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Synonyms, Key Words, and Related Terms: buccolingual, orofacial dyskinesia, masticatory dyskinesia
James Robert Brasic, MD, Brian Bronson, MD, Daniel H Jacobs, MD, Francisco
Talavera, PharmD, PhD, Nestor Galvez-Jimenez, MD, Selim R Benbadis, MD,
Nicholas Lorenzo, MD
Background: Tardive dyskinesias (TDs) are involuntary movements of the tongue, lips,
face, trunk, and extremities that occur in patients treated with long-term dopaminergic
antagonist medications. Although associated with the use of neuroleptics, TDs apparently
existed before the development of neuroleptics. People with schizophrenia appear
especially vulnerable to developing TDs after exposure to neuroleptics, toxins, and other
agents. TDs are seen most commonly in patients with schizophrenia, schizoaffective
disorder, or bipolar disorder who are treated with antipsychotic medication, but they
occasionally are seen in other patients as well.
TDs may be differentiated from acute movement disorders that occur commonly in the
same patient groups. The acute movement disorders that occur as manifestations of
effects of neuroleptics and other dopamine antagonists include akathisia, acute dystonia,
and other hyperkinetic dyskinesias. Acute effects of dopamine antagonists also include
parkinsonian syndromes manifested by bradykinesia, rigidity, and pill rolling tremor. The
acute movement disorders resulting from exposure to dopamine antagonists commonly
are termed extrapyramidal syndromes (EPS).
Extrapyramidal dysfunction
Dopamine system
While the dopamine D2 receptor traditionally has been implicated in the pathogenesis of
TD, mounting evidence exists that for some individuals, the dopamine D3, D4, and D5
receptors are involved.
Clinical presentation
Patients often exhibit movement disorders that actually may represent a mixture or
overlap of several dyskinesia disorders. Individuals treated with neuroleptics may
demonstrate both acute and chronic effects, manifested by acute dyskinesias and TD.
Individuals simultaneously may manifest akathisia and tics after long-term treatment with
neuroleptics.
The diagnosis of acute and chronic dyskinesias may be difficult without a past history
when seeing a patient for the first time. Precise documentation of a patient's complete
movement history and medication history may facilitate accurate delineation of
movement disorders. Thus, a full neurologic and pharmacologic history may provide the
basis to distinguish idiopathic Tourette disorder from acute medication-induced tardive
tics.
Often patients and families cannot provide accurate histories, thus firm diagnoses may be
impossible. Since acute and tardive medication effects can be observed simultaneously,
the distinction may be challenging in a clinical setting. Observing patients carefully on a
regular basis with precise documentation at each visit, through structured rating
instruments, of the phenomenology and topography of movements and the pharmacologic
treatments helps to provide a basis for accurate future diagnosis of acute and tardive
dyskinesias.
Frequency:
Orofacial TDs differ from peripheral TDs in the occurrence of comorbid acute
movement disorders. Acute tremor, acute akathisia, and acute parkinsonism are
more common in people with peripheral TD. Distinguishing acute and tardive
dyskinesias in an individual patient can represent a serious diagnostic challenge.
Sex: Elderly female patients appear to be particularly susceptible. Young men are prone
to develop tardive blepharospasm and tardive dystonia.
Age: Advanced age is a major risk factor for TD. Prevalence in elderly patients treated
with dopamine antagonists is reportedly 29% after 3-12 months of treatment and 41%
after 10 years of treatment.
CLINICAL
History:
Physical:
The neuroleptic-induced orofacial form constitutes the prototype of TD. This type
is characterized by irregular movements of variable amplitude and low frequency.
The individual initially may be unaware of the movements. Family and friends
may draw attention to the movements. Puckering, smacking, opening, and closing
of the lips may occur constantly. The person may appear to be chewing or sucking
on items. The movements resemble those of people with ill-fitting dentures.
Inquire about the use of dentures. Inquire if the person is aware of movements in
the mouth, face, hands, and feet. Ask if dentures or teeth bother the patient. The
tongue may protrude briefly out of the lips. If asked to maintain a protruded
tongue, the person may be unable to keep the tongue out more than a second.
While the individual may attempt to disguise the movements by placing the hand
to the mouth, in time, the movements become constant during waking hours and
cannot be suppressed by the patient.
TD is expressed in the tongue, cheeks, mandible, perioral area, and other regions
of the face, fingers, and toes. Various facial movements (eg, lip smacking,
chewing, sucking, puckering, tongue writhing, tongue protrusion, jaw opening,
jaw closing, grimacing) are observed. TD may be observed in the upper face with
excessive blinking and brow wrinkling.
Guitar and piano playing movements and other flexion and extension movements
of the fingers and/or wrists can be observed. Flexion and extension movements of
the ankles and toes are characteristic. Dyskinetic movements of the neck, trunk,
and pelvis occasionally can occur. Jerking movements of the abdomen and
diaphragm resulting in respiratory irregularity may occur.
Tardive tics may be observed in affected patients. Since the patient may suppress
the tics temporarily, they may not be observed during the initial encounter.
Tardive tremor manifests as involuntary rhythmic sinusoidal movements of limbs,
head, neck, or voice. Tardive tremors are persistent. Unlike cerebellar tremors,
which are present on voluntary motion and not at rest, and psychogenic tremors,
which diminish during the course of long examinations, tardive tremors usually
are present at rest and with voluntary movement.
The presence of stereotypies can be assessed readily using the Timed Stereotypies
Rating Scale (see Figure 9).
o For this assessment, observe the subject with bare feet and exposed hands.
