American Insomnia Association

Insomnia is an occasional problem for at least a third of the population. For many, insomnia is not an isolated situation, but a chronic condition. Accurate diagnostic assessment is important, with a particular focus on the link between chronic insomnia and mood disturbances. With chronic insomnia, one can experience difficulties with concentration or performance in the workplace. Clearly, given that insomnia occurs commonly, the economic and social impact can be great. The treatment of insomnia should always include education and assessment of sleep behaviors. It may also include treatment with medication (pharmacotherapy). The use of medications in the treatment of insomnia should be flexible. It is important to assess the individual needs of the patient before making specific recommendations. Each patient needs to be evaluated by his/her physician, and individual treatment needs will vary.

It is likely that humans have attempted to control states of sleep and wakefulness since the beginning of time. There are early reports of the use of herbal potions, alcohol, and laudanum to induce sleep. However, the first reports regarding a medication used to promote sleep were in the mid 19th century and related to the drug known as bromide. Bromide was initially developed for the treatment of epilepsy, but was soon found to be effective as a tranquilizer and sedative. This medication was prone to producing toxicity and serous adverse effects and was removed from the marketplace several years ago.

Following the introduction of bromide, other sedative-hypnotics were developed. These included drugs such as chloral hydrate, paraldehyde, urethane, and sulfonal. However, in the early 1900s a new class of drug was developed that represented an important advancement in sleep therapy. The drugs in this class are known as barbiturates (such as amobarbital, pentobarbital, secobarbital, and phenobarbital). They were known to be quite effective in promoting sleep and were used quite commonly until the 1960s when safety concerns and newer medications resulted in a decline in prescriptions. Barbiturates were found to have a wide variety of effects on the body, were associated with multiple adverse effects, and were extremely dangerous, or lethal, when taken in overdose.

In the 1960s, the benzodiazepines were introduced for the treatment of insomnia. These medications were shown to be effective and safe medications. Most notably, they were much less likely to produce adverse effects, and much less likely to be fatal when taken in overdose than the barbiturates. Benzodiazepines are still in use today for the treatment of insomnia, anxiety, and seizures. They are less often prescribed now than in the past, however, because of concerns regarding next day "hangover," or residual effects.

In the 1990s a newer class of medications, known as "non-benzodiazepine, benzodiazepine receptor agonists" were introduced for the treatment of insomnia. The drugs in this class are as effective as the benzodiazepines in promoting sleep. However, they are believed to be associated with a very low risk of abuse or dependence and fewer adverse effects than the benzodiazepines.

Newer prescription medications for insomnia are currently in development. The goal of new medications is usually to match or exceed the effectiveness of the existing drugs on the market, have fewer adverse effects and to have better safety profiles.

These are medications approved by the FDA for use in the treatment of insomnia. There are now five benzodiazepine compounds (Valium-like drugs) and three non-benzodiazepine compounds approved for use. It has been estimated that 2.5% of the population will take a hypnotic for insomnia within a given year. In addition to these prescription medications there are non-prescription hypnotics available over the counter, along with other medications (including a variety of antidepressants) that may be given by physicians to their patients to aid in either the onset or maintenance of sleep.

Use of medications must take into account not only nighttime problems but the daytime consequences of poor sleep. An accurate diagnosis must be the first goal. Is the insomnia secondary to a medical condition or depression? Is it related to transient stressors either at home or at the workplace? Does the patient have pets that are in the bedroom and may be contributing to disrupted sleep? These are just a few of the questions that your physician will need to address before deciding on whether or not medications are indicated for treatment.

For a medication to be approved by the Food and Drug Administration (FDA) as a hypnotic it must first prove to be effective when tested in a controlled setting and against a placebo. The hypnotics that will be described here have been tested and have met FDA requirements to be marketed as an aid for sleep. These medications have generally replaced older hypnotics, such as chloral hydrate, which are not as safe (and can cause serious respiratory depression, among other concerns) and are no longer used.

The benzodiazepine (Valium-like) medications are thought to work through their actions at a specific neurotransmitter receptor site (part of the GABA receptor complex). These hypnotic medications are all rapidly absorbed after being administered. They differ in their speed of action as well as the length of time that they are active. For example, one of the medications, Halcion (triazolam) has a very rapid onset of action, and is also out of the system quickly. Other agents, such as Dalmane (flurazepam), have a much longer duration of action and have metabolites that may cause next-day drowsiness for some patients. The physician must decide which of the available medications in this class would be the right choice for an individual based on complaints of onset, maintenance or early morning awakening insomnia. This group of medications does have the potential of being habit forming and is best avoided in patients known to have a history of substance abuse or dependence. Below is a table of the benzodiazepine agents and their dosage that are currently approved for use as hypnotics.

Medications	generic name	half life	dosage
Dalmane	flurzepam	48-120 hours	15-30mg
Doral	quazepam	48-120 hours	7.5-15mg
Halcion	triazolam	2-6 hours	.125-.25mg
ProSom	estazolam	8-24 hours	1-2mg
Restoril	temazepam	8-20 hours	15-30mg

There are now three medications in this class that are approved by the FDA in the treatment of insomnia. These agents are thought to work through their action on one of the subtypes of the GABA-benzodiazepine receptors. All three of these medications have been found to be safe and effective in the treatment of insomnia. They differ primarily in their duration of action. Once again, it is important to determine whether difficulty with initiation of sleep, sleep maintenance, or perhaps both, is the primary complaint. As you would expect, all of these medications have been shown through research to improve sleep quality. They are thought to be safe, and the newest of the medications (eszopiclone) has proven to be effective for nightly use over a duration of six months. Below is a table of the half-life and dosages for these medications.

