About 20% or more of older American adults use some form of sleep aid, including prescription or over-the-counter drugs or alcohol. Many use such aids every night. Over-the-counter (nonprescription) medications make use of the drowsiness caused by some common medications. Prescription drugs used specifically for improving sleeping are called sedative hypnotics. These drugs include benzodiazepines and non-benzodiazepines.
Sedative hypnotics carry risks for withdrawal, dependency, and rebound insomnia. The chance of risk for these problems varies among different drugs.
Common Non-Prescription Sleep Medications
Brands with Antihistamines. Many over-the-counter sleeping medications use antihistamines, which cause drowsiness. Diphenhydramine is the most common antihistamine used non-prescription sleep aids.
Some drugs contain diphenhydramine alone (such as Nytol, Sleep-Eez, and Sominex), while others contain combinations of diphenhydramine with pain relievers (such as Anacin P.M., Excedrin P.M., and 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 leave patients feeling drowsy the next day and may not be very effective in providing restful sleep. Side effects include:
- Daytime sleepiness
- Cognitive impairment
- Drunken movements
- Blurred vision
- Dry mouth and throat
In general, people with angina, heart arrhythmias, glaucoma, or problems urinating should avoid these drugs. They should not be used at the same time as medications that prevent nausea or motion sickness. Patients with chronic lung disease should also avoid some non-prescription sleeping aids, such as those containing doxylamine.
Common Pain Relievers. When sleeplessness is caused by minor pain, simply taking acetaminophen (Tylenol) or a non-steroidal anti-inflammatory drug (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.
Newer short-acting non-benzodiazepines can induce sleep with fewer side effects than 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 now the preferred sedative hypnotic drugs for the treatment of insomnia. In general, these drugs are recommended for short-term use (7 - 10 days), and treatment should not exceed 4 weeks.
Brands. Non-benzodiazepine hypnotics currently approved in the United States are:
- Zolpidem (Ambien, Ambien CR, generic) is one of the most commonly prescribed drugs for insomnia. It lasts longer than zaleplon. Patients should not take it unless they plan on getting at least 7 - 8 hours of sleep.
- Zaleplon (Sonata) is the shortest-acting hypnotic available. Because it is rapidly eliminated from the body it may be best for people who have difficulty falling asleep, not those who wake up often throughout the night. The drug takes effect within 30 minutes and may be taken at bedtime or later as long as the patient can sleep for at least 4 hours.
- Eszopiclone (Lunesta) may help improve both sleep maintenance and daytime alertness. Eszopiclone is related to zopiclone (Imovane), which has been used for many years in Europe. Unlike other sleep medications, eszopiclone was the first sleep medication approved to be taken on a long-term basis.
- Ramelteon (Rozerem) is the newest type of sedative hypnotic but it is not technically a non-benzodiazepine hypnotic. Unlike other prescription sleep drugs, which target GABA receptors, ramelteon works by targeting melatonin receptors. Ramelteon is not habit forming and is the first sleep drug not designated as a controlled substance.
Side Effects. All of these drugs have fewer morning side effects than the benzodiazepines, including morning sedation and memory loss (although they can occur to some degree). When patients first start taking any of these drugs, they should use caution during morning activities until they are sure how the drug affects them.
General side effects may include:
- Unpleasant taste
All non-benzodiazepine drugs carry labels warning that that these drugs can cause sleep-related behavior, including driving, making phone calls, and preparing and eating food while asleep. (Most cases of sleepwalking and sleep driving likely occur when patients use zolpidem along with alcohol or other drugs or take more than the recommended dose.) In addition, severe allergic reactions (anaphylaxis) and facial swelling (angioedema) can occur even the first time one of these drugs is taken.
Anyone who receives a prescription for these medicines will get a patient medication guide explaining the risks of the drugs and the precautions to take. Talk to your doctor if you have any questions concerning these drugs or their potential side effects.
Patients should carefully read the information labels for all drugs and follow the directions. Some sleeping pills take 30 - 60 minutes to take effect, while others (such as zolpidem) act quickly. For zolpidem, patients should:
- Take zolpidem immediately before going to sleep
- Take zolpidem only when able to get a full night’s sleep (7 - 8 hours)
- Not drink alcohol the same evening
- Not take more than the prescribed dose
- Use caution in the morning when getting out of bed, driving, or operating heavy machinery
Interactions. As with any hypnotics, alcohol increases the sedative effects of these drugs. These hypnotics also interact with other drugs, including rifampin, ketoconazole, erythromycin, and cimetidine. They may also interfere with or be interfered by other drugs. Patients should report all medications to their doctors.
