According to a major 2003 survey, about 20% of American older adults use some form of sleep aid--including prescription or over-the-counter drugs, alcohol, or some combination. Furthermore 15% use such aids every night.
It should be stressed that only behavioral or psychologic techniques can actually cure insomnia, whereas prolonged use of sleeping pills can only result in dependency. In addition, a 2002 study reported lower survival rates in people who took sleeping pills, although more research is needed to clarify this association.
In general, the following precautions are important in taking sleeping pills:
- Start with non-prescription medication.
- Drugs used specifically for improving sleeping are called hypnotics. If prescription hypnotics are required, start with as low a dose as possible. Discuss with the physician the benefits and risks of benzodiazepines versus non-benzodiazepines. Until recently benzodiazepines were most commonly prescribed, but newer non-benzodiazepines a may be better tolerated and have less risk of dependency. In general, hypnotics should generally be used only to prevent the vicious cycle of psychophysiologic insomnia in people with transient or short-term insomnia when non-medical treatments have failed.
- As a general rule, do not take either prescription nor non-prescription sleeping pills on consecutive days or for more than two to four days a week.
- If insomnia is still a problem after stopping the drug and continuing with good sleep hygiene, this pattern can be repeated again, but for no longer than four weeks.
- Medication should be withdrawn gradually and the patient should be aware of the possibility of rebound insomnia when stopping medication.
- Alcohol intensifies the side effects of all sleeping medication and should be avoided.
- If chronic insomnia is a companion to depression or anxiety, treating these problems first may be the best approach. Some newer antidepressants, such as nefazodone (Serzone), may be effective at treating both depression and insomnia at once.
Common Non-Prescription Drugs
Over-the-counter and prescription sleeping medications are very commonly used medications.
Brands with Antihistamines. Antihistamines cause drowsiness and many over-the-counter preparations are available that might help transient insomnia.
- Most over the counter sleep aids use antihistamines ingredients, most commonly diphenhydramine. They may simply contain diphenhydramine alone (Nytol, Sleep-Eez, Sominex) or contain combinations of diphenhydramine with pain relievers (Anacin P.M., Exedrin P.M., Tylenol P.M.).
- Doxylamine (Unison) is another antihistamine used in sleep medications.
- Certain antihistamines indicated only for allergies, such as chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), or hydroxyzine (Atarax or Vistaril) may also be used as mild sleep-inducers.
Unfortunately, most of these drugs can leave patients drowsy the next day and may not be very effective in providing restful sleep. Side effects include the following:
- Daytime sleepiness.
- Drunken movements.
- Blurred vision.
- Dry mouth and throat.
In general, they should be avoided by people with angina, heart arrhythmias, glaucoma, problems urinating, or while taking medications to prevent nausea or motion sickness. Some, such as those containing doxylamine should also be avoided by patients with chronic lung disease.
Common Pain Relievers. When sleeplessness is caused by minor pain, simply taking an acetaminophen (Tylenol) or an NSAID, such as ibuprofen (Advil, Motrin) can be very helpful without causing any daytime sleepiness. The extra P.M. antihistamine found in combination products is simply an extra, needless chemical in these situations.
Many people with insomnia choose herbal remedies for treating their insomnia. Some such as chamomile tea or lemon balm are harmless for most people. It should be strongly noted that a being labeled "natural" is neither equal to being safe or necessarily to even being natural. Herbal remedies are not regulated. Some even contain conventional medicines.
Melatonin. Melatonin is the best studied natural remedy for insomnia, although in the US it remains unregulated. Evidence on its effects remains unclear. Some studies have found that although many people fall asleep faster with melatonin, it has no effect on total sleep time or daytime feeling of sleepiness or fatigue. One difficulty in assessing study results is that there are no consistent standards on melatonin dosages or usage. Some research suggests that 0.3 mg may be the most effective dosage in many people with insomnia. Of note, however, a 2003 study reported no benefits for people with chronic insomnia from either 0.3 mg or 1.0 mg of melatonin. Higher doses (3 to 5 mg) may even keep some people awake.
