CLINICAL
AND
Diazepam
RESEARCH
Withdrawal
BY MARK
L.
DE
Am
REPORTS
Syndrome:
BARD,
A Case
with
into clinical use in 1963, diazenonaddicting. However, for
years
been
literature
has
sprinkled
with
reports
to
the contrary. Phenobarbital was also initially thought to be safe and free of addictive properties until accumulated clinical experience over many years proved otherwise (1). Amphetamine, introduced clinically in 1935, was not realized Numerous authors
to be addictive until about have warned ofthe existence
1958. of a
diazepam withdrawal syndrome (1-3). At least 8 cases ofacute organic brain syndrome thought to be secondany to withdrawal ofdiazepam have been described (4, 5). Thirteen cases of grand mal withdrawal seizures have been reported (3-9). One case of prolonged coma following diazepam withdrawal was found (10). I will describe a case that combined an acute organic brain syndrome instances, along
and prolonged with a grand
stance, in a patient diazepam. Case
The patient, him
could
not
be withdrawn
from
to be much
he had he
cluded
seemed
had
The
mental
apathetic,
during
obvious
status
withdrawn, ideation.
showed
His
was
8 days
depression . All prehospital medicawith the exception of diazepam, and
started.
and preoccupied, numbness
Over cinations
started
and and
perspiring,
staring
and
seizure
comatose
for the next
contacted
and
patient
improved
over
admission,
he
the
became
behavior.
suddenly
workup the
was
had a grand normal.
6 hours.
following
had been
He
His previous
history
taking
was
next
week.
despondent
He complained
became very unsteady on his 2 days, the patient experienced disorientation. He became
complete
The
He
after
with
the next
of
feet.
Feb.
6, 1978;
revised
that
admission
the patient
he
had
reportedly
never
devel-
During the next 9 days the diazepam dosage was gradually decreased and then stopped. Imipramine was restarted. Ten days later, he began to show the same withdrawal symptoms and became comatose, with frequent jerking movements.
He was given diazepam, but and
he remained no response
S mg I.M. The twitching
deeply comatose, to pain. He was
5 mg I.M.
S weeks
on diazepam, problems.
mal seizure. remained
A
deeply
physician
was
obtained.
diazepam,
80 mg/day,
Aug.
30,
1978;
accepted
Sept.
from
20,
Dr. Dc Bard is Director, Department of Emergency Services, Greene Memorial Hospital, 1 141 North Monroe Dr. , Xenia, Ohio 45385. He is also Clinical Instructor, Department of Family Practice, Wright State University Medical School, and a staffmember at St. Elizabeth Medical Center in Dayton, Ohio, where this work was performed.
0002-953X178/0
I/0104/02/$00.35
not
Two
and
flaccid extremities a second dose
later
he had
food. He improved over a normal mental status. dose of 5 mg q.i.d.
after
admission.
follow-up
for
stopped,
with given
hours
He
has
I 1 months
The occurrence of a diazepam without precedent. Such
,
of
awakened the next 18 Diazepam and he was
been
maintained
showed
no further
© 1979
withdrawal convulsions
curred 2-12 days after discontinuation tion, with an average of8 days.
The
persistence
similar therapy
times
of coma
case I am for tetanus
and
diazepam effect
1978.
104
after
and
status.
the
aware (10).
coma. that
This
would
not
received
has
is very
One might say this from acute psychotic
unusual;
resolution seem
patient’s depression
the
within
only
hours this
to be a very
much
medica-
after high-dose ofcoma three
to confirm
seem
seizure is have oc-
of the
of occurred The occurrence
dramatic
administration
drawal
visual halluvery restless,
1969 through 1973. In 1973 he had an elective medical hospitalization. The diazepam was discontinued during this hospitalization, but no other medications were changed. He was Received
Ten days
then,
oped seizures and lapsed into coma for an unknown length of time. A neurosurgeon gave him intravenous diazepam. Over the next 24 hours the patient’s sensorium cleared and he recovered completely. He was discharged with the diagnosis of acute brain syndrome secondary to diazepam withdrawal and was maintained on diazepam, 10 mg q.i.d. Based on this information, the patient was given diazepam, S mg I.M. Several hours later he was sufficiently alert to take diazepam orally, 5 mg every 8 hours. Over the next 24 hours he began eating and returned to a normal mental
history of epilepsy and this was con-
firmed by his relatives for the 3 weeks that he stayed with them before his admission. The patient was admitted to the psychiatric unit with the
imipramine
1979
Comment
The patient gave no personal or family or seizures. He used alcohol only socially,
However,
January
Coma
given tricyclic antidepressants a seizure to that point.
discharged
and depressed 2 weeks earlier, medications in-
an examination
suicidal
exam
10 mg q.i.d.
diagnosis of involutional tions were continued
and
enough to request some hours and again attained was given in a maintenance
man, was seen in the emergency
gesture. more
diazepam,
not had
diazepam,
a 56-year-old
for a suicide
than and
who
coma in three separate mal seizure in one in-
Report
room
Seizure,
136:1,
M.D.
