Am
J Psychiatry
136:10,
CLINICAL
October
AND
/979
RESEARCH
REPORTS
This section contains 1) nett’ research findings, including preliminary data from pilot studies, either clinical or laboratory; 2) t’ortht’hile replication studies; 3) (.() reports that describe a truly new syndrome or cast new light on established ones; and 4) case reports that indicate a neit’ therapeutic procedure ofpotential value or call attention to adverse effects of drugs or previously unreported cotnplications of therapeutic interventions. Program descriptions and literature reviett’s cannot be printed in this section. Criteriaforformat are listed in “Inf ormation for Contributors’ in each issue; papers that do not adhere to these criteria t’ill be returned to the author. ‘
Early BY
Onset GUY
ofTardive
Dyskinesia:
CHOUINARD,
M.D.,
Recent studies have occurs with alarming treated with neuroleptics cidence
oftardive
outpatients
M.SC.
sistent
with
the
drome
is called
with
(PHARMACOL),
among
AND
BARRY
of
(4), which
other
or tardive
surveys.
is con-
The
because
D. JONES,
syn-
it is usually
seen after several years of neuroleptic treatment. In this paper we describe a patient who developed tardive dyskinesia I month after his first exposure to neuroleptic drug treatment.
Results Case
Report
and
received
outpatient
psychotherapy
patient
discontinued
treatment
was
next
plaining
seen
in the
ofdelusional
emergency
fears
without
after room
about
medication.
a short 3 years
his health.
time later
The
mental
physician’s
and com-
stat-
us examination revealed blunted affect and some thought disorder in a clear sensorium. The patient was admitted to the hospital with a diagnosis of undifferentiated schizophrenia. He was considered to have a schizoid personality with a slow onset of illness. Mr. A had no history of psychotropic drug intake, drug abuse, alcoholism, or organic brain disorder, and no family Received
May
29, 1979; accepted
June
Marilyn
wish to thank Lawrence Annable, B.Sc. on the manuscript, and Ms. Barbara E. Levy for their assistance. 0002-953X/79/l
Dip. Stat. Lewis and
,
l/l323/02/$0O.35
,
and
laboratory
assessment
of
parkinsonism
and
movements, and a clinical global impression kinesia. The presence oftardive dyskinesia cording to a standard procedure described
tests
done
Table
I lists
the patient’s
scores
dyskinetic
of tardive was assessed previously
on the parkinsonism
dysac(4).
and
tardive dyskinesia scales. On day 0 the ESRS showed only a mild decrease of pendular arm movements, presumably a resuit ofthe medications Mr. A had received shortly before the study began. His dyskinesia rating was negative. On day 14
he had an ESRS ed bradykinesia,
and occasional The patient
score of 10 for parkinsonism, which includrigidity, and tremor in the upper limbs; tar-
complete was again
protrusion. rated on the
we first noticed his tardive ing neuroleptic drugs, and ing fluphenazine decanoate cyclidine, 5 mg p.o. t.i.d.
for Ms.
©
examination
dive dyskinesia was not present at this time. However, by day 28 Mr. A had developed definite slow lateral torsion movements of the tongue, with frequent partial protrusion
19, 1979.
Dr. Chouinard is Assistant Professor of Psychiatry, McGill University, and Psychiatrist and Pharmacologist, Research Department, H#{243}pitalLouis-H Lafontaine, 7401 rue Hochelaga, Montreal, Que., Canada H1N 3M5. Dr. Jones is Resident, Allan Memorial Institute, Department of Psychiatry, McGill University. The authors his comments
of physical
before the drug trial were normal. Extrapyramidal side effects were recorded on the Extrapyramidal Symptom Rating Scale (ESRS) (5) ofChouinard and Ross-Chouinard on day 0 and then weekly for the 4-week period. The ESRS consists of a subjective questionnaire of parkinsonian symptoms, a
Mr. A, a 23-year-old unemployed single man, first received psychiatric treatment in January 1975 for complaints of depression. He was thought to have depressive neurosis
The
M.D.