Although it may not have many benefits for most people with chronic insomnia, studies suggest that it may help specific individuals, such as the following:
- Elderly people. It may help certain older people with insomnia, such as those with evidence of low melatonin levels and those dependent on prescription sleeping medications. It is not clear, however, how significant the benefits are.
- People without sight. A 2000 study reported that melatonin can help people without sight retrain their circadian cycle so that they can sleep at regular hours. The best dosages and timing, however, need to be clarified. High doses (10 mg) may be needed to start with, but can probably be reduced over time.
- Travelers and jet lag. Some studies have reported that melatonin may help prevent jet lag in some travelers. The optimal dosages or timing for preventing jet lag are still unclear, however.
- During withdrawal from prescription sleep medication. Melatonin may help people who are dependent on sleeping medications withdraw from these agents and maintain good quality sleep.
- People with delayed sleep syndrome. It might be somewhat helpful for people with who fall asleep very late at night or in early morning hours but then they sleep normally.
- Children. Melatonin may be effective and safe for children with chronic insomnia. In one small study, or example, melatonin was specifically helpful for children with Asperger's syndrome, who are at risk for sleep disturbances. More research is warranted, however. At this time, no one should give their child melatonin, which is a potent hormone and not regulated in the US, without a doctor's recommendation.
Melatonin is a powerful hormone that can have major effects on all parts of the body. Doses of melatonin over 0.3 can disrupt the circadian system in the brain and long-term consequences are unknown. High doses have been associated with the following adverse events:
- Mental impairment.
- Severe headaches.
Interactions with other drugs are not completely known. It should be stressed that melatonin is currently classified as a dietary supplement and not as a drug, so its quality and effectiveness is uncontrolled in the US. (The United States is the only developed nation that does not regulate this agent.) The bottom line is that at this time, people who take melatonin are experimenting on themselves.
Valerian root. Valerian is an herb that has sedative qualities and has been helpful in people with insomnia. One study reported that it was also useful for helping patients withdraw from benzodiazepines--the standard prescription sleeping pills. In another study, 82.8% patients rated the effects of valerian (Sedonium) on sleep as very good. In the same study, valerian was as effective as oxazepam, a standard prescription sleeping medication. This herb is listed on the FDA's list of generally safe products. Side effects include vivid dreams. It should be noted that high doses of valerian can cause blurred vision, excitability, and changes in heart rhythm. Of note, however, its effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. As with all herbal remedies, the quality of individual brands is unregulated.
Chamomile. Many people drink chamomile tea for its sedative properties. Although it appears to be safe, it may cause allergic reactions in people who have plant or pollen allergies. Also, as with any agent that affects the nervous system, it should not be used with if a person is taking sleeping agents or drugs that are used for neurologic or psychiatric problems or otherwise affect the central nervous system.
Warnings on Alternative and So-Called Natural Remedies
Alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Even if studies report positive benefits from herbal remedies, the compounds used in such studies are, in most cases, not what are being marketed to the public. There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication.
The following warnings are of particular importance for people with insomnia:
Chinese Herbal Remedies. Studies suggest that up to 30% of herbal patent remedies imported from China having been laced with potent pharmaceuticals such as phenacetin and steroids. And one study reported a significant percentage of such remedies containing toxic metals. For example, the herbal remedy Sleeping Buddha was recalled in 1998 because it actually contains a benzodiazepine, the major ingredient in many prescription sleeping pills, and also appeared to increase the risk for birth defects in pregnant women. Reports of a few cases of acute hepatitis have occurred from Jin Bu Huan, a Chinese herbal remedy sold as treatment for pain and insomnia.
