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Antianxiety and sleeping medications
diazepam (Valium), chlordiazepoxide (Librium), alprazolam (Xanax), flurazepam
(Dalmane)
Almost all of the central nervous system depressants have antianxiety properties and can
be used as tranquilizers. This is true of alcohol, barbiturates, etc. Similarly, these
same drugs all have sedative properties and can be used as a sleeping pill. Antianxiety
medications are sometimes referred to as "minor tranquilizers" to distinguish
them from the antipsychotic medications which are sometimes called "major
tranquilizers". These are terrible names and should be abandoned. The "minor
tranquilizers" are extremely effective and not at all "minor". "Major
tranquilizers" are sedating and therefore have some tranquilizing properties, but are
more accurately labeled antipsychotic medication. Antianxiety medications are also
referred to as anxiolytic. Sleeping pills are referred to as hypnotics.
The more useful tranquilizers are those that have the largest antianxiety effects with the
least sedation. The benzodiazepines have largely supplanted older drugs in this class such
as the barbiturates. This class of medication includes diazepam (Valium), chlordiazepoxide
(Librium), alprazolam (Xanax), flurazepam (Dalmane) and many others. Benzodiazepines are
much safer and less addicting than these older drugs. The new medication buspirone appears
to be even safer and less addicting than the benzodiazepines and in the future may replace
them for some uses, although there is some strong suggestion that it is less effective.
Sedating antihistamines such as diphenhydramine (Benadryl) can also be used as either an
antianxiety medication or as a sleeping pill, although it is less effective and has more
side effects than the benzodiazepines.
The major difference between whether a benzodiazepine is considered to be a tranquilizer
or sleeping pill is how it is marketed and advertised. There are some clinically important
differences in how fast the medications begin to act, and how long they last. A sedating
medication that acts rapidly is likely to be a more effective sleeping pill than one that
acts more gradually. In addition, alprazolam (Xanax) and clonazepam (Klonopin) also seem
to have antipanic and mood stabilizing properties not shared by the other benzodiazepines.
Despite these difference the benzodiazepines are much more like each other than different.
Buspirone (Buspar) is a new anti-anxiety medication that is the first of a new class.
Unlike the benzodiaepines, burspirone has anti-anxiety effects without being sedating.
The benzodiazepines, barbiturates and many of the other meds used as sleeping pills or
antianxiety medications are subject to abuse and can be addicting. These addicting drugs
are all at least partially cross tolerant (an addicted individual can replace one drug
within this class with another), and the withdrawal of an addicted individual is much more
medically dangerous than heroin withdrawal. Abruptly stopping the use of meds in someone
who is addicted to alcohol, barbiturates, or diazepam (Valium) can result in a life
threatening convulsions. If addiction to any of these drugs is a possibility in a
consumer, meds for a gradual detoxification should be prescribed, and hospital admission
may be necessary to control drug use. The sedating antihistamines (eg. diphenhydramine
[Benadryl]) are subject to abuse, but are not physiologically addicting and are not cross
tolerant with the others. Buspiron (BuSpar) seems to be neither subject to abuse nor
addicting.
A. Benzodiazepines eg. diazepam (Valium), chlordiazepoxide (Librium), alprazolam (Xanax),
flurazepam (Dalmane): The usual drug of choice when a minor tranquilizer is indicated is
one of the drugs in this class.
1. Clinical indication: The benzodiazepines are most commonly used as antianxiety
medications. They are relatively safe drug that are difficult (but possible) to kill
yourself with unless combined with alcohol. They have anticonvulsant properties-clonazepam
(Klonopin) is regularly used as an anticonvulsant, and diazepam (Valium) can be used
intravenously to stop a seizure. If a consumer must be sedated (in those very rare
instances) before you know what is going on in a new consumer who might have amphetamines
or other street drugs on board, a benzodiazepine such as diazepam or lorazepam may be a
safer drug to give than an antipsychotic medication such as Thorazine or Haldol. Some of
the benzodiazepines (eg. alprazolam [Xanax] and clonazepam [Klonopin]) have antipanic and
mood stabilizing properties.
As with all medications, the benzodiazepines should not be used without a reason and
should not be continued without a reason for continuation.