history of neurologic or psychiatric disorder. He was given tnfluoperazine, 2 mg p.o. t.i.d. for 3 days. This medication was stopped and the patient then entered a 4-week doubleblind controlled trial designed to compare pimozide and chlorpromazine. Mr. A was randomly assigned to chlorpromazine treatment and received I 50 mg p.o. b.i.d. under blind conditions. On day 10, the chlorpromazine dosage was increased to 300 mg p.o. b.i.d. because he had not shown significant therapeutic response. On day 14 procyclidine, an anticholinergic-antiparkinsonian drug, was added in a dosage ofs mg p.o. b.i.d. The patient continued on this regimen for the remainder of the trial.
261 schizophrenic
neuroleptics
results
late
Report
shown that tardive dyskinesia frequency among patients (1-3). We found a 31% in-
dyskinesia
treated
Case
1979
American
Psychiatric
ESRS
6 months
after
dyskinesia. He had been receivat the time of evaluation was takI.M. 25 mg every 3 weeks; pro; and flurazepam, 30 mg h.s. He
Association
I 323
CLINICAL
AND
RESEARCH
Am
REPORTS
1
TABLE
Patient’s
Scores on the Extrapyramidal
Symptom
Rating
Scale
Week Rating
0
2
4
examination)” Totalscore Hypokinesia
I I
10 6
3 1
7 3
10 6
Hyperkinesia
0
4
2
4
4
Parkinsonism
Tardive Total
dyskinesia” score
Bucco-linguo-masticatory
Upper
40 mg/day. was 6=most severe.
of 0-6:
showed
mild
rigidity
but had no signs formed, which
ated 2 weeks evaluation).
after The
decrease ofpendular and mild akathisia. more severe than dyskinesia movements, complete
given
4
0
6
0
4
0
4
0
0
0
2
this
of the arms
his injection parkinsonism
2 weeks
However,
also
after
(3 weeks
been
injection
procyclidine, was reevalu-
after the previous a mild
revealed
mild tremors
his tardive initially;
his
test was per-
except the The patient
examination
movements, it had
evaluation.
A procyclidine
kept constant to 40 mg/day.
of the tongue, with frequent partial protrusion. Dyskinetic were
0
0
after
of dyskinesia.
with all drugs was increased
extremities
31
0 0
extremities
Procyclidine, b5j
28
(physician’s
there
ofboth
arms,
dyskinesia was
was
moderate
definite slow lateral torsion protrusion, and occasional movements of the upper
October
1979
dive netic
dyskinesia movements
explains in our
the patient
disappearance 6 months
of after
the
dyskisyn-
drome was first observed. However, by increasing the antiparkinsonian drug dosage, we were able to uncover the tardive dyskinesia, which was more severe than it had been initially. This is understandable because the patient had had further exposure to neuroleptics. The uncovering of the dyskinesia with an antiparkinsonian dyskinesia.
The
possibility
patients relatively
the
agent
confirms
of tardive
the
dyskinesia
who have been taking short time contraindicates
treatment
of nonpsychotic
diagnosis
of
tardive
developing
neuroleptic drugs neuroleptic
patients.
We also
in for a use in
sug-
gest that an antiparkinsonian drug be given in the early stages of neuroleptic treatment in order to avoid the masking of tardive dyskinesia by hypokinetic parkinsonian symptoms. REFERENCES
Discussion
Tardive dyskinesia is usually observed in patients who have received several years of treatment (6). A very few cases have been reported after 6 months of drug treatment (7). In monkeys, the syndrome is known to appear in its complete form after 10 weeks of weekly neuroleptic treatment (8). The case we have described is to our knowledge the earliest reported onset of this disorder (I month after initiation of neuroleptic treatment). This early onset may be explained as follows: the patient manifested only mild hypokinetic symptoms of parkinsonism when the dyskinetic movements were first noted. These symptoms tend to cover tardive dyskinesia, as we found in a previous study of patients receiving long-term neuroleptic therapy. The dyskinetic patients tended to have fewer hypokinetic parkin-
1324
/36:/0,
of hypokinetic parkinsonian symptoms in our patient would have facilitated the early detection of his dyskinesia. The antiparkinsonian drug he received could also have contributed to the early emergence of dyskinetic movements. We have shown that antiparkinsonians may uncover tardive dyskinesia and that their effect is readily reversible (9). That antipsychotic drugs paradoxically cover tar-
noted.