Kava. Kava has been used to relieve anxiety and improve sleep. It is not generally considered safe, however, after reports of liver failure and death from this medication, with highest risk in those with liver disease. Other side effects include itchy, scaly skin, muscle weakness, and problems with coordination. It also interacts dangerously with certain medications, including alprazolam, an anti-anxiety drug. And it increases the potency of certain other drugs, including other sleep medications, alcohol, and antidepressants.
Tryptophan and 5-L-5-hydroxytryptophan (HTP). Tryptophan is an amino acid used in the formation of the neurotransmitter serotonin, which is known to promote well-being and has been associated with healthy sleep. L-tryptophan was marked for insomnia and other disorders but was withdrawn from the market after contaminated batches caused a rare and even fatal disorder called eosinophilia myalgia syndrome. 5-htp, a byproduct of tryptophan, is still available as a supplement. There have been reports that some brands contain a substance called Peak X, which some evidence suggests may be harmful. To date, no serious adverse effects have been reported and reliable brands are available. Evidence that 5-HTP alleviates insomnia is scant.
The following website is building a database of natural remedy brands that it tests and rates. Not all are yet available and the information requires a paid subscription (www.consumerlab.com).
The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (800-332-1088).
Benzodiazepines, also referred to as benzodiazepine receptor agonists (BzRAs), were once the most commonly prescribed sedative hypnotics. Originally developed in the 1960s to treat anxiety, these drugs nonselectively target receptor sites in the brain that modulate the effects of the neurotransmitter gamma-aminobutyric acid (GABA).
Brands. Commonly prescribed benzodiazepines include the following:
- Long acting benzodiazepines include flurazepam (Dalmane) and clonazepam (Klonopin), quazepam (Doral).
- Medium- to short-acting benzodiazepines include triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), oxazepam (Serax), prazepam (Centrax), estazolam (ProSom), and flunitrazepam (Rohypnol). Short-acting benzodiazepines are particularly useful for air travelers who want to reduce the effects of jet lag.
Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long- or shorting acting. They include the following:
- The drugs may increase depression, a common co-condition in any case in many people with insomnia.
- Respiratory depression may occur with overuse or with people with pre-existing respiratory illness.
- Long-acting agents have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
- Memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states have been reported after taking Halcion and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
- Incontinence. (In one 2002 study, 33% of patients experienced incontinence at least twice a week. The risk is highest in the elderly and with older, long-acting agents.)
- Because these drugs cross the placenta and enter breast milk, pregnant women or nursing mothers should not use them. An association was reported between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns.
- In rare cases, overdoses have been fatal.
Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol, and some medications, like the ulcer medication cimetidine, can slow the metabolism of the benzodiazepine.
Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last one to three weeks after stopping the drug and may include the following:
- Gastrointestinal distress.
- Disturbed heart rhythm.
- In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.
Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes one to two nights of sleep disturbance, daytime sleepiness, and anxiety. In some cases patients may experience the return of original severe insomnia. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.
Newer short-acting non-benzodiazepines can induce sleep with fewer side effects than the benzodiazepines. Both benzodiazepine and non-benzodiazepine sedative hypnotics act on GABA-A receptor sites in the brain, but non-benzodiazepines are more specific in the subunits they target. Developed in the late 1980s, these drugs are increasingly prescribed and are becoming the hypnotics of choice for many physicians.
Brands and Benefits. Non-benzodiazepine hypnotics currently approved in the United States are zolpidem (Ambien) and zaleplon (Sonata). A third drug, zopiclone (Imovane), has been available for many years in Europe and other markets. The brands have some differences, such as the following:
- Zolpidem (Ambien) has become one of the most commonly prescribed drugs for insomnia. It is longer acting than zaleplon and patients should not take it unless they plan on getting at least 7-8 hours of sleep. The recommended dose is 10 mg/day for adults and 5-10 mg/day for the elderly. A 2002 study suggested that the drug might be used on an as-needed basis, with up to five tablets taken a week. After three weeks, two-thirds of the patients taking zolpidem in this way were able to reduce their tablet intake by more than 25% without losing improvements in sleep.