2. Side Effects of Benzodiazepines:
a. All of the benzodiazepines are clearly addictive, but to put things into perspective
diazepam (Valium) is less addicting and certainly less dangerous than alcohol. The short
acting benzodiazepines (e.g. alprazolam, Xanax) are more addicting than the longer acting
drugs in the same class. Drugs with a "kick" caused by their rapid onset of
action such as Valium seem somewhat more subject to abuse than drugs with a more gradual
onset such as Librium. Anyone who has been taking these medications for more than a few
days should have his meds decreased slowly rather than abruptly discontinued. Serious, at
times life threatening seizures from abrupt withdraw have been reported with all of the
benzodiazepines, but is more of a problem with short acting than long acting drugs. A
gradual withdrawal is safer, and will also help to minimize the inevitable discomfort that
accompanies withdrawal.
b. All of the benzodiazepines may cause drowsiness (which usually improves after a few
days of use). All of these drugs also cause more or less of an intoxication, similar to
alcohol, with impaired judgment, decreased coordination, light headiness, etc. Consumers
should be warned about using machinery or driving cars, especially when getting used to
these drugs. Recent research has suggested that even consumers well adjusted to small
doses of these medications have a measurable impairment in their driving ability. These
effects wear off more quickly with short acting drugs, and stay around much longer with
the longer acting drugs which can actually build up over time if taken daily
c. The benzodiazepine can sometimes unleash otherwise inhibited violent behavior. Again,
this "disinhibition" is similar to what one sometimes sees with alcohol
intoxication.
d. All of these drugs can interfere with memory. This seems to be a particular problems
with triazolam (Halcion) and the other short acting drugs, and a particular problem with
older consumers who might already have some memory impairment.
e. It has been suggested that these drugs might increase birth defects when taken by
pregnant women. Recent reviews have found no evidence of increased birth defect with these
drugs, but to be safe they should be avoided, especially during the first three months of
pregnancy.
3. Doseage recommendations for Benzodiazepines:
a. As an antianxiety medication, diazepam (Valium) is commonly prescribed in 5 or 10 mg
tablets up to 40 mg/day. Chlordiazepoxide (Librium) is usually prescribed in doses of
10-25 mg. up to 100 mg. a day. When alprazolam (Xanax) is used as an antianxiety
medication a typical dose range would be 1-4 mg/day given in divided doses. When
alprazolam is used as an antipanic medication, is is often necessary to use significantly
higher dose. In most cases, when these medication are used as antianxiety medications
their use should be restricted to short term, i.e., 1-2 weeks for crises or periods of
extreme stress. Chronic use has its place, but only rarely and usually in consumers with
significant functional disability. Consumers should be warned not to drive or use
machinery at work until they know how the dosage affects them.
b. As a detoxification agent in consumers addicted to other depressant drugs, larger doses
of Valium or Librium will be needed with the dosage changing as the consumer's clinical
condition changes. In alcohol withdrawal, the use of 50 mg of Librium every two hours is
not uncommon. Do not add insult to injury by giving diazepam to someone who is still
intoxicated with alcohol or barbiturates. At times, someone who is used to chronically
having a high blood alcohol level can go into withdrawal while they still have alcohol in
their blood, as long as the blood alcohol level is significantly less than what they have
become tolerant too. These people can be in in active withdrawal despite the presence of
alcohol in their blood, and a benzodiazepine may be indicated to treat this withdrawal.
c. In an acutely out of control consumer for whom a good history and diagnosis is not
available who must be controlled with drugs (for whom restraints are not enough for some
reason) and who might be using street drugs, diazepam 10-20 mg P.O. may be safer than
Thorazine (start low and work up if that is possible). Consumers with schizophrenia or
mania who are both acutely psychotic and out of control can often be sedated with a
combination of an antipsychotic medication and a benzodiazepine. This combination will
help reestablish control with a lower dose of antipsychotic medication than would
otherwise be necessary, and often with concomitant fewer side effects.
Diazepam is absorbed faster and more completely by mouth than by intramuscular injection,
so it should be given by pill rather than intramuscular injection. If a very fast response
is required in an emergency situation, lorazepam (Ativan) 2-4mg can be taken by injection.
