Soft, drifting on air, light and beautiful...The Luna moth is now associated in everyone's mind with the sleeping medication Lunesta - the result of a brilliant marketing campaign. Who wouldn't be able to sleep, adrift on a blanket of calm, serene night air?
Sleeping medication is frequently prescribed and is big business. Anyone watching TV or reading magazines sees plenty of perfectly coifed, rested-looking individuals smiling as they gently awaken and greet the sunlit morning. In other words, these medicines are being advertised aggressively by the pharmaceutical industry. Properly used they can be very helpful - but there are associated risks and costs.
Medication management is one of the two major approaches to the treatment of insomnia, the other being cognitive behavior therapy, which will be discussed next time. The focus of this post is prescription medications that are used by health care providers to treat insomnia. The use of regulated (over-the-counter) medications and unregulated (herbal, homeopathic, hormonal and dietary) supplements as sleep aids will be discussed in the future.
How do these seemingly magical potions help us to sink into sleep? Current sleeping medications work in a number of different ways, by affecting various brain systems involved with the sleep and wake systems. Each has benefits and potential risks which need to be understood and weighed in any given clinical situation. First, there are medications which are not FDA approved as sleep medications but that physicians may use "off-label" to treat sleep problems. Second, there are FDA-approved insomnia treatment medications.
Indeed, some of the most frequently prescribed medications for insomnia are actually antidepressants used off-label for this purpose. The major ones are trazodone, amitriptyline and mirtazapine. These drugs have complex effects on many neurotransmitters including serotonin, norepinephrine and histamine. These are know as sedating antidepressants and may well help sleep in depressed people but there are few data that show they're effective or safe in non-psychiatric patients. A few of the problems that may occur with these medications include morning "hangover," cardiac arrhythmias, and orthostatic hypotension.
The FDA has approved two types of medication specifically for the treatment of insomnia. These are the benzodiazepine receptor agonists and the melatonin receptor agonists (of which only one drug has been approved to date). The benzodiazepine receptor agonists include the benzodiazepines and the nonbenzodiazepine hypnotics (drugs that promote sleep by affecting the benzodiazepine receptor complex but are structurally unrelated to the benzodiazepines). These drugs work by affecting the GABA receptor complex. GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system. Benzodiazepine receptor agonists may have a general cortical sedating effect but most importantly affect the ventrolateral preoptic nucleus which is involved in the regulation of sleep and wakefulness. Melatonin receptor agonists have an entirely different mode of action and selectively affect melatonin receptors in the suprachiasmatic nucleus which is involved in the regulation of the sleep-wake cycle (circadian or 24 hour rhythms).
The benzodiazepines include such well know drugs such as Valium and Xanax that may be used to promote sleep but also have other medical uses such as the management of anxiety. These medications were introduced in the 1960's and were first recommended for insomnia in the 1970's.
There are five immediate release benzodiazepines approved specifically for treatment of insomnia: ProSom, Dalmane, Dorale, Restoril and Halcion. All of these medications speed sleep onset and increase sleep time and are moderately effective for the treatment of insomnia. There are three immediate release nonbenzodiaepines indicated for the treatment of insomnia: Lunesta, Sonata, and Ambien. There is also a time release version which is designed to help maintain sleep later in the night: Ambien CR. These medications are effective for treatment of insomnia. Based on recent research Lunesta and Ambien CR have been found effective for long term use (more than 6 months). In the past, they were recommended only for short term use, as are the other benzodiazepine receptor agonists.
These medications work rapidly and should be taken only when going to bed. Except for Sonata, which is very rapidly eliminated from the body, all should be taken only if the patient has 7 to 8 hours to spend in bed. They are generally well tolerated, although adverse effects can include day time sleepiness, amnesia for events prior to taking the medication, headache, diarrhea, nausea, and dizziness. A rare effect with potentially significant impact is sleep walking or confused behavior in the hours after taking the medication. All can result in rebound insomnia if suddenly stopped. Medically supervised slow tapering is necessary when discontinuing these medications.
The first FDA approved sleeping medication in several decades that has an entirely new mode of action is Rozerem, a melatonin receptor agonist. This drug affects the melatonin receptors without significant interaction with other neurotransmitter systems. It promotes sleep without causing a sedating effect and because of its targeted activity it has few potential adverse effects. It appears to work by decreasing the arousal generated in the evening by the circadian clock which is located in the suprachiasmatic nucleus . It is most effective for sleep onset insomnia and can be used for long term treatment. To date it has no shown no abuse potential, unlike other sleep medications which may be habit forming.
If you are having difficulty with insomnia, a good place to start is to discuss your concerns with your primary care physician. Different treatments can be considered. Sleeping medications can be helpful in preventing sleeplessness in America but do not yet rival the quality of natural sleep. They treat the symptoms of insomnia but not the insomnia itself. Next time we will explore effective cognitive behavioral techniques to promote natural sleep. These techniques have the benefit of directly treating the causes of insomnia. So-no moths, just a good night's sleep- coming up!