- Zaleplon (Sonata) is the shortest-acting hypnotic available. Because it is more rapidly eliminated from the body it may be most effective for people who have difficulty falling asleep, but may not be as effective for maintaining sleep throughout the night. The drug takes effect within 30 minutes and may be taken at bedtime or later in the night as long as the patient can sleep for at least 4 hours. The recommended dose is 5-10 mg/day and typical recommended duration of use is 7-10 days.
- Zopiclone (Imovane) is the longest acting agent of this group. It still carries a low risk for daytime drowsiness, however. Zopiclone was the first non-bezodiazepine hypnotic to be approved and has been used for many years in Europe, but not the United States. A derivative of zopiclone, called eszopiclone, is currently under consideration for approval in the United States.
These agents can be particularly helpful for preventing jet lag (but zolpidem should not be used on flights less than 7-8 hours). They also may be beneficial for people who also have accompanying mood disorders, such as depression or post-traumatic stress disorder. Because they are short-acting, zaleplon and zolpidem may pose fewer risks for falls and memory loss in elderly patients. In general, these drugs are recommended for short-term use (7-10 days) and treatment should not exceed 4 weeks. No studies have yet confirmed safety for longer-term use.
Side Effects. All of these agents have fewer morning side effects than the benzodiazepines, including morning sedation and memory loss (although they can occur to some degree). Ambien's record of adverse effects is similar to that of triazolam (Halcion), the short-acting benzodiazepine. Sonata appears to have less severe side effects. In general, the side effects are mild but can include the following for one or all of these agents:
- Agitation or antagonistic mood in the morning.
- Amnesia (in high doses).
- Visual distortion
- Rare reports of kidney injury.
- Rare fatal overdoses have been reported.
Interactions. As with any hypnotics, alcohol increases the sedative affects of these drugs. These hypnotics also interact with other agents, including rifampin, ketoconazole, erythromycin, and cimetidine. They may also interfere or be interfered by other agents. Patients should report all medications to their physicians.
Dependency, Withdrawal Symptoms, and Rebound Insomnia. The risk for rebound insomnia, dependence, and tolerance is lower with these agents than with benzodiazepine, particularly with Sonata. In one study, people who took this hypnotic every night for one year had no evidence of dependency or withdrawal symptoms, but more large studies are needed to confirm long-term safety. These agents are still subject to abuse. In any case, no hypnotic should be taken for more than 7-10 days or at higher than the recommended dose without a doctor's approval.
Antidepressants are sometimes used to treat insomnia that may be caused by depression (secondary insomnia). In addition, some antidepressants with sedating properties are prescribed for the treatment of primary insomnia. For example, trazodone has been frequently prescribed in low doses as a hypnotic to help induce sleep. However, there is a paucity of studies that address its safety and efficacy as a drug for treating insomnia in non-depressed patients. Several studies have warned against trazodone's use in elderly patients, due to its risk for side effects (daytime sleepiness, dizziness, priapism) and drug interactions. In fact, however, all hypnotics can have serious side effects in the elderly, and all must be used with caution.
Drugs Under Investigation for Insomnia
Eszopiclone. Eszopiclone (Estorra) is a new non-benzodiazepine hypnotic that appears to improve both sleep maintenance and daytime alertness and functioning. It is also being studied for long-term treatment of insomnia. In one study, patients took the medication for a year without suffering loss of effect. At the time of this report, a new drug application for Estorra had been submitted to the FDA. If approved, Estorra may be available to patients by early 2005.
Indiplon. Indiplon is another new non-benzodiazepine agent that may be submitted for approval within the next year. Early studies suggest it is effective and does not cause a rebound effect during withdrawal.
Gaboxadol. Gaboxado is not as far along in the drug development process as eszopiclone or indiplon, but late-stage trials have begun. If the drug is successfully approved, it will probably become available in 2007.
