Benzodiazepines receptor agonists (BzRAs) are a group of prescription drugs that slow down the body’s central nervous system (CNS). They are considered to be minor tranquilizers, and are often used before certain medical procedures; especially endoscopies and dental work. Sometimes they are used to neutralize the anxiety-related symptoms that may accompany the initial use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. BzRA potentiate the effects of GABA, but have little direct effect on other neurotransmitters.
Modern sleep pharmacology can be traced to the 1960s when benzodiazepine receptor agonists (informally called benzodiazepines) were introduced. The old barbiturate drugs were too dangerous. The effective dose to lethal dose ratio was too high. Benzodiazepines (sometimes called in the scientific literature, BzRAs) have a much lower ratio and very rarely led to fatal overdoses. The early BzRAs lasted too long for optimal insomnia treatment, producing sleep inertia in the patient. New ones were developed with shorted half lives: triazolem, midazolem.
Types of Benzodiazepines
Temazepam is a benzodiazepine used primarily as a sleeping pill. In the 1980s it was widely prescribed for insomnia. With the development of the Z-drugs, it is rarely prescribed any more, although there may be situations where doctors find it useful. Sold under the brand name Restoril, temazepam has the same effects as other benzodiazepines – reduce anxiety, muscle relaxation, sometimes amnesia.
The half-life of Temazepam is approximately 10 hours (varies from person to person), making it appropriate for treatment of sleep maintenance insomnia. It is less useful for sleep onset insomnia. There is a significant risk of dependence for people taking temazepam. You shouldn’t take it more than a few weeks. The Z-drugs tend to be less addictive. People frequently have withdrawal symptoms when coming off temazepam.
Lormetazepam (C16H12Cl2N2O2) is a benzodiazepine that can be used for insomnia. It is not available for sale in U.S. pharmacies. Scientific evidence shows this drug is inferior to others on the market for treatment of insomnia.
Loprazolam (brand name Dormonoct or Havlane) is a benzodiapine used for severe insomnia. It is pretty powerful and not appropriate for most people with sleep disorders when other drugs will work for them. * The major disadvantage is the long half-life, which causes the patient to experience daytime sleepiness or trouble getting up the day after swallowing the pill. It also has the side effects of other benzodiazepines and cannot be used over long period because of addition
Flurazepam (brand name Dalmane) is another benzodiazepine medicine once used for insomnia, but now largely discouraged because of its long half life results in daytime sedation. The long half-life means the patient may not experience an improvement in their insomnia the first night, but will see benefits in the second or third nights.
Alprazolam is used to treat anxiety, panic disorders, depression, and premenstrual syndrome. Pfizer manufactures alprazolam in the U.S. under the brand name Xanax®. Alprazolam is rarely used to treat insomnia. Its most common side effects are drowsiness and dizziness.
Clonazepam is in the class of “highly potent” benzodiazepines, although its sedative effects are less powerful when compared with similar drugs. It is commonly used to treat epilepsy, anxiety disorders, restless legs syndrome, chronic fatigue syndrome, and panic attacks. It is also used to remediate the effects of some antipsychotic medications used with schizophrenia. Users of clonazepam report experiencing drowsiness, impaired cognition, impaired coordination and balance, and dizziness. As many as 30% of patients treated on an extended basis develop “low-dose dependence.” Clonazepam is sold as Klonopin® in the U.S. by Roche.
Diazepam is more commonly known in the United States as Valium®, produced by Roche. It is used to treat a broad spectrum of conditions, and is listed in the World Health Organization’s Essential Drug List as a core medicine. Although diazepam is approved to treat anxiety, panic attacks, and insomnia (short-term), many of its uses are off-label; including tetanus, mania, alcohol and opiate withdrawal, spastic muscle paresis, and as pre- or post-operative sedation. Frequent side effects include impaired motor function, anterograde amnesia, and depression.
Valium is one of the most well-known drugs of the 20th Century, and the most used prescription drug in the US between 1969 and 1980. 2.3 billion pills were dispensed in the peak year of 1978.
Flunitrazepam is considered to be one of the most addictive benzodiazepines, and its effects are estimated to be 7-10 times more powerful than diazepam. It is currently considered to be an illegal drug in the United States and is not approved for medical use. Flunitrazepam is marketed in many other countries by Roche as Rohypnol®. Its use produces many side effects, among them drowsiness, loss of motor control, amnesia, slurred speech, and confusion. Flunitrazepam has an extensive history as a recreational and date-rape drug.
Lorazepam is marketed by Wyeth Pharmaceuticals as Ativan® in the United States. It is indicated for the treatment of anxiety disorders, short-term insomnia (especially when it is associated with anxiety), acute delirium, several types of epilepsy, and as a pre-medication to decrease the quantity of an anesthetic required before a surgical procedure. It is also used to combat the nausea and vomiting associated with chemotherapy. Lorazepam is considered to be highly addictive, and is most often used as a short-term treatment. It produces such side effects as blurred vision, drowsiness, dizziness, and orthostatic hypotension (a sudden drop in blood pressure when transitioning from lying to sitting or from sitting to standing).
Nitrazepam is a strong hypnotic drug, and is most often used to alleviate insomnia (short-term). It is sometimes used for the management of seizures. Initial research indicated that nitrazepam produces significant euphoria, and is likely to become habit-forming if used for extended periods. Common reported side effects are fatigue, drowsiness, loss of coordination, vertigo, dizziness, confusion, and headache. Roche manufactures nitrazepam and it is sold in the U.S. as Mogadon®.
Oxazepam is primarily used to treat anxiety and alcohol withdrawal. It is also used to treat insomnia where the individual has difficulty staying asleep. Oxazepam produces many common side effects: drowsiness, dry mouth, dizziness, fatigue, weakness, and diarrhea. Manufacturer Actavis discontinued oxazepam (trade name Serax®) in the United States in 2006.
Triazolam was briefly removed from several international markets due to concerns regarding the side effects produced with high dosages of the drug. At lower doses, the Food and Drug Administration has declared it safe for use. It is approved for the treatment of insomnia (including jet lag) and as a sedative. Triazolam users have described headache, drowsiness, daytime sedation, and lethargy as common reactions. In the U.S., triazolam is marketed as Halcion® by Pfizer.
Estazolam is still used for insomnia under the brand name ProSom. It is considered an intermediate half life drug, and peak blood plasma concentration is generally a few hours after the patient swallows the pill. More info here.
These are prescription drugs for a reason. Use them only under doctor supervision. For insomnia, the newer Z-drugs are usually prescribed, although doctors may choose a benzodiazepine if there are other illnesses or physiological phenomena involved. Chronic abuse of benzodiazepines and the related change in sleep architecture can lead to an inability to be fully awake during the day. There is also new evidence that long-term use of benzodiazepines can increase the risk of neurodegenerative disorders such as Alzheimer’s