0022.3YW90 $3.00 + .OO IFS1990 Pergamon Pros plc

J ~sych,ol. Rex. Vol. 24, Suppl. 2, pp. 121-127, 1990 Printed m Great Britain.

BENZODIAZEPINES

AND ALCOHOL

MARKKU I. LJNNOILA NationalInstitute on Alcohol Abuse and Alcoholism, Bethesda. MD 20X92. U.S.A. Summary-The frequency and quantity of alcohol consumption is a major consideration in patients who need treatment with benzodiazepinej. Alcohol affects the GABA-ben/.odiarepine-chloride ionophore complex and has an agonist-like action. Thuh, additive interactions should be expected from combining alcohol with benzodiaaepines. Furthermore, alcohol has clinically meaningful anxmlytic efficacy. and many anxious patients may take advantage of that fact. Therefore, co-administration of alcohol and henrodiazepines is to be expected in an anxious patient receiving benrodiaLepmea who doe\ not totally abstain from alcohol. Thi\ article reviews three clmically relevant isues concerning benLodiazepines and alcohol: (I) interactions of ben/odiarepinea with social drinking in patients taking benrodiaLepines for indications unrelated to alcoholism: (2) use of henzodiaLepines in treatment of alcohol withdrawal: and (3) use of hen7odiaxpines m patients with alcohol dependence.

INTRODUCTION SHORT review elucidates three clinically relevant issues concerning benzodiazepines and alcohol: 1. Interactions of benzodiazepines with socially used quantities of alcohol in patients taking benzodiazepines for indications unrelated to alcoholism; 2. Benzodiazepines in treatment of alcohol withdrawal: and 3. Use of benzodiazepines in patients with alcohol dependence. This review is derived from six recent overviews written by investigators from Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism (LINNOILA, 1983; LINNOILA, 1984a; LINNOILA, 1984b; LINNOILA, 1987: NUTT et ul., 1989). These overviews should be consulted for a complete list of references. THIS

INTERACTIONS

OF BENZODIAZEPINES

WITH

ALCOHOL

Despite the fact that recent studies have documented superior long-term efficacy of antidepressants over benzodiazepines in the treatment of anxiety disorders. benzodiazepines still are widely prescribed for these disorders. Alcohol, a widely used social emollient with a non-specific mechanism of action, affects the GABA-benzodiazepine-chloride ionophore complex. Its net effect is an agonist-like action. Thus, additive interactions are to be expected from combining alcohol with benzodiazepines. Furthermore, alcohol acutely has clinically meaningful anxiolytic efficacy, and many anxious patients have taken advantage of this fact. Therefore, co-administration of alcohol and benzodiazepines is to be expected in any anxious

Address Alcoholism,

correspondence LCS.

DICBR,

to Markku Building

Linnoila. IO, Room

M.D., 3Bl9.9000

Ph.D.,

National

Rockville,

Institute MD

20892.

on Alcohol U.S.A.

Abuse

and

patient

receiving

clinician’s

duty

evaluation.

This

insomnia.

benzodiazepines to carefully is particularly

needs treatment patient’s

frequency

amounts

of alcohol

benzodiazepines relatively

low propensity

the market

in the United

be buspirone. administered

in patients

a relevant

of alcohol

with

alcohol.

patient

disorders.

and they should

to produce

It is the

presenting

for

depression.

and

a non-benzodiat.epine

anxiolytic

a benzodiazepine

Patients

warned

about

who often

additive

be treated with

adverse

SLICK

fact in choosing

Two

adverse

such drugs

oxaLepam.

and

A useful

that is free of additive

even

effects

of

that has a currently

on

alternative

may

adverse effects

Because these three drug\ have not been shown

the treatment of panic attacks. they should

is the

COI~SLI~W

a ben/odiazepine

interactions.

States are chlordiazepoxide

with alcohol.

from

of any

anxiety

consumption.

have to be clearly

and alcohol.

abstain

habits

that a patient i\ not dependent on or abusing alcohol and

benzodiazepines,

and quantity

not totally

are common to patients with alcohol dependence.

has determined

with

does

the drinking

important

because these complaints

Once the physician

small

who

explore

when

to be efficacious

not be used when panic symptoms

in

are a part of a

patient’s complaints.