Older Agents Rarely Used
Chloral Hydrate. Chloral hydrate has been in use since 1832. It has significant adverse effects, however, and most experts believe it no longer has a role in the treatment of insomnia. In any case it does not appear to be effective in the elderly. Chloral hydrate poses a risk for addiction and it can be fatal in overdose. It also has carcinogenic properties and can harm genetic material. Potential side effects also include irritation of the skin, mucous membranes, and stomach. People with stomach, heart, kidney, or liver disorders should not take this drug at all. If a child is given it (usually for minor surgery), then that child should never be given chloral hydrate again in his or her lifetime.
Barbiturates. Barbiturates (Seconal, Nembutal) were the standard sleeping medication before the introduction of benzodiazepines. Overdose is dangerous and frequent; addiction and abuse are common. At present these drugs should rarely or never be prescribed for insomnia.
Treating Children with Insomnia
There are few studies on the appropriate treatment for children with severe insomnia. The physician should first rule out any treatable causes or situations. Behavioral treatments are the first-line therapies for children. Some medications are thought to be safe by some experts and have been used in certain cases, but none have been approved by the FDA for children. Such medications include the long-acting benzodiazepine flurazepam (Dalmane) and certain antihistamines, such as trimeprazine (Temaril). Short-acting benzodiazepines may have some use for brief treatment of children with insomnia related to mood disorders or medication. Long-term use of any sleeping medication is rarely, if ever, warranted.
Treating Insomnia in the Elderly
Long-acting benzodiazepine hypnotics are often used in nursing homes, where the institutional setting, nighttime light and noise, and the underlying medical problems of older patients worsen sleeplessness. It is in the staffs interest to have sleeping times as regimented as possible, so as to promote good sleep.
The chronic use of the older sleeping pills in the elderly, however, can produce side effects, such as impaired memory and alertness, urinary incontinence, daytime sleepiness, and imbalance, that can make care even more difficult in the long run. The newer short acting benzodiazepines and the hypnotic non-benzodiazepines may not pose such risks, but studies are needed to confirm this. Zolpidem (Ambien) may be especially safe and effective in this group. In the meantime, behavioral therapy is proving to be useful even in older adults and, as in younger people, should be tried first. Light therapy may be particularly beneficial for nursing home residents.
Treating Insomnia During Menopause
Hormone Replacement Therapy. Hormone replacement therapy may be useful for women with insomnia associated with hot flashes and sweating. (There are both risks and benefits to this therapy, which a woman should discuss with her physician.)
Clonidine (Catapres), a drug known as an alpha-2 agonist, is used for Tourette's syndrome and hypertension. Some evidence suggests it may be useful for hormone-related symptoms of menopause.
Behavioral Techniques. Nonmedical treatments are recommended for women whose insomnia is related to stress and emotional distress. If insomnia continues in spite of strong efforts, hypnotics or antidepressants may be useful.
Treating Insomnia in Shift Workers
Shift workers should sleep in a completely darkened room and wear dark glasses during the day.
Light Therapy. Shift workers may benefit from sitting in front of a light box before starting a night shift. One study indicated that even moderate light was effective with this method.
Treating People with Both Depression and Insomnia
When insomnia appears to be caused by depression, the use of antidepressants should be considered as a first option. Often, the insomnia will clear up along with symptoms of depression. Many doctors appear to be prescribing antidepressants even to insomnia patients who may not be clinically depressed, a strategy for which there is little evidence.
Of notable benefit for depressed patients with insomnia appear to be newer antidepressants, such as mirtazapine (Remeron), that affect serotonin and other brain chemicals. It should be noted that many common antidepressants, such as fluoxetine (Prozac), paroxetine (Paxil), and other so-called SSRIs, can cause insomnia. Some research suggests that the newer hypnotics, notably zolpidem (Ambien), may be useful for insomnia experienced by people taking these agents.
All antidepressants have side effects and interactions with other medications that should be discussed with the physician.