Most people have sleep difficulties at some point in their life. While this is transient for some, for others it can be long term. For those who experience insomnia occasionally, over-the-counter sleep aids may be enough, but those who experience it more often may need to get a prescription sleep aid.
'Traditional' Sleep Aids
Many sleep mechanisms involve a brain neurochemical gamma-aminobutyric acid, or GABA, which works by activating receptors on nerve cells. The GABA-A receptor is made up of different subunits; most sleep aids work by activating the alpha subunit. There are six types of alpha subunit, with slightly differing actions including sedation, anti-anxiety effects, muscle relaxation and memory impairment. The most often prescribed 'traditional' sleep aids are benzodiazepines, including estazolam and temazepam. These work at all alpha subunit types, so they can help with sleep, but they can also cause next-day physical slowing and memory problems. Individual benzodiazepines have different properties; some last a couple of hours and are used for only a few days, others work for a longer time and can be taken for up to 30 days. Tolerance to benzodiazepines can build up over time, meaning higher doses are needed to gain an effect. There may also be withdrawal effects, including anxiety and increased heart rate, according to "Stahl's Essential Psychopharmacology;" by Stephen M. Stahl, and "Med Clin N Am;" by Shannon S. Sullivan.
Next-Generation Sleep Aids
Newer, 'next generation' sleep aids include zaleplon, zolpidem and eszopiclone. These mostly work only at the alpha-1 subunit---that primarily leads to sedation---meaning there are fewer of the side effects of benzodiazepines, according to Sullivan and also reported in the article "Chronic Insomnia," by Michael H. Silber, in The New England Journal of Medicine in August 2005.
Zaleplon, or Sonata, effects last fewer than 4 hours so it is best for people with problems getting to sleep or who wake up at night. Zolpidem, or Ambien/Ambien-CR, works for a longer time---6 to 8 hours---so it is good for keeping someone asleep. These sleep aids are for short-term treatment of 7 to 10 days. Eszopiclone, or Lunesta, is also good for keeping someone asleep and is approved for longer use of more than 10 nights, according to fact sheets about the drugs.
Tolerance and withdrawal are rare with next-generation sleep aids, and side effects occur in a low percentage of people. All of them may cause headache and memory problems, with Sonata also causing abdominal pain, Ambien causing nightmares, sleep-related eating and dizziness, and Lunesta causing anxiety, abnormal dreams and a lingering unpleasant taste
Ramelteon, or Rozerem, acts at the same receptors as the neurochemical melatonin, which is involved in the signal to sleep. It is short acting, so it is only useful for people who have problems getting to sleep. Its effect may take a number of days to build up, but it has no withdrawal or tolerance problems and can be used long term. Rare side effects include somnolence, nausea and headache, according to fact sheets about the drugs.
Other Sleep Aids
There are other drugs prescribed for insomnia although they are not primarily for this problem. For instance, the antidepressant trazodone activates the GABA-A alpha-1 subunit as well as a histamine receptor, which is how many over-the-counter sleep aids work. Side effects with trazodone include constipation, hypotension and light-headedness. The antipsychotic quetiapine also has actions at histamine receptors. Their main use is for insomnia associated with psychiatric disorders, and side effects may include periodic limb movements, hyperglycemia, agitation and liver problems.
References
- "Stahl's Essential Psychopharmacology;" Stephen M. Stahl; 2008
- "Med Clin N Am;" Insomnia Pharmacology; Shannon S. Sullivan; 2010
- "The New England Journal of Medicine;" Chronic Insomnia; Michael H. Silber; August 2005
- Mendelson WB et al in Kryger MH et al. Principles and Practice of Sleep Medicine. Elsevier Saunders, Philadelphia. 2005
- Sonata (zaleplon) data sheet. 2004