BENZOI~IAZEPINES

Two

pathophysiological

Ih’ THt

‘f’KEATMf’.NT

characteristics

hypothalamic-pituitary-adrenocortical

Of= ALCOHOL.

of alcohol

overactivity.

WITHIIKAWAI

withdrawal.

respond

well

noradrenergic

to benzodiaLepines,

~lncl

u hich

are the current treatment of choice of this condition. Controlled such

studies

have demonstrated

as chlorpromazine

benzodiaLepines tremens.

can also

Although

effective

pharmacological

currently

situations.

intervention.

of ethanol

use in the United

in moderate withdrawal

Oral diazepam

which time a loading dose should be instituted,

or the symptoms

with

in severe withdrawal

procedure

diaLepam

initially

IO mg every

sedated. If withdrawal re-evaluated symptoms

for

dosing. this

symptoms

illnesses.

additional

Careful

doses

eliminatin,

permits

a withdrawal

hourly

six

20

nrg.

01.

dons.

evaluations

of diaTepam

arc treated orally

the patient the patients

should

becomes

should

continue.

up IO every

bc

and if

6 h. should

loading dose. very few patients require

relatively

symptoms.

administration

in nauseated patients.

Chlordia/.epoxidr

at

be

additional

seekinc c bcbavior. Because dia/epam and it\ active have long half-lives (33 and 50 h on average. respectively),

of withdrawal

dia7epam. although

25

(7 drug

desmethyldiazepam.

regimen

increase in severity.

Patients

are suppressed

reduced following

Once treated with the initial

thereby

metaholite.

until

need

subside.

by NAKANJO et trl. ( 19%).

is not sufficiently

co-existing

reappear.

administered.

hour

trequently

and ct’fectively trcatctl according to a dia/epam

can be safely

described

States

may offer

IO mg or oral chlordia/.epoxide

until either the symptoms

Patients

one

The

delirium

and

withdrawal.

mg every 0 h as required may be administered

loading

withdrawal.

seizures

available for clinical

Patients

over other drugs

of alcohol

and treat withdrawal

in the treatment

advantages over another in specific

of benLodia/.epincs

in the treatment

be used to prevent

the benxodiazepines

all appear to be equally only minimal

the superiority

and hydroxy/ine

Dia;lepam

has a duration

free of drug-induced

is also available

of action

md

it is absorbed more slowly.

“high”

a\ an intravenous

metabolic pathway roughly A similar

regimen

md

rc-emergence

preparation similar

as descrihcd

for rapid to that of

for, dia/.epam.

BEMODIAZEPINES

AND

123

ALCOHOL

however, can be followed using chlordiazepoxide 2.5 mg instead of diazepam 10 mg. Oxazepam and lorazepam have shorter half-lives (8 h and 10 h on average, respectively) than diazepam and chlordiazepoxide, and should therefore be administered every 6 h (oxazepam 15-60 mg, lorazepam 1-3 mg). Tapering of either lorazepam or oxazepam should begin on the second day, decreasing approximately lS-25% from the initial daily dose every day. Tapering should be accomplished by decreasing the dose, not by increasing the interval between doses. Lorazepam may also be administered intra-muscularly or sub-lingually in nauseated patients. The benzodiazepines have similar side effects. Memory impairment is common, although often subtle. Impairment will frequently be sufficiently severe, however, to interfere with rehabilitation attempted during the first several days of hospitalization. Minor cardiovascular and respiratory depression may occur with high doses, although this is unusual when benzodiazepines are administered alone. Because they have an additive interaction in combination with ethanol, caution must be exerted when benzodiazepines are administered for the treatment of ethanol withdrawal before the blood alcohol concentration reaches zero. Diazepam has been reported to inhibit the gag reflex, thus increasing the risk of aspiration in nauseated patients. Symptoms of benzodiazepine overdose such as excessive drowsiness. lethargy, alaxia, diplopia, and confusion are similar to those observed with ethanol intoxication. USE OF BENZODIAZEPINES