Since its introduction pam has been considered the
Psychosis,
J Psychiatry
medical
of
as with-
important attention.
mental changes or even from
resulted the anti-
cholinergic effects of imipramine. However, the temponal relationships do not favor these interpretations, and imipramine was not given the first time the patient
underwent
withdrawal.
The
recurrence
of the
same
mental symptoms three times 8-10 days after discontinuation of diazepam firmly supports the diagnosis of acute organic brain syndrome secondary to drug withdrawal. Discussion
It has been almost 15 years since the introduction of diazepam, and its addictive potential is just beginning to be realized. A physical dependence seems to develAmerican
Psychiatric
Association
Am
J Psychiatry
op
in some
basis
136:1,
January
patients
(probably
who
1979
use
a minimum
CLINICAL
the
drug
on
of 2 weeks).
withdrawal symptoms seem to be associated longer period of use and higher doses, but marked individual variation. For many years it has been said that the state’
many
‘
pam isjust Maletzky such
people
experience
that
between
recurrence the more
I have
are
no longer
‘
1. Covi
a is
one
dependence
to identify.
should
of even refrain
of diazepam for longer patient. Similarly, one
discontinue have been
diazepam long-term
on
treatment and/or
from
than a should
for pahigh-dose
therapy.
Panic
Attacks:
BY STEPHEN AND MARY
There
are
Diagnostic
F. PARISER, E. FONTANA,
growing
Evaluations
M.D., M.D.
numbers
BRUCE
M.D.,
EMIL
on anxiety-
panic syndromes and their relationship to cardiovascuIan disorders such as hyperdynamic beta-adnenergic states and mitral valve prolapse syndromes (MVPS) (1-3). We recently reported on a case involving an association between panic disorders and MVPS (1). Panic attacks have also been noted to occur in affective disorders (depression) (4).
Treatment cal
community
of panic .
attacks
Tricyclic
has challenged
antidepressants,
the mcdimonoamine
oxidase (MAO) inhibitors, beta-blocking agents, and psychotherapy have all been reported effective to some degree in treating patients with panic attacks (57). Recent changes in psychiatric nosology have encounaged specific treatment in specific syndromes by way ofexclusion-inclusion criteria. The draft third cdition of the Diagnostic and Statistical Manual of Mental Disorders (8) incorporates a variety of syndromes, referred to as anxiety disorders, all associated with Received
Aug.
4, 1978;
accepted
Oct.
R.
JH,
and
et al: Length
response
to
their
of treatment sudden
Dr. Pariser is Assistant Professor of Psychiatry and Family Mcdicine and Instructor of Obstetrics and Gynecology, Ohio State University College of Medicine, 456 Clinic Dr., Columbus, Ohio 43210, where Dr. Jones is Assistant Professor and Coordinator of Residency Training, Dr. Pinta is Assistant Professor, and Dr. Young is Clinical Instructor, Department of Psychiatry; and Dr. Fontana is Associate Professor, Division of Cardiology, Department of Mcdicine. © 1979
PINTA,
M.D.,
ELIZABETH
with
withdrawal.
A. YOUNG,
one or more types of anxiety symptoms. these diagnostic categories requires that inquire as to the This is important
ferentiate lated
presence or absence because there
patients
with
different
Anxiety
symptoms activity
Anxiety
Proper use of the physician
of panic a need
forms
are related
and
attacks. to dif-
of anxiety-re-
symptoms
to autonomic
to cognitive-affective
(panic
raise
questions
their
relationship
their
about
the
to cardiac
nervous functioning.
or other
signs of any number of disorders. patients whose chief complaint
and
is
M.D.,
symptoms.
system
symptoms)
can
be
Our work focuses is panic attacks.
etiology and
of panic psychiatric
on We
attacks, disorders,
treatment.
Method
and
Subjects
The subjects were adult patients of the psychiatrist authors (S.F.P. E.A.Y.) during a 6-month period plaint of panic attack symptoms. tients,
5, 1978.
