193
Original Articles
Psychosis and Other
Psychiatric Manifestations
of Levodopa Therapy
Gastone G. Celesia, MD, and
Arlene N. Barr, MD, Madison, Wis
IN RECENT years levodopa has proved
to be the most effective agent presently avail-
able for the treatment of parkinsonism.1-6u
Among the side effects of levodopa therapy,
psychiatric disturbances have been noted.3-6
Levodopa is not only the precursor of
dopamine hydrochloride but also of norepi-
nephrine.7 Although the action of these two
catecholamines upon the central nervous
system is incompletely understood, evidence
has been accumulated in the last two de-
cades upon their action in behavior.8,9 In this
context we would like to report 16 cases of
psychiatric disturbances which occurred
among 45 patients treated with levodopa.
Method
Levodopa was administered to 45 patients
(31 men and 14 women) with Parkinson's syn-
drome. Forty-one patients had primary par-
kinsonism or Parkinson's disease, three had
postencephalitic parkinsonism, and one had
arteriosclerotic parkinsonism. Of the patients
willing to enter the program, only those with
decompensated cardiovascular disease, renal
disease, psychosis, and moderate to severe de-
mentia were rejected. The detailed results of
Accepted for publication April 21, 1970.
From the Department of Neurology, University of
Wisconsin Medical Center, and Veterans Adminis-
tration Hospital, Madison, Wis.
Reprint requests to Department of Neurology,
University of Wisconsin Medical School, Madison,
Wis 53706 (Dr. Celesia).
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levodopa treatment of these 45 patients will be
published separately. Here we want to describe
the 16 patients who developed psychic phenom-
ena during the levodopa trial.
Levodopa was administered orally in tablets
of 250 and/or 500 mg. After an initial test done
of 250 mg, patients received 1,000 mg of levodo-
pa daily in four divided doses for three days.
The dosage was then increased by no more
than 250 mg every third day until the patient
showed beneficial results, or until he developed
side effects, or a total daily dose of 8 gm was
reached.
Prior to treatment, every patient had at least
two complete physical and neurological exami-
nations, and the following laboratory values
were obtained: white blood cell count, hemato-
crit, hemoglobin, urinalysis, blood glucose,
blood urea nitrogen, serum glutamic oxaloacetic
transaminase, Coombs' test, protein-bound io-
dine, and electrocardiogram. A complete physi-
cal and neurological examination and labora-
tory studies were repeated once a week for the
first month, then every 15 days in the second
month, and subsequently once a month. No
patient was lost to the follow-up even if the
drug was withdrawn. We have personally exam-
ined and followed up every patient reported.
The degree of disability of each patient is
classified according to the Columbia University
disability scale in five stages.10 Stage 1 indi-
cates unilateral involvement only. Stage 2 indi-
cates bilateral or midline involvement without
impairment of balance. Stage 3 signifies moder-
ate involvement with impairment of postural
and righting reflexes; however, the patient is
still able to lead an independent life. Stage 4
 194 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR

indicates fully developed severely disabling dis- On the contrary, patient 2 carried out whis-
ease, but the patient is still able to walk and pering conversations with an imaginary
stand. Stage 5 indicates confinement to bed or friend sitting at his side without any evi-
wheelchair unless aided.
Results
The psychiatric manifestations which oc-
curred in these 16 patients represent dis-
turbing side effects of levodopa and were
brought to our attention either by the dis-
tressed patients themselves or by members
of the family. They all represented intolera-
ble symptoms which required medical atten-
tion.
The data for each patient are found in
Table 1. The psychic disturbances vary con-
siderably in intensity and type. However,
they can be grouped into four major catego-
ries as shown in Table 1 and 2.
Psychotic Disorders.-Eight of the 45 pa-
tients or 17.7% developed a frank psychosis
with delusions, hallucinations, distortion of
reality, and various degrees of behavioral
disorder. During the psychotic episode, six
patients had an associated confusional state
with impairment of orientation, judgment,
and memory (group A of Table 1). The
remaining two subjects had an acute psy-
chosis with visual and auditory hallucina-
tions occurring in an otherwise clear senso-
rium (group B of Table 1). Patient 1, 4, and
5 of group A each had several episodes of
aggressive assaultive behavior during which
they appeared grossly confused and halluci-
natory. They were abusive, vociferous, and
attacked nurses, aides, and family members.
They all required physical restraint and se-
dation. Withdrawal of dopa was followed in
48 to 72 hours by disappearance of the
pvschosis in two of them (patient 1 and 4).
The third subject, 5, returned to his normal
prepsychotic state after the levodopa was
decreased from 2,750 to 2,500 mg and pyri-
doxine (12.5 mg daily) was added to the
regimen. At this reduced dose he was able to
maintain his motor improvement (from
stage 3 to stage 2) without any further
psychotic experience. The remaining three
patients of group A, No. 2, 3, and 6, had
frequent episodes of florid visual and audito-
ry hallucinations mostly of a persecutory
nature. Patient 2 and 3 appeared anxious,
restless, and frightened by their experience.
dence of concern. The psychosis cleared in
patient three 48 to 72 hours after withdraw-
al of the drug. Patient 2 was controlled by
diminution of medication. Patient 6 was
controlled by the addition of pyridoxine,
12.5 mg daily. In this case the levodopa dose
was left unchanged at 2,500 mg. This pa-
tient has been followed up for six months on
this regimen, and she has not experienced
any further difficulty.
It should be pointed out that five of these
six patients in group A had a mild chronic
organic brain syndrome manifested by for-
getfulness, impairment of cognitive func-
tions, and concrete thinking before the onset
of treatment. None of them had experienced
delusional thoughts or hallucinations before
the administration of levodopa with the ex-
ception of No. 4 who had occasional epi-
sodes of nocturnal hallucinations in the last
six months preceding this therapeutic trial.
Only No. 2 had normal mental functioning
at the beginning of therapy. However, she
had experienced an episode of toxic delirium
two years earlier while being treated with a
high dose of trihexyphenidyl hydrochloride
(Artane).
Levodopa was the only drug received by
four patients; two others, No. 5 and 6, were
kept on trihexyphenidyl hydrochloride, 10
mg and 6 mg daily, respectively, while re-
ceiving levodopa.
The two patients of group B who de-
veloped acute psychosis with clear con-
sciousness suffered from postencephalitic
parkinsonism. Patient 8 developed a psy-
chotic disturbance five months after the on-
set of treatment while receiving 1,875 mg of
levodopa daily. This dose had been reached
after a higher dose produced severe bucco-
lingual dyskinesia. She had been on this dose
for one month when she began experiencing
nocturnal hallucinations. Four to five days
later the hallucinations occurred also in the
daytime. They were stereotyped. She be-
lieved that three threatening men were
trying to attack her by breaking through the
windows. She also had severe constant buc-
colingual dyskinesia and dystonic move-
ments of neck and legs. The possibility of
anticholinergic toxicity was considered in