sonian symptoms than oped tardive dyskinesia
J Psychiatry
patients who had not devel(4). Thus the relative absence
I. Bell RC, Smith RC: Tardive dyskinesia: characterization and prevalence in a statewide system. J Clin Psychiatry 39:39-42, 46-47, 1978 2. Jus A, Pineau R, Lachance R, et al: Epidemiology of tardive 3.
dyskinesia, part I. Dis Nerv Syst 37:210-214, 1976 Asnis GM, Leopold MA, Duvoisin RC, et al: A survey of tardive dyskinesia in psychiatric outpatients. Am J Psychiatry 134:1367-1370, 1977
4. Chouinard G, Annable L, Ross-Chouinard lated to tardive dyskinesia. Am J Psychiatry
A, et al: Factors re136:79-83, 1979
5.
A, et al:
6. 7.
8. 9.
Chouinard
G,
Annable
L,
Ross-Chouinard
Ethopropa-
zinc and benztropine in neuroleptic-induced parkinsonism. J Clin Psychiatry 40:147-152, 1979 Quitkin F, Rifkin A, Gochfeld L, et al: Tardive dyskinesia: are first signs reversible? Am J Psychiatry 134:84-87, 1977 Marsden CD, Tarsy D, Baldessarini RJ: Spontaneous and druginduced movement disorders in psychotic patients, in Psychiatnc Aspects of Neurologic Disease. Edited by Benson DF, Blumer D. New York, Grune & Stratton, 1975 Weiss B, Santelli 5: Dyskinesias evoked in monkeys by weekly administration of haloperidol. Science 200:799-801,1978 Chouinard G, de Montigny C, Annable L: Tardive dyskinesia and antiparkinsonian medication. Am J Psychiatry 136:228-229, 1979
J Psychiatry
136:10,
CLINICAL
October
AND
/979
RESEARCH
REPORTS
This section contains 1) nett’ research findings, including preliminary data from pilot studies, either clinical or laboratory; 2) t’ortht’hile replication studies; 3) (.() reports that describe a truly new syndrome or cast new light on established ones; and 4) case reports that indicate a neit’ therapeutic procedure ofpotential value or call attention to adverse effects of drugs or previously unreported cotnplications of therapeutic interventions. Program descriptions and literature reviett’s cannot be printed in this section. Criteriaforformat are listed in “Inf ormation for Contributors’ in each issue; papers that do not adhere to these criteria t’ill be returned to the author. ‘
Early BY
Onset GUY
ofTardive
Dyskinesia:
CHOUINARD,
M.D.,
Recent studies have occurs with alarming treated with neuroleptics cidence
oftardive
outpatients
M.SC.
sistent
with
the
drome
is called
with
(PHARMACOL),
among
AND
BARRY
of
(4), which
other
or tardive
surveys.
is con-
The
because
D. JONES,
syn-
it is usually
seen after several years of neuroleptic treatment. In this paper we describe a patient who developed tardive dyskinesia I month after his first exposure to neuroleptic drug treatment.
Results Case
Report
and
received
outpatient
psychotherapy
patient
discontinued
treatment
was
next
plaining
seen
in the
ofdelusional
emergency
fears
without
after room
about
medication.
a short 3 years
his health.
time later
The
mental
physician’s
and com-
stat-
us examination revealed blunted affect and some thought disorder in a clear sensorium. The patient was admitted to the hospital with a diagnosis of undifferentiated schizophrenia. He was considered to have a schizoid personality with a slow onset of illness. Mr. A had no history of psychotropic drug intake, drug abuse, alcoholism, or organic brain disorder, and no family Received
May
29, 1979; accepted
June
Marilyn
wish to thank Lawrence Annable, B.Sc. on the manuscript, and Ms. Barbara E. Levy for their assistance. 0002-953X/79/l
Dip. Stat. Lewis and
,
l/l323/02/$0O.35
,
and
laboratory
assessment
of
parkinsonism
and
movements, and a clinical global impression kinesia. The presence oftardive dyskinesia cording to a standard procedure described
tests
done
Table
I lists
the patient’s
scores
dyskinetic
of tardive was assessed previously
on the parkinsonism
dysac(4).