0002-953X/78/01/0105/02/$00.35
S. Pattison
sedatives
of 17 Patients
A. JONES,
of reports
REPORTS
Acta Psychiatr Scand 49:51-64, 1973 2. Bant W: Diazepam withdrawal symptoms. Br Med J 2:285, 1975 3. Maletzky BM, Klotter J: Addiction to diazepam. mt J Addict 11:95-115, 1976 4. Barten HH: Toxic psychosis with transient dysmnestic syndrome following withdrawal from Valium. AM J Psychiatry 121:1210-1211, 1965 5. Preskorn SH, Denner Li: Benzodiazepines and withdrawal psychosis. .JAMA 237:36-38, 1977 6. Hollister LE (ed): Valium: a discussion of current issues. Psychosomatics 18:1-15, 1977 7. Hollister LE, Motzenbecker FP, Degan RO: Withdrawal reactions from chiordiazepoxide (“Librium”). Psychopharmacologia 2:63-68, 1961 8. Rilkin A, Quitkin F, Klein DF: Withdrawal reaction to diazepam. JAMA 236:2172-2173, 1976 9. Vyas I, Carney MWP: Diazepam withdrawal fits. Br Med J 2:44, 1975 10. Kendall Mi, Clarke SW: Prolonged coma alter tetanus. Br Med i 1:354-355, 1972
‘anxiety diaze-
development
L, Lipman
anxiolytic
state (3, 6). feasibility of
difficult
the
dependence,
outpatient prescription month in any individual not abruptly tients who
with there
stop
physiologic
to prevent
physical
severe
of patients’ original symptoms. severe symptoms of withdrawal
described
In conclusion, minor
they
a return to their premedication and Klotten (3) question the
a distinction
and the Certainly,
after
RESEARCH
REFERENCES
a chronic
More
AND
1 1 men
and
13 women,
who
,
who consulted one B.A.J. E.R.P. or with a chief cornThere were 24 pa,
had
panic
,
attacks
diagnosed by the Research Diagnostic Criteria (9). Their ages ranged from 21 to 53 years. All were interviewed by a psychiatrist. Because of the nature of their symptoms, cardiology evaluation, echocardiogram, and thyroid studies (T3, T4, and FTI) were requested. Seven patients did not complete the full evaluation. We will
report
American
here
on
Psychiatric
the
17 patients
Association
who
completed
the
105
AND
Diazepam
RESEARCH
Withdrawal
BY MARK
L.
DE
Am
REPORTS
Syndrome:
BARD,
A Case
with
into clinical use in 1963, diazenonaddicting. However, for
years
been
literature
has
sprinkled
with
reports
to
the contrary. Phenobarbital was also initially thought to be safe and free of addictive properties until accumulated clinical experience over many years proved otherwise (1). Amphetamine, introduced clinically in 1935, was not realized Numerous authors
to be addictive until about have warned ofthe existence
1958. of a
diazepam withdrawal syndrome (1-3). At least 8 cases ofacute organic brain syndrome thought to be secondany to withdrawal ofdiazepam have been described (4, 5). Thirteen cases of grand mal withdrawal seizures have been reported (3-9). One case of prolonged coma following diazepam withdrawal was found (10). I will describe a case that combined an acute organic brain syndrome instances, along
and prolonged with a grand
stance, in a patient diazepam. Case
The patient, him
could
not
be withdrawn
from
to be much
he had he
cluded
seemed
had
The
mental
apathetic,
during
obvious
status
withdrawn, ideation.
showed
His
was
8 days
depression . All prehospital medicawith the exception of diazepam, and
started.
and preoccupied, numbness
Over cinations
started
and and
perspiring,
staring
and
seizure
comatose
for the next
contacted
and
patient
improved
over
admission,
he
the
became
behavior.
suddenly
workup the
was
had a grand normal.
6 hours.
following
had been
He
His previous
history
taking
was
next
week.
despondent
He complained
became very unsteady on his 2 days, the patient experienced disorientation. He became
complete
The
He
after
with
the next
of
feet.
Feb.
6, 1978;
revised
that
admission
the patient
he
had
reportedly
never
devel-
During the next 9 days the diazepam dosage was gradually decreased and then stopped. Imipramine was restarted. Ten days later, he began to show the same withdrawal symptoms and became comatose, with frequent jerking movements.
He was given diazepam, but and
he remained no response
S mg I.M. The twitching
deeply comatose, to pain. He was
5 mg I.M.
S weeks
on diazepam, problems.
mal seizure. remained
A
deeply
physician
was
obtained.
diazepam,
80 mg/day,
Aug.
