Antihistamines make you sleepy by antagonizing central histimine-1 (H-1) receptors in the brain. The ones you see in over-the-counter sleep aids are usually diphenhydramine and hydroxyzine. (There are other types of antihistamines that affect H-2, H-3, and H-4 receptors.) People build up tolerance to them over time and when they stop taking them experience rebound insomnia.
Also called histamine antagonists, antihistamines are administered to fight allergic reactions, in which cases sleepiness is considered a possibly undesirable side effect. For people who need to get to sleep, however, the drowsiness is the main benefit of antihistamines. These are usually not prescription drugs and can be purchased at retailers over-the-counter. They do, however, have the potential for negative effects if taken with other drugs, so let your doctor know if you are taking more than one medication.
Types of Antihistamines
Doxylamine can be used by itself as a sleep aid or combined with other drugs for cold and allergy relief (usually in a night-time formula). It is sometimes used along with Vitamin B6 to stop morning sickness during pregnancy. Doxylamine is one of the most powerful OTC sedatives in the U.S., more so than some prescription hypnotic drugs. Many patients taking doxylamine encounter dry mouth, nausea, and drowsiness.
Diphenhydramine was the first antihistamine approved by the FDA (in the 1940s) and is widely used in OTC sleeping pills. Many generic sleep aids consist solely of one active ingredient – diphenhydramine. It is one of the oldest antihistamines available (classified as a first-generation antihistamine), but for many patients surpasses the efficacy of even new prescription drugs. Medical professionals seek out diphenhydramine when a substantial histamine release demands a fast, effective reversal, and is therefore often the drug of choice for allergic rhinitis, motion sickness, insect bites and stings, and hives. Profound drowsiness is a very common side effect, as is dizziness, difficulty concentrating, and urinary retention.
Hydroxyzine is used for allergies and to suppress nausea. It is usually not appropriate for use just as a sleep aid.
Triprolidine is used in Europe and has a shorter half-life than some antihistamines, but there it is not often used in the US for insomnia.
Niaprazine was invented in France, and is used mainly in the European Union. The main use for niaprazine is its intense sedative effect (as opposed to its antihistamine effects). Vertigo and daytime sedation are frequently encountered with the use of this drug.
Pyribenzamine is another first-generation antihistamine; today it is used much less frequently as newer antihistamines arrive on the market. It is indicated for the treatment of hay fever, asthma, urticaria, and rhinitis, and is a mild sedative. Pyribenzamine is known to be abused recreationally with the opiate pentazocine. Common side effects of pyribenzamine use are dry mouth, nausea, gastrointestinal irritation, and dizziness.
Clemastine is indicated for the treatment of allergy symptoms, including rhinitis and pruritus (itching or hives). Although it is a sedative antihistamine, its effects are less intense than many other drugs of this nature. The side effects of clemastine are greatly dependent on the dose, and sometimes can produce contradictory responses. The most commonly reported side effects of clemastine use are dizziness, drowsiness, blurred vision, and dry mouth.
The Use of Antihistamines
Antihistamines are often the first sleep medication insomniacs take, and they are often sufficient. They do not require a doctor’s prescription. The regulatory authorities have decided they are safe enough that responsible adults can use them unsupervised.
Like all sleep medications, antihistamines artificially modify a person’s sleep patterns. They sometimes leave people groggy the next day, and the subjective quality of sleep is sometimes less than natural sleep. However, some feel the trade-off to stop insomnia is worth it. There is also the possibility of drug resistance where the body adapts to the antihistimine and it doesn’t work as well. And like other hypnotics, the long-term effectiveness of antihistamines has not been demonstrated in a manner that would satisfy scientists. Which doesn’t mean they don’t work, only the official science is still agnostic on the matter.
Doctors frequently recommend antihistamines over common prescription sleep aids when the patient has insomnia because of drug and alcohol withdrawal. This strategy is thought to reduce the risk of cross dependence. Be sure to run this idea by your doctor, though, because there is a risk and you should avoid mixing sleeping pills and other substances.
Tylenol PM® also uses an antihistimine to induce drowsiness. It also includes acetaminophen, the pain reliever in regular Tylenol. If you take a medicine like this to help you sleep, be aware of the pain reliever in the pill. Some people want an analgesic mixed in with their antihistimine, but if you do not, look for antihistimine sleep aids with no pain reliever. There are plenty at your local drug store.
Brain signals needed to keep us awake include histaminergic signals. The H-1 antihistamines block those signals and make us sleepy. Some antihistamines can cross the blood-brain barrier and get to the relevant receptors. These, like diphenhydramine, are useful as sedatives. Other antihistamines do not readily cross the barrier to the brain and are of use in medical applications where drowsiness is undesirable.
Somaxon Pharamaceuticals introduced the old tricyclic antidepressant drug doxepin under the brand name Silenor in 2011. In addition to effects on serotonin and norepinephrine, doxepin appears to have anti-histamine properties. This drug, under the brand name Sinequan, was prescribed off-label for insomnia in the past. Under the new name Silenor it is being marketed explicitly for sleep disorders.
During an allergic reaction, action at the histamine receptor sites causes a multitude of body responses. Antihistamines compete for the histamine receptor sites (most commonly H1-receptor sites) in order to block histamine, thus stopping or lessening the allergic reaction. Antihistamines are usually components of over-the-counter (OTC) allergy and sleeping pills such as Benadryl® or Unisom®.