and
tardive dyskinesia scales. On day 0 the ESRS showed only a mild decrease of pendular arm movements, presumably a resuit ofthe medications Mr. A had received shortly before the study began. His dyskinesia rating was negative. On day 14
he had an ESRS ed bradykinesia,
and occasional The patient
score of 10 for parkinsonism, which includrigidity, and tremor in the upper limbs; tar-
complete was again
protrusion. rated on the
we first noticed his tardive ing neuroleptic drugs, and ing fluphenazine decanoate cyclidine, 5 mg p.o. t.i.d.
for Ms.
©
examination
dive dyskinesia was not present at this time. However, by day 28 Mr. A had developed definite slow lateral torsion movements of the tongue, with frequent partial protrusion
19, 1979.
Dr. Chouinard is Assistant Professor of Psychiatry, McGill University, and Psychiatrist and Pharmacologist, Research Department, H#{243}pitalLouis-H Lafontaine, 7401 rue Hochelaga, Montreal, Que., Canada H1N 3M5. Dr. Jones is Resident, Allan Memorial Institute, Department of Psychiatry, McGill University. The authors his comments
of physical
before the drug trial were normal. Extrapyramidal side effects were recorded on the Extrapyramidal Symptom Rating Scale (ESRS) (5) ofChouinard and Ross-Chouinard on day 0 and then weekly for the 4-week period. The ESRS consists of a subjective questionnaire of parkinsonian symptoms, a
Mr. A, a 23-year-old unemployed single man, first received psychiatric treatment in January 1975 for complaints of depression. He was thought to have depressive neurosis
The
M.D.
history of neurologic or psychiatric disorder. He was given tnfluoperazine, 2 mg p.o. t.i.d. for 3 days. This medication was stopped and the patient then entered a 4-week doubleblind controlled trial designed to compare pimozide and chlorpromazine. Mr. A was randomly assigned to chlorpromazine treatment and received I 50 mg p.o. b.i.d. under blind conditions. On day 10, the chlorpromazine dosage was increased to 300 mg p.o. b.i.d. because he had not shown significant therapeutic response. On day 14 procyclidine, an anticholinergic-antiparkinsonian drug, was added in a dosage ofs mg p.o. b.i.d. The patient continued on this regimen for the remainder of the trial.
261 schizophrenic
neuroleptics
results
late
Report
shown that tardive dyskinesia frequency among patients (1-3). We found a 31% in-
dyskinesia
treated
Case
1979
American
Psychiatric
ESRS
6 months
after
dyskinesia. He had been receivat the time of evaluation was takI.M. 25 mg every 3 weeks; pro; and flurazepam, 30 mg h.s. He
Association
I 323
CLINICAL
AND
RESEARCH
Am
REPORTS
1
TABLE
Patient’s
Scores on the Extrapyramidal
Symptom
Rating
Scale
Week Rating
0
2
4
examination)” Totalscore Hypokinesia
I I
10 6
3 1
7 3
10 6
Hyperkinesia
0
4
2
4
4
Parkinsonism
Tardive Total
dyskinesia” score
Bucco-linguo-masticatory
Upper
40 mg/day. was 6=most severe.
of 0-6:
showed
mild
rigidity
but had no signs formed, which
ated 2 weeks evaluation).
after The
decrease ofpendular and mild akathisia. more severe than dyskinesia movements, complete
given
4
0
6
0
4
0
4
0
0
0
2
this
of the arms
his injection parkinsonism
2 weeks
However,
also
after
(3 weeks
been
injection
procyclidine, was reevalu-
after the previous a mild
revealed
mild tremors
his tardive initially;
his
test was per-
except the The patient
examination
movements, it had
evaluation.