30,
1978;
accepted
Sept.
from
20,
Dr. Dc Bard is Director, Department of Emergency Services, Greene Memorial Hospital, 1 141 North Monroe Dr. , Xenia, Ohio 45385. He is also Clinical Instructor, Department of Family Practice, Wright State University Medical School, and a staffmember at St. Elizabeth Medical Center in Dayton, Ohio, where this work was performed.
0002-953X178/0
I/0104/02/$00.35
not
Two
and
flaccid extremities a second dose
later
he had
food. He improved over a normal mental status. dose of 5 mg q.i.d.
after
admission.
follow-up
for
stopped,
with given
hours
He
has
I 1 months
The occurrence of a diazepam without precedent. Such
,
of
awakened the next 18 Diazepam and he was
been
maintained
showed
no further
© 1979
withdrawal convulsions
curred 2-12 days after discontinuation tion, with an average of8 days.
The
persistence
similar therapy
times
of coma
case I am for tetanus
and
diazepam effect
1978.
104
after
and
status.
the
aware (10).
coma. that
This
would
not
received
has
is very
One might say this from acute psychotic
unusual;
resolution seem
patient’s depression
the
within
only
hours this
to be a very
much
medica-
after high-dose ofcoma three
to confirm
seem
seizure is have oc-
of the
of occurred The occurrence
dramatic
administration
drawal
visual halluvery restless,
1969 through 1973. In 1973 he had an elective medical hospitalization. The diazepam was discontinued during this hospitalization, but no other medications were changed. He was Received
Ten days
then,
oped seizures and lapsed into coma for an unknown length of time. A neurosurgeon gave him intravenous diazepam. Over the next 24 hours the patient’s sensorium cleared and he recovered completely. He was discharged with the diagnosis of acute brain syndrome secondary to diazepam withdrawal and was maintained on diazepam, 10 mg q.i.d. Based on this information, the patient was given diazepam, S mg I.M. Several hours later he was sufficiently alert to take diazepam orally, 5 mg every 8 hours. Over the next 24 hours he began eating and returned to a normal mental
history of epilepsy and this was con-
firmed by his relatives for the 3 weeks that he stayed with them before his admission. The patient was admitted to the psychiatric unit with the
imipramine
1979
Comment
The patient gave no personal or family or seizures. He used alcohol only socially,
However,
January
Coma
given tricyclic antidepressants a seizure to that point.
discharged
and depressed 2 weeks earlier, medications in-
an examination
suicidal
exam
10 mg q.i.d.
diagnosis of involutional tions were continued
and
enough to request some hours and again attained was given in a maintenance
man, was seen in the emergency
gesture. more
diazepam,
not had
diazepam,
a 56-year-old
for a suicide
than and
who
coma in three separate mal seizure in one in-
Report
room
Seizure,
136:1,
M.D.
Since its introduction pam has been considered the
Psychosis,
J Psychiatry
medical
of
as with-
important attention.
mental changes or even from
resulted the anti-
cholinergic effects of imipramine. However, the temponal relationships do not favor these interpretations, and imipramine was not given the first time the patient
underwent
withdrawal.
The
recurrence
of the
same
mental symptoms three times 8-10 days after discontinuation of diazepam firmly supports the diagnosis of acute organic brain syndrome secondary to drug withdrawal. Discussion
It has been almost 15 years since the introduction of diazepam, and its addictive potential is just beginning to be realized. A physical dependence seems to develAmerican
Psychiatric
Association
Am
J Psychiatry
op
in some
basis
136:1,
January
patients
(probably
who
1979
use
a minimum
CLINICAL
the
drug
on
of 2 weeks).
withdrawal symptoms seem to be associated longer period of use and higher doses, but marked individual variation. For many years it has been said that the state’
many
‘
pam isjust Maletzky such
people
experience
that
between
recurrence the more
I have
are
no longer
‘
1. Covi
a is
one
dependence
to identify.
should
of even refrain
of diazepam for longer patient. Similarly, one
discontinue have been
diazepam long-term
on
treatment and/or
from
than a should
for pahigh-dose
therapy.
Panic
Attacks:
BY STEPHEN AND MARY
There
are
Diagnostic
F. PARISER, E. FONTANA,
growing
Evaluations
M.D., M.D.
numbers
BRUCE
M.D.,
EMIL
on anxiety-
panic syndromes and their relationship to cardiovascuIan disorders such as hyperdynamic beta-adnenergic states and mitral valve prolapse syndromes (MVPS) (1-3). We recently reported on a case involving an association between panic disorders and MVPS (1). Panic attacks have also been noted to occur in affective disorders (depression) (4).
