in older persons with insomnia short term treatment with sedative hypnotics is twice as likely to produce an adverse effect as improve the quality of sleep (7)

Reference:

Related pages:

mode, speed and duration of action of hypnotics