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 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR
this case because she was receiving procycli-
dine hydrochloride, 15 mg daily. The drug
was discontinued with no change in the
patient's behavior. Levodopa was then de-
creased to 1,500 mg and pyridoxine (12.5
mg daily) was started. Twelve hours later
her side effects had subsided. On this pro-
gram she has maintained the small motor
improvement, and her mental condition has
returned to normal. However, she still has
minimal intermittent buccolingual dyskine-
sia. Ten days after her mental status had
returned to normal, procyclidine was re-
sumed without reappearance of psychiatric
problems. Patient 7 has a past history of
obsessional preoccupation with body func-
tions. While receiving 2,500 mg daily of
levodopa she became worried about her
bowels, became restless and agitated, and
believed that she was having an intestinal
hemorrhage. She also had moderate bucco-
lingual dyskinesia and choreiform move-
ments of all four extremities. A week after
reduction of levodopa to 2,000 mg, her be-
havior had returned to normal and the dys-
kinesias are now tolerable. Since 1966 and
throughout the levodopa therapy trial, she
has been treated with benztropine mesylate,
6 mg daily.
An interesting feature of these eight cases
is the long latency between the onset of
treatment and the beginning of the psycho-
sis. The mean latency was four months. It is
important to note that usually the psychotic
disorder emerged after several weeks of
maintenance on a dose which had been ini-
tially well tolerated.
Another characteristic feature is the fre-
quent association of the psychic phenomena
with dyskinetic movements; this was seen in
six out of eight patients or 75% (Table 2
and 3). These movements may occur in the
form of buccolingual dyskinesia or as dys-
tonic and/or myoclonic involuntary contrac-
tions of neck, head, trunk, and limbs. The
most typical is the buccolingual dyskinesia
which consists of facial grimaces, tongue
protrusion and torsion, lip smacking and
licking, chewing movements, grinding of
teeth, and opening and closing of the mouth.
Euphoria.-Four patients became euphor-
ic during levodopa therapy. Their euphoric
or hypomanic state was characterized by
excessive self-confidence, over optimism,
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195
buoyancy, lack of inhibition, exaggerated
motor activity, and drive. They made inap-
propriate jokes, were garrulous, and were
often impudent.
Euphoria appeared to be related to dose
of levodopa and subsided when the dose
was reduced by 500 to 1,000 mg. In no case
was discontinuation of therapy necessary.
Euphoria was associated with dyskinesia in
all four cases. A typical example is patient
14 who developed euphoria and dyskinesia
after a month of levodopa treatment at a
dose of 4,500 mg. The euphoria subsided
four days after the drug was reduced to
3,500 mg daily. However, the buccolingual
dyskinesia was unchanged. When pyridox-
ine, 12.5 mg daily, was added, the dyskine-
sia became tolerable. Five months later,
while the patient was still treated with pyri-
doxine, levodopa was gradually increased to
5,250 mg without any euphoric effect. The
patient continued to have intermittent mild
mouth dyskinesia. Only one of these pa-
tients (No. 12) was concomitantly receiving
anticholinergic medication (trihexyphenidyl,
10 mg daily) with levodopa.
Acute anxiety.-Acute anxiety was char-
acterized by apprehension, nervousness, ir-
ritability, and a feeling of impending disas-
ter. Palpitations, hyperventilation, panting,
and insomnia were often associated with
anxiety. The intensity of the anxiety varied,
even in the same patient, from mild appre-
hension to severe panic.
As seen in Table 1, other psychic phenom-
ena sometimes occur either at the same or at
a different time in patients experiencing
anxiety. For instance, patient 10 developed
anxiety during a period of depression while
- receiving 3,500 mg of levodopa daily. She
would become apprehensive, restless, hyper-
kinetic, and ask for help and reassurance.
Such an episode would last four to five
hours, and then she would spontaneously
relapse into her prior taciturn depressed
state. A month prior to the onset of depres-
sion, this patient had an euphoric episode
while on dopa. For treatment of the depres-
sive symptoms, she was placed on an imip-
ramine hydrochloride regimen (75 mg dai-
ly). On this regimen she returned to normal
and has now remained free of psychiatric
problems for four months.
Three of the patients experiencing anxiety
 196 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR

Table 1.-Psychiatric Disturbances

Duration of
Disease Treatment
Stage Anticho- Before Psychosis
Dura- -----linergic Onset of Levodopa
No. Parkinson tion Ini- Pres- Thala- Medi- Disturbances Dose Group Group
Patient Type Sex Age (yr) tial ent motomy cations (Mo) (mg) A B
1 Primary M 74 20 5 3 - - 8 4,000 + -

2 Primary F 56 10 3 2 B - 1 4,000 + -

3 Primary F 58 7 4 3 - - 2 2,500 + -

4 Primary M 68 15 5 5 - - 5 4,000 + -

5 Primary M 69 17 3 2 L + 5 2,750 + -

6 Arterio- M 72 10 5 4 - + 2 3,500 + -

sclerotic
7 Postenceph- F 66 37 5 4 B + 3 2,750 - +
alitic
8 Postenceph- F 61 35 4 3 - + 5 1,875 - +
alitic
9 Primary F 74 14 4 3 B + 2 5,000 - -

10 Primary F 61 10 4 3 - - (3) 4t 3,500 - -

11 Primary F 71 4 3 3 - + 3 2,500 - -

12 Postenceph- M 66 49 4 3 - + 2 3,250 - -

alitic
13 Primary M 25 12 3 0 - - 2 5,000 - -

14 Primary M 67 8 3 2 - - 1 4,500 - -

15 Primary F 62 11 3 3 B - 4 7,000 -

16 Primary M 72 9 4 3 - - 1 4,000 -

* B indicates bilateral; L, left; +, present; -, not present; W, withdrawal; P, pyridoxine; D, diminution; AD, anti-
depressant; A, abnormal; N. normal.

