Sleep disorders may be simple to resolve through various non-pharmacological therapies that include learning to relax prior to sleep through relaxation techniques and a process of biofeedback, or through other means such as cognitive therapy (addressing dysfunctional cognitive processes to help promote sleep), stimulus-control therapy (to relieve apprehension around bedtime), and sleep restriction therapy (improve sleep efficiency by reducing the time spent in bed when not asleep). In terms of treating insomnia, the latter two therapies are the most effective. Another alternative in combating sleep disorders, in general, is the education of individuals regarding good sleep hygiene (how a good diet, healthy exercise, and an appropriate environment can promote sleep). However, this is perhaps the least effective of these non-pharmacological therapies, but may be useful in combination with the others.
In addition to these behavioural and cognitive therapies, there are various alternative and herbal remedies available, such as medicinal herbs (e.g., Valeriana officinalis), dietary supplements (e.g., Piper methysticum), camomile tea, or precursors of serotonin and melatonin (5- hydroxytryptophan) which, via an increase in serotonin levels, may boost melatonin levels. However, these alternative treatments and herbal remedies have not been formally regulated and the effect of long-term treatment with these agents has not been elucidated.
Where the sleep disorder is of a more chronic nature, and behavioural and cognitive therapies have been unsuccessful, pharmacological intervention with an appropriate hypnotic may be required. Traditionally, benzodiazepines (e.g., lormetazepam, triazolam, temazepam, brotizolam, nitrazepam, and flunitrazepam) have been prescribed for this purpose and have demonstrated efficacy in the treatment of insomnia, albeit on a quantitative (amount of sleep) rather than a qualitative (getting a good nights sleep) level. However, their broad-range activity at target receptor sites has resulted in multiple side effects. Furthermore, the benzodiazepines have been associated with addiction potential, psychomotor and cognitive impairment, and memory problems. To counteract this, the non-benzodiazepines – the ‘z’-drugs, e.g., zolpidem, zaleplon, zopiclone and eszopiclone – were developed with a more selective mode of action, and a more favourable safety profile as a result, whilst maintaining efficacy. However, side effects are still evident with ‘z’-drug treatment and the potential for addiction, abuse, etc, as seen with the benzodiazepines, remains.
Melatonin receptor agonists (e.g., Circadin®) have been shown to be effective in sleep disorders and hence, this agent is considered as a promising new agent in this field. Antidepressants and antihistamines have also been use in the treatment of sleep disorders, but are usually not indicated for such use and can be accompanied with harmful and unwanted side effects.
As a result, there is currently a significant unmet need for the ‘ideal’ sleep drug, particularly one which will prove effective and safe for long-term treatment.
The current guidelines recommend that pharmacological sleep agents be prescribed for a maximum period of 4 weeks, due to the risk of abuse and dependency. Newer agents are likely to provide improvements with regard to next-day residual effects and abuse liability, such that further development in these areas may see an alleviation of these restrictions and a movement towards more long-term therapy with sleep agents.