Street drugs are commonly cut with scopolamine or a similar anticholinergic drug that is
made worse by Thorazine, and the street drug PCP or Angel Dust can have serious lethal
interactions with Thorazine.
4. Considerations of which benzodiazepine to use: In general, the major differences among
different benzodiazepines are the speed of onset of action, and how long the drug effects
last (half-life or time it takes for the body to eliminate 50% of the drug). These
duration effects are very different if the drugs are used very occasionally, or used
daily. In the occasional user Valium is a short acting drug, but in the chronic user it is
a very long acting drug. Oxazepam (Serax) seems to have a shorter duration of action than
most of the others (shorter elimination half-life). Dalmane has a rapid onset and a long
half-life, so although it is sold as a sleeping pill, it has significant anxiolytic
(tranquilizing) action the next day or two. Both Valium and Librium have moderately long
half-lives.
Alprazolam (Xanax) and clonazepam (Klonopin) are different from the other benzodiazepines
in that they appear to have mood stabilizing properties, and are as effective in
spontaneous panic attacks as are antidepressants. Clonazepam (Klonopin) is a long acting,
sedating benzodiazepine that is commonly used as an anticonvulsant, and may have mood
stabilizing properties as well.
Common Benzodiazepines
Half-Life (Hr) Daily Dosage Addiction Range(mg) Potential
alprazolam (Xanax) 12-29 0.5-4 Higher
chlordiazepoxide (Librium)12-48 25-100 Lower
clonazepam (Klonopin) 19-60 2-8 Lower
diazepam (Valium) 20-90 2-40 Higher
flurazepam (Dalmane) 24-100 15-30 Moderate
lorazepam (Ativan) 0-20 1-4 Higher
oxazepam (Serax) 8-21 30-60 Lower
temazepam (Restoril) 12-24 15-30 Moderate
B. Buspirone (BuSpar)
This is an entirely new class of drug that works through an entirely different mechanism
of action than either the benzodiazepines or other sedative/hypnotics. It appears to be
non-addictive, not habit forming and not subject to abuse (so far). It is the first drug
to be anxiolytic without being at all sedating. It does not appear to make consumers more
sensitive to the effects of alcohol or other sedating drugs. It is not a muscle relaxant,
and has no anticonvulsant properties. It is also not useful in helping with alcohol or
other drug withdraw.
It does appear to have a few idiosyncrasies which may limit its use in some consumers.
While Valium and the other benzodiazepines appear to work almost immediately after
consumers take their first pill, buspirone must be used regularly for up to several weeks
before it is fully effective. This means it is best used as a regular medication for
someone who can tolerate a delay before it begins working, rather than as a medication
that can be taken episodically with rapid effects as with Valium type drugs. A second
issue has to do with its effectiveness. Double blind research studies have concluded that
BuSpar is as effective as Valium when used by anxious subjects who have never previously
used Valium. For some reason, consumers who have previously had much experience with
Valium or Valium type drugs often feel that BuSpar is less effective. There are at least
two possible interpretations to these research findings. One is that the use of Valium
type drugs produces long lasting biological changes in one's brain that makes the BuSpar
less effective, and the other is that BuSpar is not really quite as effective as Valium
but that it works "good enough" for most people unless they have already
experienced the very powerful and immediate effects of Valium type drugs.
Even with limited experience, BuSpar seems particularly useful for consumers who are
potential drug abusers, and consumers who do not like or cannot tolerate the sedative side
effects of benzodiazepines.
C. Sleeping Pills (Hypnotics)
Many consumers who complain of insomnia are already sleeping an adequate amount, but feel
that they "should" be sleeping more or are so bored that they want to sleep more
to fill up time. Other consumers are concerned that they cannot sleep at night, but are
taking naps during the day and the problem is the structure of the sleep cycle, rather
than a lack of sleep. Other consumers are depressed, and the insomnia usually improves
when the depression is treated. In addition, some consumers with insomnia have a specific
sleep disorder such as sleep apnea. There are specific treatments for some of these
disorders, and sleeping pills may actually make things worse.