Table 2.-Incidence of Psychiatric Disburbances in 45 Patients Receiving Levodopa

Worsening of
Psychotic Acute Basal Mental
Disorders Euphoria Anxiety Depression Status
No. of patients* 8 4 4 2 5
% of patients 17.7 8.8 8.8 4.4 11.1
No. of patients with
dyskinesia 6 4 4 2 4
No. of patients with
pretreatment mild
dementia 5 0 0 0 4
Mean dose of
levodopa (mg) 3,172 4,062 3,562 5,250 3,900
Mean duration of therapy
before onset of
symptoms (mo) 4 2 3 4 4
* Some patients had more than one type of psychiatric manifestation.

responded either to a diminution of levodo- to her pretreatment status. Three of these

pa or to the use of a psychotropic drug. The
only exception was patient 11 who refused
to continue levodopa therapy because of in-
tolerable anxiety and restlessness. One week
after she stopped levodopa, she had returned
patients were receiving trihexyphenidyl to-
gether with levodopa. In the past they had
never experienced anxiety while taking anti-
cholinergic medication alone.
Other Psychiatric Disturbances.-Two oth-

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 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR 197

of Levodopa Therapy*
Past
History of
Dyskinesia Control of Duration Pretreat- Psychiatric
Worsen- Psychic of ment Disorders
ing Basal Bucco- Disturbances Treatment Mental Other Than
Euphoria Anxiety Depression Status lingual General Achieved by (mo) Status Dementia
- - - + + - W 8 A -
54- - - - - - W 1 N Reactive
depression
- - - + + - P 8 A -
_ _ - + - - W 5 A -
- - - - + + D+P 6 A -
- - - - + - D 2 A -

- - - - + + D 4 N Neurosis

7- - - - + + D+P 6 N -
- + - + + - D 3 N Neurosis
+ + + - + - AD 8 N Reactive
depression
- + - - + + W 3 N -
+ + - - + + D 6 N -

+ - - - - + D 6 N -
+ - - - + + D+P 10 N -
- - + - + - AD 9 N Reactive
depression
- - - + + - D 3 A -
t (3) refers to duration of treatment in months before onset of euphoria, while 4 refers to duration of treatment
before onset of depression.

Table 3.-Association of Psychic Phenomena With Dyskinetic Movements

Psychiatric Disturbances Dyskinesia Levodopa Dose (mg)
No. of . ^- . . . Pretreatment
Patients No. % No. % Dementia Mean Range
Total patients 45 16 35.5 28 62.2 7 4,319 1,875-8,000
receiving levodopa
Patients with 16 16 100 14 87.5 6 3,757 1,875-7,000
psychiatric
disturbances

er psychiatric manifestations were ob- Worsening of the baseline mental status

served during levodopa therapy: depression
and worsening of already impaired mental
function. Two women who in the past had
suffered from reactive depression became se-
verely depressed while taking levodopa.
Their depression occurred either after a set-
back in improvement or after the patient
realized that the therapy was not as effective
as had been anticipated. Both patients re-
sponded to imipramine. In both cases levo-
dopa was the only drug used at the time. In
patient 10 trihexyphenidyl was later added
to the dopa without reappearance of psychi-
atric difficulties.
was observed in five subjects. In one case
(No. 9) a worsening of the already existing
neurosis was noted. The remaining four pa-
tients had a mild chronic organic brain syn-
drome; while receiving dopa they developed
increasing confusion, increasing memory
deficit, and were disoriented at times. Three
of these individuals developed episodes of
psychosis as reported above. The only pa-
tient receiving anticholinergic drugs was pa-
tient 9.
Comment
Side effects from levodopa are frequent,

