Many Americans use some form of herbal, over the counter, or prescription sleep aid pill. 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.
Herbs and Supplements
More than 1.5 million Americans use complementary and alternative therapies to treat insomnia. Valerian and melatonin are among the most popular herbal and supplement remedies for insomnia. Chamomile tea and lemon balm are also popular. These substances are generally harmless for most people. However, other herbs and supplements 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. People should always check with their doctors before using any herbal remedies or dietary supplements.
Melatonin is the most studied dietary supplement for insomnia. It appears to reduce the time to fall asleep (sleep onset) and may be effective in treating delayed sleep phase syndrome. However current evidence does not support the use of melatonin for primary or secondary insomnia. There are no consistent standards on melatonin doses and its safety has only been assessed for short-term use. General recommendations are to take 0.3 mg to 1 mg about 90 minutes before going to sleep. Taking higher doses may disrupt sleep and may cause daytime sleepiness, headaches, dizziness, nausea, and stomach cramps.
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 has been used to relieve anxiety and improve sleep. It is dangerous and associated with reports of liver failure and death, 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. Do not use this herb.
Tryptophan and 5-hydroxy-L-tryptophan (5-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. A byproduct of tryptophan, 5-HTP, is still available as a supplement. There is little evidence that 5-HTP relieves insomnia.
Certain Nonprescription Antihistamines
Many over-the-counter sleeping medications use antihistamines, which cause drowsiness. Diphenhydramine (Benadryl, generic) is the most common antihistamine used in non-prescription sleep aids.
Some drugs marketed as sleep aids contain diphenhydramine alone, while others contain combinations of diphenhydramine with pain relievers (such as Tylenol PM and its generic forms). Doxylamine (Unison, generic) is another antihistamine used in sleep medications. Certain antihistamines indicated only for allergies, such as chlorpheniramine (Chlor-Trimeton, generic) or hydroxyzine (Atarax, Vistaril, generic) may also be used as mild sleep-inducers.
Unfortunately, most of these drugs leave people 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. People with chronic lung disease should also avoid some nonprescription sleeping aids, such as those containing doxylamine.
Nonprescription Pain Relievers
When sleeplessness is caused by minor pain, simply taking acetaminophen (Tylenol, generic) or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Advil, Motrin, generic), 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.
Sedative hypnotics include benzodiazepines and non-benzodiazepines, which enhance the effects of the brain chemical (neurotransmitter) GABA. When GABA binds to GABA receptors, brain activity slows down, inducing calm and relaxation. There are also new types of sedative hypnotics that work in a different way by targeting receptors for melatonin or orexin.
Sedative hypnotics carry risks for dependence, tolerance, and rebound insomnia:
- Dependence means relying on a drug for falling asleep and having difficulty falling asleep or achieving restful sleep without it.
- Tolerance is being unable to fall asleep using the original dose and needing to take progressively higher doses of medication.
- Rebound insomnia can occur after stopping the drug. It typically causes 1 to 2 nights of sleep disturbance, daytime sleepiness, and anxiety. In some cases, people may experience a temporary worsening of long-term insomnia.
Non-benzodiazepines (also called "Z" drugs) are the preferred sedative hypnotic drugs for the treatment of insomnia. In general, non-benzodiazepine hypnotics are recommended for short-term use (7 to 10 days), and treatment should not exceed 4 weeks.
Non-benzodiazepine hypnotics currently approved in the United States are:
- Zolpidem (Ambien, Ambien CR, generic) is the most commonly prescribed drugs for insomnia. Because it is long-lasting, people should not take it unless they plan on getting at least 7 to 8 hours of sleep. A lower-dose, sublingual (under-the-tongue) formulation of zolpidem (Intermezzo) is approved for people who wake up abruptly in the middle of the night and have trouble falling back asleep. People take it as needed when they awaken in the night but must be able to get at least 4 hours of sleep after taking.
- Zaleplon (Sonata, generic) 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, generic) 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.
For all sleeping pills, the lowest dose that achieves symptom relief should be the chosen dose.
Recommended dosage for zolpidem products:
- All zolpidem products now have lower recommended bedtime dosages.
- Women have lower recommended dosages than men (women metabolize zolpidem more slowly than men and are more susceptible to next-day mental impairment).
- Use of higher doses increases the risk for next-day impairment of driving. In addition, the FDA warns people to refrain from next-day driving or activities involving mental alertness if they take the extended-release form of zolpidem (Ambien CR, generic).
Lower dose recommendations are also in place for eszopiclone, which can cause impairment in driving and cognitive skills for up to 11 hours after an evening dose. The FDA is currently reviewing all sleep medications to evaluate how they affect next-day mental alertness.
Non-benzodiazepines tend to have fewer side effects than benzodiazepines because they target the GABA receptor in a more specific way. However, these drugs can still cause residual morning sedation even if you are feeling fully awake. When people 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:
- Diarrhea or constipation
All non-benzodiazepine drugs carry labels warning that these drugs can cause strange 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 people use the drug along with alcohol or other drugs or take more than the recommended dose.