Medications	generic name	half life	dosage
Ambien	zolpidem tartrate	1.5-2.4 hours	5-10mg
Sonata	zaleplon	1 hour	5-10mg
Lunesta	eszopiclone	5-7 hours	1-3mg

Many of the common over-the-counter medications used to induce sleep contain antihistamine agents. These agents are sedating, but they also have significant side effects. The main concern with these drugs involves next-day effects. Studies that have evaluated psychomotor skills, visual processing and even driving performance have confirmed that many of the commonly used antihistamine agents can cause impairment. In addition, adverse effects can include dry mouth, dry eyes, confusion and urinary retention.

Sometimes physicians will use sedating antidepressants to help patients with a variety of problems, including, but not restricted to depression. Medications in this class include amitriptyline, nortriptyline, doxepine and trazodone. For some patients, sleepiness in the daytime may be a problem, but these effects tend to diminish over time. In some patients the medications may actually worsen problems such as periodic limb movement disorder. In patients with fibromyalgia, however, sedating antidepressants may decrease pain. In patients whose insomnia is secondary to depression or anxiety, there will be improvement of sleep as the underlying mood or anxiety disorders improve.

"Natural," Herbal, and Other Home Remedies have been used for years. One of the most recent "natural" remedies for insomnia has been melatonin, which can be obtained at most health food stores. Melatonin is a hormone that is known to be involved in the regulation of sleep and wakefulness. It has been shown that the ingestion of melatonin prior to bedtime will help individuals fall asleep. However, scientific data have failed to confirm that melatonin is useful in maintaining sleep.

Herbal products such as valerian, chamomile, kava kava, and others have been promoted as natural remedies for insomnia. However, the effectiveness and safety of these products has not been documented.

It is important to note that products sold in health food stores have not been exposed to the rigorous testing that is required of all prescription products. Therefore, many of the claims that are made regarding these substances have not been adequately tested in a laboratory environment. The content of these products is also not regulated with the same scrutiny as prescription products, so consumers may not be certain of what they are getting. Finally, the safety profiles of these products are often not known. Several years ago many people used the substance tryptophan, an amino acid, to promote sleep. Dozens of users were then affected by a serious disorder called eosinophilia myalgia syndrome (EMS) due to a contaminant that entered the product during its manufacturing. Tryptophan has since been removed from the market in the United States.

Treatment of insomnia can be complicated; it usually involves not only pharmacotherapy, but also non-pharmacologic treatment. This non-pharmacologic treatment usually includes a reduction or elimination of caffeine and alcohol use, improved eating habits, establishing an exercise routine and keeping a relaxing bedtime routine. Your physician may ask you to log your sleep for several weeks to get a sense of your routine and to see where you are having the most difficulty. An approach that takes into account not only medications but sleep habits as well is much more likely to be effective.

1. Nowell PD, Buysse DJ, Reyjnolds CF, et al. Clinical factors contributing to the differential diagnosis of primary insomnia and insomnia related to mental disorders Am J Psychiatry 1997;154(10):1412-6
2. Krystal, AD, Walsh, J.K., Laska E et. Al. Sustained Efficacy of Eszopliclone Over 6 Months of Nightly Treatment. Sleep, 2003;26 (7):793-799.
3. Butler MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. J. Clin Psychiatry 1992; 53 Suppl: 34-9.

Modern day sleep medications are not dangerous when used as prescribed. The addictive potential of the newest classes of medication is believed to be low.

When can sleep medications be used?

Sleep medications can be used on a periodic basis, when needed to combat insomnia. Many people experience insomnia only a few times per year or per month. It is appropriate to use the medication in this way, provided that your doctor has recommended it.

Sleep medications also may be used on a nightly basis. Current prescription guidelines indicate that sleep medications should be used on a continuous basis for a limited period of time (a few weeks). However, data show that some people use the medication for longer periods. These people may have chronic problems with insomnia that require chronic treatments.

Most sleep medications need to be taken just before bedtime or at bedtime. This is due to the persistence of their effects over the course of the night. Some sleep medications may be able to be taken after bedtime, in response to symptoms or awakenings. Those who use sleep medications should speak with their doctors regarding appropriate use.

No single therapy is better than any other. Since insomnia often arises from a variety of causes, and different people have different desires and attitudes regarding medication, it is hard to say that "one size fits all" with regard to insomnia treatment. It is most important that patients talk to their doctors about their problems, what they hope for with treatment, and assess progress along the way.

Some people will use a sleeping pill for one night. Others may need long-term use of the medication on a nightly basis. If you use sleep medications over the long-term, it is important to maintain regular contact with your physician to determine the need for continued use and explore all of the options open to you. For example, in some cases a persistent problem with insomnia is a sign that other, underlying sleep problems exist. These need to be diagnosed and treated in order to find real relief.

Yes. Newer sleep medications can be discontinued in a matter of a day or two, usually without withdrawal effects. Benzodiazepines may require a longer period of "tapering" before they actually can be discontinued. However, if managed properly, the discontinuation can be tolerated comfortably.