Dependency, Withdrawal Symptoms, and Rebound Insomnia. The risk for rebound insomnia, dependence, and tolerance is lower with non-benzodiazepine hypnotics than with benzodiazepine drugs. These drugs 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.
Benzodiazepines used to be 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).
The risk of tolerance and dependence is higher with this group of drugs than with non-benzodiazepine hypnotics.
Brands. Commonly prescribed benzodiazepines:
- Long-acting benzodiazepines include flurazepam (Dalmane), clonazepam (Klonopin), and 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 may be 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. They should not take long-acting forms.
Side effects may differ depending on whether the benzodiazepine is long or shorting acting. They include:
- Severe allergic reactions, including facial swelling, can occur even with the first use of a benzodiazepine drug.
- Respiratory problems may occur with overuse or in people with pre-existing respiratory illness
- The drugs may increase depression, a common co-condition in many people with insomnia.
- Respiratory depression may occur with overuse or with people with pre-existing respiratory illness.
- Long-acting drugs have a very high rate of residual daytime drowsiness compared to other types of sleeping pills. 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, sleepwalking, sleep driving, eating while asleep, and other odd mood states may occur. These effects are enhanced by alcohol.
- Urinary incontinence may occur, particularly in elderly patients and when taking long-acting formulations.
- Because these drugs cross the placenta and enter breast milk, pregnant women or nursing mothers should not use them. Benzodiazepine use in the first trimester of pregnancy may be associated with the development of cleft lip in newborns.
- In rare cases, overdoses can be fatal.
Interactions. Benzodiazepines are potentially dangerous when combined with alcohol. 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 1 - 3 weeks after stopping the drug and may include:
- 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 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. In some cases, patients may experience the return of the original severe insomnia. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.
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, generally in lower doses than used to treat depression.
For example, trazodone has been frequently prescribed in low doses as a hypnotic to help induce sleep. A new, very low dose formulation of doxepin (Silenor) has recently been approved for treatment of insomnia. Other antidepressants used for insomnia include trimipramine, amitriptyline, and mirtazipine. Care should be taken in the use of trazodone and other sedating antidepressants in elderly patients, due to the risk for side effects (daytime sleepiness, dizziness, and priapism) and drug interactions.
Herbs and Supplements
More than 1.5 million Americans use complementary and alternative therapies to treat insomnia. Many people choose herbal and dietary supplement remedies. (Valerian and melatonin are among the most popular alternative remedies for insomnia.) Some, such as chamomile tea or lemon balm, are generally harmless for most people. Others have more serious side effects and interactions.
The American Academy of Sleep Medicine (AASM) advises that there is only limited scientific evidence to show that herbal and dietary supplements are effective sleep aids. The AASM recommends that these products should be taken only if approved by a doctor. Be sure to talk to your doctor if you are considering taking any herbal or dietary supplement. Some of these products can interact with prescription medications.
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.
Melatonin. Melatonin is the most studied dietary supplement for insomnia. It appears to reduce the time to fall asleep (sleep onset) and the time spent asleep (sleep duration). However, there are no consistent standards on melatonin doses. Some research suggests that 0.3 mg may be the most effective dosage in many people with insomnia. However, higher doses may keep some people awake and may also cause mental impairment, severe headaches, and nightmares. Although melatonin may not have many benefits for most people with chronic insomnia, studies suggest that it may help travelers with jet lag and people with delayed sleep syndrome.
Valerian root. Valerian is an herb that has sedative qualities and is commonly used by people with insomnia. Some studies have indicated that it may help improve the quality of sleep, but there have been few rigorous and well-conducted trials to prove it is effective.
Kava. Kava has been used to relieve anxiety and improve sleep. It is not safe. There have been reports of liver failure and death from this herb, with highest risk in those with liver disease. Kava can interact dangerously with certain medications, including alprazolam, an anti-anxiety drug. Kava also increases the strength 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 associated with healthy sleep. L-tryptophan used to be marketed for insomnia and other disorders but was withdrawn after contaminated batches caused a rare but serious and even fatal disorder called eosinophilia myalgia syndrome. 5-HTP, a byproduct of tryptophan, is still available as a supplement. There is little evidence that 5-HTP relieves insomnia.