Sleeping Pills to Treat Insomnia

Circadin.com April 27, 2017

The primary goals of treating insomnia are to reduce any related daytime impairments, improve daytime functioning, reduce stress, improve sleep quality and improve sleep time. A well-planned treatment that includes sleeping pills, in addition to well-defined sleep habits and behaviours, can help achieve these goals.
There are several medication classes that are used to treat insomnia:

Prolonged-release melatonin

Melatonin is a natural hormone, produced in the brain, that regulates sleep and signals darkness in humans1 2. As people age the frequency and severity of insomnia increases and the secretion of melatonin decreases3 4

Melatonin as a sleep medication is available in prolonged-release form. After consumption it produces levels of melatonin over the following 8-10 hours to mimic the body’s natural melatonin levels5.

Prolonged-release melatonin is used for short-term treatment of primary insomnia in patients aged 55 years or over6. The recommended dose of prolonged-release melatonin is 2mg once daily, swallowed whole after food 1-2 hours before bedtime6. Alcohol consumption should be avoided as it may decrease the effectiveness of this sleeping pill6.

Effectiveness of prolonged-release melatonin

Prolonged-release melatonin has been shown to effectively deliver quality and restorative sleep2 7.

British guidelines recommend that when a hypnotic is indicated in patients over 55, prolonged-release melatonin should be tried first1.
In both short term (3 weeks) and long term studies (6 months) prolonged-release melatonin has been clinically shown to:

  • Improve quality of sleep2 5 7 8

  • Decrease sleep latency2 8

  • Improve morning alertness2 5 7

  • Increase total sleep time in patients over 55 years9

Adverse events of prolonged-release melatonin

Several researches suggest little difference between prolonged-release melatonin and placebo in the type and rate of adverse events experienced6 2 5.
Common adverse events reported include headache, nasopharyngitis, back pain and arthalgia6.
Prolonged-release melatonin does not negatively impact sleep architecture or impair daytime motor performance which instead is better than placebo8. Prolonged-release melatonin has not been associated with suppression of natural melatonin production10.

Importantly, stopping use of prolonged-release melatonin has not been associated with rebound insomnia or withdrawal effects8 even when used for 6 months9.

Benzodiazepines

Benzodiazepines, as a medication class, are a commonly prescribed sleeping pills for insomnia in many countries11. They act selectively on receptors in the central nervous system, resulting in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects12.

In general, benzodiazepines will promote sleep when taken at night13. Benzodiazepines should be given for short-term use only (2-4 weeks). They also should be part of a broader treatment plan, not as sole treatment.

Effectiveness of benzodiazepines

Benzodiazepines have been shown to be effective in promoting and maintaining sleep when compared with placebo11 14.

When compared to placebo, benzodiazepines effectively reduced sleep latency by between 4.2 and 23.7 minutes and improved total sleep duration by between 48.4 and 61.8 minutes15.

Adverse effects of benzodiazepines

The most common adverse effects of benzodiazepine use are drowsiness, headache, dizziness, nausea and fatigue16. Its use is associated with an increased risk of adverse cognitive events (such as confusion or memory loss), adverse psychomotor events (such as dizziness or loss of balance) and daytime fatigue in older patients17 18. Specifically, use of this medication class is more likely than placebo to be associated with complaints of daytime drowsiness and reports of cognitive impairment15.

blisters of sleeping pills

Benzodiazepine use is also associated with a greater rate of falls and motor vehicle accidents than placebo18 19.

Benzodiazepine use can have a negative impact on sleep architecture. Whilst sleep duration is increased by benzodiazepines, the time spent in deep sleep and REM sleep is actually decreased11.

In general, elderly patients show greater cognitive impairment and sedation after taking benzodiazepines15. Additionally, elderly patients are also at greater risk of falls, respiratory depression and short-term memory impairment. The increased risk of adverse events in patients aged over 60 has raised questions about whether the benefits outweigh the risks for this age group18.

Long-term use of benzodiazepines should be avoided as it may result in tolerance, dependence and addiction20 21 22. Withdrawal is another significant adverse effect, more likely to occur following use of short-acting pills, particularly those who “peak” quickly. The use of long acting benzodiazepine may reduce and give better control of withdrawal symptoms23. Rebound effects after withdrawal from benzodiazepines are believed to contribute to their chronic use and may also increase the risk of dependence24.