IN TREATMENT

OF PATIENTS

WITH ALCOHOL

DEPENDENCE

Diagnostic considerutions Adoption studies by CLONINGERet al. (1988) have defined two genetically distinct forms of alcoholism called Type I and Type II. Type 1 is the more common form of the illness. It affected 75% of men alcoholics and all women alcoholics in the sample investigated. For the genetic predisposition to be expressed, a man who is at risk needs to be exposed to an adverse environment. Women may express the gene effect also without environmental provocation. Type II alcoholism afflicts only men. Approximately 25% of alcoholic men have this disorder. It is inherited from fathers to sons, but not to daughters, and the gene effect is expressed without environmental provocation. Excessive consumption of alcohol starts at an early age and anti-social personality disorder and criminality co-exist with alcoholism in the families. Women with the genetic background often have symptoms of somatization. Patients with Type II alcoholism are unlikely to benefit from benzodiazepines. Indeed, these drugs are relatively contraindicated in such patients, particularly if they exhibit impulsive behaviors, which may be aggravated by benzodiazepines. If psychotropics are indicated in Type II alcoholics to treat symptoms such as poor impulse control and dysthymia, medications such as carbamazepine and lithium probably are preferable. However, no controlled studies are available on pharmacological treatment of Type II alcoholism with or without other mental disorders. Type I alcoholics free of other mental disorders may not benefit from any pharmacotherapy. Patients with Type I alcoholism who exhibit symptoms or have a history of other mental disorders should be divided into primary and secondary alcoholics depending on the relative times of onset of alcoholism and other mental disorders. Patients with primary Type I alcoholism and secondary mental disorder other than alcoholism need to maintain abstinence, and the secondary mental disorder needs to be treated vigorously. Successful treatment of

alcoholism

as such may reduce

Patients

with

treatment

secondary

of the primary

mental

The issue of alcoholics in choosing

to be actively

block

therapeutically

Anxiety.

and

pharmacotherapy

and than

of anxiety

attacks.

alcohol

alcoholism

with

hut

needs to be considered and

abstinence alcohol

may

disorders

are

more

of the population. on a careful

common

The

among

approach

differential

to the

diagnosis

of

because

treatment

of panic

for

panic

alcoholics

patients

relationship

disorder

well

with

between

associated

have

v, ith panic

reported

are probably

to tricyclic

I .3 benzodin/-epines

of the rccenlly patient

amine

mild additive adverse

following

among

than the

panic

panic

attacks

attacks

and

been thought

attacks.

efficacies

monoamine

~triti-deprcs~lrnts

and

to be effective

onlv

111

thi5 concept

may

hc

However.

of clonazcpam

oxida\c

(TCA\)

and

lora~epam

in the

attack:s.

then secondary

beverages

The

alw respond

anxiety

If an alci)hol-deperldent

inhibitor\.

common

may he that certain

anxiety.

of choice

patients

anticipatory

are more

explanation

be complex.

The conventional

changing

‘WA\

eff’ects

M ith panic

bvith alcohol

the;< do not produce should

attack\

are probably

on psychomotor

cstastrophiz

an alcoholic

is dctcrmincd

the treatment

rc!apse

with

g during

to pre\ent

a suicide

tlmp

Thcye

performance.

interactions lo drinkin

not

oi‘choicc.

have oni)

Furthermore.

tyraminc drug

unlike

containing

treatment

food4

and

\top

dic1 res(rictions.

According trestmcnt

to preliminary

of panic

in heav!

thev. mav. become

phobia\ treatment

pharniacotherapy. be avoided

not produce

reup:akc

drinking

they

behavioral

serotonin

These drugs do not product

bnsi\.

Social

reduce

reports.

disorder.

Thu\.

difficulty

The

to drinking.

of psychotropics.

deficit depends

disorder.

to encourage

use of psychotropics

the rest

agoraphobia.

anticipatory

the treamientb

inhibitors,

alleviating

should

mental

the risk of relapse

measures

effects

attention

The simplest

may, however.

alpra/olam.

and

concomitant

among

disorder.

to medications

Furthermore.

in alcoholics

and without

to alleviate

In general. (MAO)

MAO

to reduce

risk of addiction

pharmacological

families

mental

for the primary

disorders.

Panic

risk.

is expected

because

affective.

rest of the population. drink

at a high

be treated

pharmacotherapy.

necessary

their

of the secondary

should

disorder

promoted,

eating.

alcoholics anxiety

being

appropriate

need

symptoms

alcoholism

can

\(lcial

the :reatment

bc ~ucce~~t‘~~lIy

program In patients

involvin with

drinkers.

of choice

treated

alcoholism

dependence. in maintaining

If beta-blockers \obricty,

a drug.

with

hcta-blocker\

mav

be effective

and

social

dependcncc. are

LISU~