Pharmacologic approach to insomnia treatment

Over-the-Counter Products: A variety of over-the-counter products are promoted as sleep aids, but these drugs often have many side effects and may not provide effective and sustained relief. They include herbal remedies or antihistamines, which induce sleep, but also may lead to daytime drowsiness, blurred vision, and dry mouth. Very little evidence supports the efficacy of these sleep aids, despite their widespread use.

Prescription Sleep Medications: Until the 1960s, barbiturates, such as phenobarbital, were widely used as sedatives, despite their association with such dangerous side effects as addiction, tolerance, and overdosage.

In the 1960s, benzodiazepines (also known as benzodiazepine receptor agonists) were introduced and soon became the mainstay of pharmacologic treatment. Some benzodiazepines in use today include flurazepam, triazolam, and temazepam.

Benzodiazepines are central nervous system depressants that work by enhancing the actions of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at its receptor. GABA is believed to be one of the factors that help promote sleep, and also is involved in cognitive, memory, and psychomotor functions. Because benzodiazepines bind nonspecifically to GABA receptors, they actually may be more active in reducing anxiety, inducing muscle relaxation, and inhibiting convulsions than in promoting sleep. Their side effects, such as memory loss, rebound insomnia (sleep gets worse than before the treatment), and drug dependence, may make them inappropriate for treatment of insomnia.

In the early 1990s, new hypnotics of nonbenzodiazepines (or nonbenzodiazepine receptor agonists) were introduced that target only certain receptor subtypes of the GABA complex. These drugs, which include zolpidem and zopiclone, have the advantage of being much shorter acting compounds with less likelihood for daytime sleepiness or impairment of memory. Unfortunately, they still have some side effects, including rebound insomnia, dependence, drowsiness, dizziness, lightheadedness and difficulty with coordination.

However, one medication for the treatment of primary insomnia, prolonged-release melatonin, recently received approval from the European Medicines Agency (EMEA). Based on published clinical reports, this medication has demonstrated safety and efficacy of nightly use, and helps people fall asleep, wake up refreshed in the morning and improves quality of sleep, without impairing your sleep architecture.

Unlike other prescription sleep aids, this prolonged-release melatonin is thought to work by selectively affecting melatonin receptors (neurons) in the body clock in the suprachiasmatic nucleus (SCN), a part of the brain that functions to regulate times for sleep and times for optimal alertness or wakefulness. This contrasts with other hypnotic medications that work by binding to GABA receptors, which reduce central nervous system (CNS) activity.

Prolonged-release melatonin has not shown evidence for dependence or abuse. Only few side effects such as asthenia, headache or back pain have been reported. However, the rate in comparison to placebo was so benign, that there are no obvious differences in safety parameters between the active treatment and the placebo group.