Z-drugs

Zolpidem and zopiclone are newer generation hypnotics commonly referred to as z-drugs. Z-drugs are compounds that are structurally different from benzodiazepines, however work through the same receptor complex25.

Zolpidem is a fast acting sleeping pill, recommended to be taken at a dose of 10mg at night, immediately before retiring to bed26. In elderly patients the dose should be reduced to 5mg and not be exceeded26. Zolpidem is also available in a controlled-release formulation. It is recommended that patients take it at night immediately before retiring, at a dose of 12.5mg for adults and 6.25mg for elderly patients27.

Zopiclone is a sleep medication recommended to be taken at a dose of 7.5mg at night, shortly before retiring to bed28. Elderly patients should be initiated on 3.75mg. In case the starting dose does not offer adequate therapeutic effect, it should be increased to a maximum of 7.5mg28.

Effectiveness of z-drugs

Z-drugs are effective in improving multiple sleep measurements. These include time to fall asleep, increasing total sleep time, improving sleep efficiency, reducing duration of night awakenings and enhancing sleep quality1.
Z-drugs alter the sleep architecture significantly35. Furthermore, there is no convincing evidence showing significant differences in the efficacy or safety of zolpidem and zopiclone compared with benzodiazepines for insomnia.

Adverse effects of z-drugs

Common adverse effects of z-drugs include diarrhoea, drowsiness, headache, fatigue, dry mouth and taste disturbance (bitterness)27 28.
Indirect comparisons suggest that z-drugs may pose a lower risk of harm than benzodiazepines, however z-drugs are not without risk16 29. Next-day driving simulation experiments have shown that previous dosing with zopiclone increased the number of collisions compared to placebo, whilst zolpidem did not differ from placebo30. In contrast, a recent survey of road traffic accidents found an association between zolpidem use and increased risk of being responsible for a traffic accident, whilst there was no association found with use of zopiclone31. Note, the driving risk associated with zolpidem appeared to be concentrated amongst people who used more than one tablet per day31.

Accumulated data have associated z-drugs with reported hallucinations and bizarre parasomnias. These include sleep-walking, sleep-driving, sleep-sex and other parasomnias. This phenomenon has been frequently reported in the media, especially regarding zolpidem29.

Patients using these sleeping pills should be aware of the potential adverse effects. They should be advised to avoid alcohol (which is contraindicated)26. The medication should be taken once in bed, not on the way to bed. Simple changes to the home environment, such as locking doors can reduce the risk of harm from sedation, disinhibition and confusion. This is crucial in case of patients with a psychiatric illness that may lead them to suicide or are taking multiple psychoactive drugs29.

Other classes

Antidepressants

Antidepressants with sedating effects are commonly used for managing insomnia25 32. The popularity of using antidepressants as sleeping aids in treating insomnia is not supported by convincing data25 33 and has no strong evidence base but instead is largely based on clinical experience. When used for insomnia they are commonly used at low doses1.

Antidepressants have longer-lasting left-over effects than traditional hypnotics and therefore their use needs to managed with appropriate counselling1. There is no evidence of superiority or a better benefit/risk ratio of antidepressants over benzodiazepines or z-drugs33.

Antipsychotics

Atypical antipsychotics are indicated for the treatment of psychosis such as schizophrenia, and are sometimes used in insomnia despite very limited clinical evidence1.

The common adverse effects of atypical antipsychotics are well documented, even at low doses. They include weight gain, metabolic syndrome, extrapyramidal symptoms and risk of movement disorders such as tardive dyskinesia1.

OTC antihistamines

Diphenhydramine and doxylamine are over-the-counter sedating antihistamines that are indicated for the short term management of insomnia, and are not to be used for more than 10 consecutive days. Antihistamines promote sleep by reducing arousal. There is a limited evidence base demonstrating that sedating antihistamines have modest benefits in mild insomnia1 34.

Adverse effects include daytime sedation, psychomotor impairment and anticholinergic effects. The use of over-the-counter sedative antihistamines by elderly patients is not recommended.

Which sleeping pills are right for you?

Please consult with your doctor, or other qualified healthcare professional before using any of the above pills.

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