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 198 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR
but its benefits far outweigh its shortcom-
ings. We have chosen to focus our attention
on the mental disturbances encountered dur-
ing levodopa therapy because together with
the dyskinesia they have represented the
major limiting factor in this therapy. Psy-
chiatric disturbances including restlessness,
hypersexuality, depression, euphoria, confu-
sion, and toxic delirium have been reported
by several authors2-6""',12 (Table 4).
In our series psychiatric phenomena oc-
curred in 35.5% of the patients. Psychic side
effects have been reversible in all our cases
as well as in all those reported in the litera-
ture. The disappearance of the symptoms
was achieved in 12 subjects by readjustment
of the dose or the use of an antidepressant;
only in four of our cases was withdrawal of
dopa necessary. In nine cases levodopa was
the only medication being administered at
the time of the appearance of psychiatric
disturbances. Seven patients were simultane-
ously receiving an anticholinergic drug. With
regard to these latter cases, the possibility
that anticholinergic agents either contributed
to or produced the psychiatric phenomena
must be considered. However, these reactions
did not occur until levodopa was added to
the therapeutic regimen. These patients had
received the same amount and type of anti-
cholinergic drugs for six months to seven
years (mean 31 months) before the onset of
mental disturbances. Furthermore, in subject
8, the psychotic reaction did not disappear
when procyclidine alone was discontinued.
It was only after the reduction of levodopa
that her mental status returned to normal.
Later, on a lower dose of levodopa, procycli-
dine was reintroduced with no difficulty. In
every patient the diminution or withdrawal
of levodopa was sufficient to restore normal
mental functioning. Subjects 10 and 14 de-
veloped behavioral changes while receiving
levodopa alone; their difficulty was controlled
by adjustment of levodopa. At a later date
both were started on a trihexyphenidyl regi-
men without reappearance of psychiatric
phenomena.
These data are against the role of anti-
cholinergic drugs as the sole cause of behav-
ioral changes; they strongly suggest that
levodopa is responsible for these reactions.
However, in some cases we cannot exclude
the possibility that anticholinergic agents
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may have contributed to the psychiatric dis-
turbances.
Patients with Parkinson's disease and as-
sociated chronic organic brain syndrome
and patients with postencephalitic parkin-
sonism appeared prone to develop acute
psychosis. Seven of the 45 patients in our
study had a mild dementia, and only one of
these seven escaped mental complications
during levodopa therapy: five became psy-
chotic, and one had a worsening of his de-
mentia. Each of the three subjects with post-
encephalitic parkinsonism experienced psy-
chiatric symptoms, and two of them became
psychotic. The postencephalitic patients also
showed a lower tolerance to the drug, de-
veloping side effects at a lower dose than
patients with Parkinson's disease (Table 1).
This is in agreement with the experience of
Calne et al4 who reported psychiatric dis-
turbances in 55.5% of their patients receiv-
ing levodopa for the management of post-
encephalitic parkinsonism. These results
should not be interpreted as advocating the
exclusion of patients with mild dementia or
postencephalitic parkinsonism from levodo-
pa therapy. However, such patients should
be treated cautiously. These adverse reac-
tions are dose related and therefore can be
prevented by careful monitoring of the pa-
tients, preferably on an inpatient basis. The
occurrence of minor changes in the mental
status or dyskinetic movements indicates the
necessity for decreasing or even stopping the
levodopa.
An interesting feature of our findings is
the association of involuntary dyskinetic
movements and psychic disturbances. The
agitated confused patient with vivid visual
and auditory hallucinations and buccolin-
gual or generalized dyskinesia presents a
unique clinical picture characteristic of levo-
dopa toxicity. As far as we are aware, no
other drug has ever been reported to pro-
duce this psychosis-dyskinesia complex. The
levodopa psychosis-dyskinesia complex pre-
sents some fascinating similarities to other
clinical entities such as Huntington's chorea,
Wilson's disease, chronic manganese poison-
ing, and tardive dyskinesia secondary to
phenothiazines.13 It also suggests the possi-
bility of a role for basal ganglia and cate-
cholamines in behavior.
Catecholamines and other brain mono-
 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR 199
Table 4.-Incidence of Psychiatric Disturbances in Patients
Receiving Levodopa for the Treatment of Parkinsonism
Psychiatric Disturbances
No. of
Author Patients Treated No. %
Barbeaull 80 22 27.5
Caine et als 26 4 15.4
Caine et al4 20 11 55.5
Cotzias et alZ 28 1 3.5
Godwin-Austen et alz2 18 5 27.7
McDowell et al' 100 14 14.0
Yahr et al3 60 10 16.6
Celesia and Barr 45 16 35.5