Sleeping pills are frequently necessary in the hospital because of the noise and
strangeness of the hospital and general anxiety of the consumer. They should never be
taken automatically, however. They should never be used in a newly admitted consumer who
is still intoxicated (with alcohol or some other depressant) or who still has the obvious
after-effects of a recent overdose. They should be used with caution in older consumers
who are likely to become confused, disoriented and on rare occasions can get a terrifying
transient organic psychosis from sleeping pills. Finally, consumers with severe
respiratory diseases are more prone to serious medical complications from the respiratory
depressant side effects of most of the meds we use and especially sleeping pills.
When I prescribe sleeping pills for an outconsumer, I rarely give more than five pills at
a time. It is sometimes nice to have a sleeping pill in the medicine closet for especially
bad nights, but it is rarely necessary for anyone to use sleeping pills on a regular
basis. Often, the problems caused by sleeping pills are worse than the problems caused by
poor sleep.
I do NOT use or prescribe barbiturates (eg. secobarbital [Seconal]). They are more
dangerous and more addicting. Triazolam (Halcion) used to be preferred because of its
short half-life and lack of accumulation, especially in the elderly. The concern that
triazolam may cause more memory impairment than other medications has led me to be
cautious about its use. Tolerance develops to all of these medications (with the possible
exception of zolpidem). That is, all of these medications are less effective in someone
used to taking a lot of sleeping pills or tranquilizers every day.
1. Flurazepam (Dalmane): very similar to diazepam (Valium) with all of its side effects
and advantages. It is possible but difficult to kill yourself with an overdose of this
drug and it usually provides a comfortable night's sleep with minimum hangover. It is a
very long acting medication however, with a half-life of from 47-100 hours. This tends to
be longer in older people. This means that half of the medication can still be in your
body, four days after you take one pill. If a consumer uses flurazepam every night, the
dose from one night is added to the remaining medication from previous nights. This
accumulation when flurazepam is taken every night is an particular problem in elderly
consumers who can easily become confused or appear demented as the serum level of
flurazepam increases. The usual dose is 15 mg before bedtime.
2. Temazepam (Restoril): This is a short acting benzodiazepine that is both safe and
effective. The relatively short half-life means that the medication does not accumulate
from one night to the next as does flurazepam. The usual does is 15 mg before bedtime.
3. Chloral hydrate: this is an old favorite that has long been used because of its
relative safety from side effects. It is a more dangerous drug to overdose on than
flurazepam. It has a shorter half-life of 7-10 hours, so dose accumulation is less of a
problem than with flurazepam. Unfortunately, consumers become habituated to chloral
hydrate fairly rapidly, so that after a few days it often becomes less effective. Usual
dose 500 mg before bed in older people, 1000 mg. before bed in young healthy adults with
an additional 500mg an hour later if the consumer still cannot sleep.
4. Diphenhydramine (Benadryl): This is a sedating antihistamine that can be used as a
safe, mild sleeping medication The biggest problem with diphenhydramine are its
anticholinergic side effects (dry mouth, blurred vision, constipation). More importantly,
anticholinergic medications like diphenhydramine can also cause confusion, especially in
the elderly or in consumers who are already taking other anticholinergic medications
(including many of the antidepressants or antipsychotic medications). Diphenhydramine has
already been mentioned as a treatment for muscular side effects from antipsychotic meds.
The usual dose is 50-100 mg. before bed, with instructions that the consumer may repeat
that dose in one hour. Other sedating antihistamines are also available, including
hydroxyzine (Vistaril)
5. Zolpidem (Ambien). This is a new sleeping pill that seems to have a similar but
slightly different mechanism of action than the benzodiazepines. It is reported to be
highly effective, non-addicting and with few side effects. Early research suggests that
unlike the other sleeping pills, tolerance does not develop to zolpidem. It is important
to remember that the benzodiazepines were also reported to be non-addicting when they were
first introduced, and the particular abuse potential of aprazolam was not initially
recognized. At the same time, zolipem may have some real advantage over other sleeping
pills in the few situations where a sleeping pill is indicated. 10mg is a typical dose for
a healthy adult, and 5mg is a typical geriatric dose.
This material was created by Ronald J Diamond, M.D.
University of Wisconsin Department of Psychiatry
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