A procyclidine
kept constant to 40 mg/day.
of the tongue, with frequent partial protrusion. Dyskinetic were
0
0
after
of dyskinesia.
with all drugs was increased
extremities
31
0 0
extremities
Procyclidine, b5j
28
(physician’s
there
ofboth
arms,
dyskinesia was
was
moderate
definite slow lateral torsion protrusion, and occasional movements of the upper
October
1979
dive netic
dyskinesia movements
explains in our
the patient
disappearance 6 months
of after
the
dyskisyn-
drome was first observed. However, by increasing the antiparkinsonian drug dosage, we were able to uncover the tardive dyskinesia, which was more severe than it had been initially. This is understandable because the patient had had further exposure to neuroleptics. The uncovering of the dyskinesia with an antiparkinsonian dyskinesia.
The
possibility
patients relatively
the
agent
confirms
of tardive
the
dyskinesia
who have been taking short time contraindicates
treatment
of nonpsychotic
diagnosis
of
tardive
developing
neuroleptic drugs neuroleptic
patients.
We also
in for a use in
sug-
gest that an antiparkinsonian drug be given in the early stages of neuroleptic treatment in order to avoid the masking of tardive dyskinesia by hypokinetic parkinsonian symptoms. REFERENCES
Discussion
Tardive dyskinesia is usually observed in patients who have received several years of treatment (6). A very few cases have been reported after 6 months of drug treatment (7). In monkeys, the syndrome is known to appear in its complete form after 10 weeks of weekly neuroleptic treatment (8). The case we have described is to our knowledge the earliest reported onset of this disorder (I month after initiation of neuroleptic treatment). This early onset may be explained as follows: the patient manifested only mild hypokinetic symptoms of parkinsonism when the dyskinetic movements were first noted. These symptoms tend to cover tardive dyskinesia, as we found in a previous study of patients receiving long-term neuroleptic therapy. The dyskinetic patients tended to have fewer hypokinetic parkin-
1324
/36:/0,
of hypokinetic parkinsonian symptoms in our patient would have facilitated the early detection of his dyskinesia. The antiparkinsonian drug he received could also have contributed to the early emergence of dyskinetic movements. We have shown that antiparkinsonians may uncover tardive dyskinesia and that their effect is readily reversible (9). That antipsychotic drugs paradoxically cover tar-
noted.
sonian symptoms than oped tardive dyskinesia
J Psychiatry
patients who had not devel(4). Thus the relative absence
I. Bell RC, Smith RC: Tardive dyskinesia: characterization and prevalence in a statewide system. J Clin Psychiatry 39:39-42, 46-47, 1978 2. Jus A, Pineau R, Lachance R, et al: Epidemiology of tardive 3.
dyskinesia, part I. Dis Nerv Syst 37:210-214, 1976 Asnis GM, Leopold MA, Duvoisin RC, et al: A survey of tardive dyskinesia in psychiatric outpatients. Am J Psychiatry 134:1367-1370, 1977
4. Chouinard G, Annable L, Ross-Chouinard lated to tardive dyskinesia. Am J Psychiatry
A, et al: Factors re136:79-83, 1979
5.
A, et al:
6. 7.
8. 9.
Chouinard
G,
Annable
L,
Ross-Chouinard
Ethopropa-
zinc and benztropine in neuroleptic-induced parkinsonism. J Clin Psychiatry 40:147-152, 1979 Quitkin F, Rifkin A, Gochfeld L, et al: Tardive dyskinesia: are first signs reversible? Am J Psychiatry 134:84-87, 1977 Marsden CD, Tarsy D, Baldessarini RJ: Spontaneous and druginduced movement disorders in psychotic patients, in Psychiatnc Aspects of Neurologic Disease. Edited by Benson DF, Blumer D. New York, Grune & Stratton, 1975 Weiss B, Santelli 5: Dyskinesias evoked in monkeys by weekly administration of haloperidol. Science 200:799-801,1978 Chouinard G, de Montigny C, Annable L: Tardive dyskinesia and antiparkinsonian medication. Am J Psychiatry 136:228-229, 1979