amines have been implicated in the etiology
of psychotic disorders.7-9 Psychotic symptoms
have also been induced in rats and mice by
the intravenous administration of dopa.14,15
Levodopa administration in animals pro-
duces an increase in the content of brain
norepinephrine.16-18 Reis et al'8 found that
levodopa induces excitement and sham rage
in cats pretreated with monoamine oxidase
inhibitors. Furthermore, they demonstrated
that this reponse is due to norepinephrine.
The antipsychotic effects of reserpine and
phenothiazine have also been related to
their antagonism of norepinephrine.8,9 How-
ever, other biogenic amines are also affected
by these drugs.15
Dopamine itself may also be directly in-
volved in the generation of abnormal behav-
ior. Ernst'9 has produced bizarre behavior
and a syndrome of gnaw-compulsion in rats
by direct implantation of dopamine into the
dorsal part of the caudate nucleus or into
the globus pallidus. It is ineffective when
placed in the ventral part of the caudate,
subthalamic structures, or substantia nigra.
The importance of the caudate nucleus in
behavior and mental function is also sug-
gested by the results of direct stimulation.
Van Buren2O stimulated the head of the
caudate nucleus in man and produced amne-
sia for the period of stimulation, disturbance
of speech, euphoria with smiling, laughter or
brightening of mood, and a loss of respon-
siveness to visual or auditory cues during
stimulation. This response was not obtained
when other basal ganglia or surrounding
structures were stimulated.
While indicating a close interaction
among basal ganglia, biogenic amines, motor
and mental functions, these data do not
suggest a theory invoking a single biochemi-
cal defect. They suggest, rather, a more
complex situation and the existence of a
delicate balance among different biogenic
amines. Disruption of this equilibrium may
lead to a pathological condition which varies
with the direction of the interference. Bert-
ler and Rosengren2' have shown in hog
brain extracts a competitive inhibition be-
tween dopa and 5-hydroxytryptophan. They
also observed that in rabbits injections of
levodopa lowered the brain 5-hydroxytrypta-
mine level to 50% to 60% of normal. The
possibility that an excess of levodopa or
dopamine may displace other amines from
their normal storage sites or interfere with
their metabolism has been proposed by Yahr
et al.3 The undesirable reactions to levodopa
may then be interpreted as a combination of
increased dopamine and dysfunction of the
metabolism of norepinephrine, serotonin,
and other amines.
The occurrence of depression in patients
undergoing levodopa therapy",22 is only ap-
parently contradictory to the concept of
norepinephrine deficiency in depression. Levo-
dopa increases the tissue content of dopa-
mine and to a lesser extent of norepineph-
rine,16-'8 but it may not raise depressed
norepinephrine levels up to normal. The
efficacy of imipramine can be explained by
a selective increase of norepinephrine to
restore the monoamine balance.23 An interest-
ing finding has been the pyridoxine antago-
nism of levodopa reported initially by Duvoi-
sin et a124 and later confirmed by Cotzias.25

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 200 LEVODOPA PSYCHOSIS-DYSKINESIA-CELESIA & BARR
No satisfactory explanation is yet available
for this antilevodopa effect of pyridoxine.
We have found that small doses of pyridox-
ine, between 12.5 to 24 mg, sometimes help
to counteract the adverse reaction of levodo-
pa while not interfering with the overall
improvement obtained from it.
Summary
Levodopa is an effective drug for the
treatment of parkinsonism. However, mental
disturbances occur not infrequently during
its administration. Sixteen of 45 patients
receiving levodopa developed psychiatric
phenomena. Psychosis, acute anxiety, eu-
phoria, and other psychic phenomena are
described in detail. Fourteen of the 16 pa-
tients, or 87.5%, had associated buccolin-
gual or generalized dyskinesia. This associa-
tion of psychic disorder with buccolingual or
generalized dyskinesia is characteristic of
levodopa toxicity. The levodopa psychosis-
dyskinesia complex is reversible and most
frequently controlled by diminution of levo-
dopa dose. It occurs mostly in patients with
associated organic brain syndrome or those
suffering from postencephalitic parkinson-
ism. The interesting relationship between
psychiatric manifestations, dyskinesia, basal
ganglia, and biogenic amines is discussed.
Levodopa was supplied as Larodopa by Hoffmann-
LaRoche, Inc.
Nonproprietary and
Trade Names of Drugs
Dopamine hydrochloride-Intropin.
Procyclidine hydrochloride-Kemadrin.
Levodopa-Larodopa.
References
1. Cotzias GC, Van Woert MH, Schiffer LM:
Aromatic amino acids and modification of parkin-
sonism. New Eng J Med 276:374-379, 1967.
2. Cotzias GC, Papavasiliou PS, Gellene R:
Modification of parkinsonism: Chronic treatment
with L-Dopa. New Eng J Med 280:337-345, 1969.
3. Yahr MD, et al: Treatment of parkinsonism
with levodopa. Arch Neurol 21:343-354, 1969.
4. Calne DB, et al: L-dopa in postencephalitic
parkinsonism. Lancet 1:744-746,1969.
5. Calne DB, et al: L-Dopa in idiopathic parkin-
sonism. Lancet 2:973-976, 1969.
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