Treatment cal
community
of panic .
attacks
Tricyclic
has challenged
antidepressants,
the mcdimonoamine
oxidase (MAO) inhibitors, beta-blocking agents, and psychotherapy have all been reported effective to some degree in treating patients with panic attacks (57). Recent changes in psychiatric nosology have encounaged specific treatment in specific syndromes by way ofexclusion-inclusion criteria. The draft third cdition of the Diagnostic and Statistical Manual of Mental Disorders (8) incorporates a variety of syndromes, referred to as anxiety disorders, all associated with Received
Aug.
4, 1978;
accepted
Oct.
R.
JH,
and
et al: Length
response
to
their
of treatment sudden
Dr. Pariser is Assistant Professor of Psychiatry and Family Mcdicine and Instructor of Obstetrics and Gynecology, Ohio State University College of Medicine, 456 Clinic Dr., Columbus, Ohio 43210, where Dr. Jones is Assistant Professor and Coordinator of Residency Training, Dr. Pinta is Assistant Professor, and Dr. Young is Clinical Instructor, Department of Psychiatry; and Dr. Fontana is Associate Professor, Division of Cardiology, Department of Mcdicine. © 1979
PINTA,
M.D.,
ELIZABETH
with
withdrawal.
A. YOUNG,
one or more types of anxiety symptoms. these diagnostic categories requires that inquire as to the This is important
ferentiate lated
presence or absence because there
patients
with
different
Anxiety
symptoms activity
Anxiety
Proper use of the physician
of panic a need
forms
are related
and
attacks. to dif-
of anxiety-re-
symptoms
to autonomic
to cognitive-affective
(panic
raise
questions
their
relationship
their
about
the
to cardiac
nervous functioning.
or other
signs of any number of disorders. patients whose chief complaint
and
is
M.D.,
symptoms.
system
symptoms)
can
be
Our work focuses is panic attacks.
etiology and
of panic psychiatric
on We
attacks, disorders,
treatment.
Method
and
Subjects
The subjects were adult patients of the psychiatrist authors (S.F.P. E.A.Y.) during a 6-month period plaint of panic attack symptoms. tients,
5, 1978.
0002-953X/78/01/0105/02/$00.35
S. Pattison
sedatives
of 17 Patients
A. JONES,
of reports
REPORTS
Acta Psychiatr Scand 49:51-64, 1973 2. Bant W: Diazepam withdrawal symptoms. Br Med J 2:285, 1975 3. Maletzky BM, Klotter J: Addiction to diazepam. mt J Addict 11:95-115, 1976 4. Barten HH: Toxic psychosis with transient dysmnestic syndrome following withdrawal from Valium. AM J Psychiatry 121:1210-1211, 1965 5. Preskorn SH, Denner Li: Benzodiazepines and withdrawal psychosis. .JAMA 237:36-38, 1977 6. Hollister LE (ed): Valium: a discussion of current issues. Psychosomatics 18:1-15, 1977 7. Hollister LE, Motzenbecker FP, Degan RO: Withdrawal reactions from chiordiazepoxide (“Librium”). Psychopharmacologia 2:63-68, 1961 8. Rilkin A, Quitkin F, Klein DF: Withdrawal reaction to diazepam. JAMA 236:2172-2173, 1976 9. Vyas I, Carney MWP: Diazepam withdrawal fits. Br Med J 2:44, 1975 10. Kendall Mi, Clarke SW: Prolonged coma alter tetanus. Br Med i 1:354-355, 1972
‘anxiety diaze-
development
L, Lipman
anxiolytic
state (3, 6). feasibility of
difficult
the
dependence,
outpatient prescription month in any individual not abruptly tients who
with there
stop
physiologic
to prevent
physical
severe
of patients’ original symptoms. severe symptoms of withdrawal
described
In conclusion, minor
they
a return to their premedication and Klotten (3) question the
a distinction
and the Certainly,
after
RESEARCH
REFERENCES
a chronic
More
AND
1 1 men
and
13 women,
who
,
who consulted one B.A.J. E.R.P. or with a chief cornThere were 24 pa,
had
panic
,
attacks
diagnosed by the Research Diagnostic Criteria (9). Their ages ranged from 21 to 53 years. All were interviewed by a psychiatrist. Because of the nature of their symptoms, cardiology evaluation, echocardiogram, and thyroid studies (T3, T4, and FTI) were requested. Seven patients did not complete the full evaluation. We will
report
American
here
on
Psychiatric
the
17 patients
Association
who
completed
the
105
