Sleep Disorders

Benzodiazepines

The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsant, amnestic and muscle relaxant properties. The more scientific name is benzodiazepine receptor agonists (BzRAs). Benzodiazepines are often used for short-term relief of severe, disabling anxiety or insomnia. Long-term use can cause problems because patients develop tolerance and become dependent. These drugs are believed to act on the GABA receptor GABAA, the activation of which dampens higher neuronal activity. They "nonselectively" target the GABA receptor sites and this nonselectivity is one of the marks against benzodiazepines in treatment of insomnia, especially since the development of more targeted drugs.

They began to be widely prescribed for stress-related ailments in the 1960s and 1970s. They are still used as anti-anxiety drugs (e.g. Xanax). Short-acting benzodiazepines are still often used by travelers to reduce the effects of jet lag.

Benzodiazepines differ from each other in duration of action and pharmacokinetics. Liver disease has less effect on the metabolism of lorazepam, oxazepam, and temazepam than on the metabolism of other benzodiazepines. Whereas long-acting agents may produce daytime hangover, short-acting agents are more often associated with dependence, rebound insomnia, early morning insomnia, daytime anxiety, and serious withdrawal effects, such as seizures. The following general characterizations can be made:

Intermediate- and short-acting benzodiazepines are characterized by half-lives of 4 to 24 hours.
Short-acting benzodiazepines are characterized by the following:
- Few active metabolites.
- Rarely, accumulation with multiple doses.
- Minimal effect on drug clearance by age and liver disease.
Long-acting benzodiazepines are characterized by the following:
- Half-lives of longer than 24 hours.
- Pharmacologically active metabolites.
- Accumulation with multiple dosages.
- Impaired clearance in older patients and those with liver disease.

In the past (the 70s and 80s) benzodiazepines were the most commonly prescribed sleep drugs in the United States.

Common benzodiazepines

flurazepam (Dalmane)

clonazepam (Klonopin)

quazepam (Doral)

triazolam (Halcion)

lorazepam (Ativan)

alprazolam (Xanax)

estazolam (ProSom)

flunitrazepam (Rohypnol)

temazepam (Restoril)

oxazepam (Serax)

prazepam (Centrax)

Benzodiazepines are potentially dangerous when used in combination with alcohol. You sometimes here of people overdosing and dying or requiring medical attention when mixing these drugs. Some presciption medications can slow the metabolism of the benzodiazepine.

Side Effects

Side effects may differ depending on whether the benzodiazepine is long- or shorting acting. They include:

* 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.

Withdrawal Symptoms

Withdrawal symptoms usually occur after prolonged use and can last one to three weeks after stopping the drug and may include the following:

Gastrointestinal distress
Sweating
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, 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.