Anyone who receives a prescription for these medicines will get a patient medication guide explaining the risks for the drugs and the precautions to take. Talk to your doctor if you have any questions concerning these drugs or their potential side effects.
Carefully read the information labels for all drugs and follow the directions. Some sleeping pills take 30 to 60 minutes to take effect, while others (such as zolpidem) act quickly. For zolpidem, people should:
- Take zolpidem immediately before going to sleep
- Take zolpidem only when able to get a full night's sleep (7 to 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
As with any hypnotic, alcohol increases the sedative effects of these drugs. These hypnotics also interact with other drugs. Inform your doctor of all your medications.
Rebound Insomnia, Dependence, and Tolerance
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 to 10 days in a row or at higher than the recommended dose without a doctor's approval.
Benzodiazepines used to be the most commonly prescribed sedative hypnotics. These drugs were originally developed in the 1960s to treat anxiety.
Commonly prescribed benzodiazepines are:
- Long-acting benzodiazepines include flurazepam (Dalmane, generic), clonazepam (Klonopin, generic), and quazepam (Doral).
- Medium- to short-acting benzodiazepines include triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), oxazepam (Serax), and estazolam (ProSom), which are all available as generics. Short-acting benzodiazepines may be useful for air travelers who want to reduce the effects of jet lag.
Older 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 short-acting. They include:
- Respiratory problems (especially reducing how often or how deeply one breathes), which may occur with overuse or in people with pre-existing respiratory illness.
- Worsening of depression, a common condition in many people with insomnia.
- Residual daytime drowsiness, which is common with benzodiazepines. Long-acting benzodiazepines pose a higher risk than shorter-acting benzodiazepines.
- 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 older people and when taking long-acting formulations.
- In pregnant and nursing women, birth defects are a risk because these drugs cross the placenta and enter breast milk. Pregnant women or nursing mothers should not use these medications. Benzodiazepine use in the first trimester of pregnancy may be associated with the development of cleft lip in newborns.
- Although rare, fatal overdoses can occur.
Benzodiazepines are potentially dangerous when combined with alcohol. Some medications, like ulcer and acid reflux medications in the histamine receptor-2 blocker class (such as cimetidine, Tagamet), can slow the metabolism of the benzodiazepine.
Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 to 3 weeks after stopping the drug and may include:
- Gastrointestinal distress
- Disturbed heart rhythm
- Rebound insomnia (the risk is higher with short-acting benzodiazepines than with long-acting ones)
- In severe cases, hallucinations or seizures
Other Types of Sedative Hypnotics
Ramelteon (Rozerem, generic)
Ramelteon is a type of sedative hypnotic called a melatonin receptor agonist. Unlike non-benzodiazepines or benzodiazepines, which target GABA receptors, ramelteon works by targeting melatonin receptors. Ramelteon is not habit forming and is the first sleep drug that is not designated as a controlled substance. A related melatonin receptor agonist, tasimelteon (Hetlioz), is approved for treating circadian rhythm disorders in people who are blind.
In 2014, the FDA approved suvorexant (Belsomra), the first orexin receptor antagonist sleep drug. Suvorexant targets and blocks the action of orexin. Orexin (also called hypocretin) is a chemical produced in the hypothalamus part of the brain, which is involved in regulating the sleep-wake cycle and keeping people awake. Suvorexant is a controlled substance, which means it can potentially be abused or cause dependence. Like other sleep medications, suvorexant may cause sleep-related behaviors such as sleep driving. The FDA approved four different dose strengths for suvorexant and advises people to use the lowest effective dose.
Antidepressants are often helpful in treating insomnia even when anxiety or major depression are not present. Certain types of antidepressants with sedating properties are prescribed for the treatment of primary insomnia, generally in lower doses than used to treat depression.
For example, the antidepressant trazodone (Desyrel, generic) is prescribed in low doses as a hypnotic to help induce sleep. A very low dose formulation of the tricyclic antidepressant doxepin (Silenor) is approved for treatment of insomnia. Other antidepressants used for insomnia include the tricyclics trimipramine (Surmontil, generic) and amitriptyline (Elavil, generic) and the tetracyclic antidepressant mirtazapine (Remeron, generic).
Precautions should be taken in the use of trazodone and other sedating antidepressants in older people, due to the risk for side effects (daytime sleepiness, dizziness, priapism, and increased risk of falls) and drug interactions.
Similarly to benzodiazepines, barbiturates are central nervous system depressants that stimulate GABA receptors and thus inhibit nerve cells. Barbiturates were commonly used for insomnia treatment in the past, as well as for epilepsy, anxiety, and anesthesia, but have now been almost entirely replaced by newer, safer drugs in most regions of the world. A few barbiturates that are FDA-approved for the short treatment of insomnia are still marketed in the United States, including secobarbital (Seconal) and butabarbital (Butisol). These drugs are controlled substances and are rarely used today.