Ask the subject to sit still in a chair for 10 minutes. Place a check mark on
the score sheet (see Figure 9) the first time that each movement occurs
during each 30-second interval of the 10-minute observation period. This
can be accomplished by playing an audiotape dictating 30-second intervals
of a 10-minute duration (Download Audio Segment) The tape may be
played live in the presence of the subject. To avoid distracting the subject,
the examiner may listen to the audiotape through headphones.
o Another option is to videotape the subject for at least 10 minutes and then
to rate the videotape with the audiotaped dictation of 30-second segments
of a 10-minute duration later. Optimally, the subject is rated both live and
on videotape. The videotape is rated by examiners blind to the status of the
subject. Test-retest reliability thus can be determined by assessing the
ratings of the live and videotape sessions.
o Often videotapes miss crucial events, such as a tear or a jerk. In the blank
spaces in items 23-50 at the end of the form, add additional movements of
the subject (eg, toe wiggling, rubbing feet on floor, extending arms at
elbow, extending legs at knee, patting feet on floor). Also, on the blank
space at the end of the form add additional utterances of the subject (eg,
grunts, snorts, throat clearing, vowels, syllables, words, sentences). The
sessions may be videotaped. Using a toggle switch on a videocassette
recorder, the videotapes may be played back frame by frame to facilitate
the observation of each occurrence of every stereotypy.
Causes:
Long-term treatment with dopamine antagonists can cause TD. It also can be
caused by both high-potency and low-potency traditional neuroleptics, including
long-acting depot formulations (eg, decanoate). Newer atypical antipsychotic
agents, including clozapine and risperidone, appear to carry less risk of TD.
TDs also have been reported with the use of antihistamines, fluoxetine,
amoxapine (a tricyclic antidepressant), and other agents (see Figure 2).
Psychogenic movement disorders often are florid and bizarre.
DIFFERENTIALS
WORKUP
Lab Studies:
Imaging Studies:
Computed tomography (CT) scan and MRI of the brain typically are normal in
TD. However, these imaging studies may assist in differential diagnosis.
Other Tests:
Procedures:
TREATMENT
Medical Care:
Primary prevention of TD by using the lowest effective dose of neuroleptic for the
shortest period of time is recommended. Upon diagnosing TD, reduce or
discontinue the causative agent if possible. The risk of a permanent movement
disorder must be weighed against the risks of exacerbating psychosis. In addition,
TD initially may worsen after discontinuing neuroleptics.
Atypical neuroleptics may control psychosis while reducing the risk of TD. While
traditional neuroleptics primarily block D2 dopamine receptors, atypical
neuroleptics bind variably to dopaminergic, serotonergic, alpha-adrenergic,
histaminic, and muscarinic receptors. In particular, clozapine has been
recommended as treatment for patients with TD who require antipsychotics.
Clozapine is one of the most effective atypical neuroleptics in treatment-
refractory schizophrenia. While clozapine has been associated with TD, the
incidence of TD with this and other atypical agents appears markedly less than
with traditional neuroleptics. The beneficial effects of clozapine probably result
from its affinity for the dopamine D4 receptor. However, risperidone and
clozapine may be ineffective in treating negative and positive symptoms in some
patients. Also, treatment with clozapine requires regular hematologic evaluation
to avoid fatal agranulocytosis.
For tardive tics, remove the causative neuroleptic if possible. If the patient cannot
tolerate absence of the neuroleptic, substitute an atypical neuroleptic. Pimozide,
clonidine, and haloperidol can be helpful in some patients with tardive tics.
Clozapine has treated tardive tremor successfully. Propanolol is useful for tardive
akathisia. Clonazepam has been reported to successfully alleviate the symptoms
of tardive dyskinesia as well as spontaneous oral dyskinesia.
Consultations:
o Psychogenic movement disorders are some of the most bizarre and florid
movement disorders. Typically, psychogenic movement disorders do not
demonstrate the usual phenomenology and topology of TD.
o Patients may have both psychogenic movement disorders and TD. The
primary clinician tactfully and diplomatically must suggest to the patient
that consultation to investigate psychological aspects may be helpful.
MEDICATION
Reduction and cessation of the causative agents may relieve tardive symptoms. Anecdotal
reports have suggested that various agents have helped individuals. No established
medications exist to treat TD.
MISCELLANEOUS
Medical/Legal Pitfalls:
Before administering any treatment that may block dopamine receptors, obtain
informed written consent. Additionally, all patients currently treated with
dopamine antagonists, even those with schizophrenia treated with traditional
neuroleptics for many years, merit re-evaluation for possible change of
medication. Atypical antipsychotics, such as risperidone and clozapine, appear to
have a lower risk of TD. Obtain written informed consent to acknowledge the risk
of possible TD from patients treated with dopamine antagonists for any diagnosis
including migraine, hiccups, and gastroesophageal reflux. Throughout the course
of therapy, reevaluate the need for continuation of neuroleptics (see Table 1).
Patients with TD who require continued treatment with a neuroleptic may benefit
from atypical neuroleptics.
Fully inform the patient (or the legal surrogate if the patient is incompetent) of the
possible courses of action. Discuss with the patient the advantages and
disadvantages of dopamine antagonist treatment. A written treatment plan that
documents agreement with the treatment course between the clinician and patient
is helpful. Regularly review and revise the treatment plan as needed.
Special Concerns:
o Before and during treatment, assess the need for treatment with
psychoactive medication (see Figure 4).
FIGURES
Butyrophenones
o Droperidol (Inapsine)
o Haloperidol (Haldol)
Dibenzodiazepines
o Loxapine (Daxolin, Loxitane)
Diphenylbutylpiperidines
o Pimozide (Orap)
Indolones
o Molindone (Moban)
Phenothiazines
o Chlorpromazine (Thorazine)
o Fluphenazine (Permitil, Prolixin)
o Mesoridazine (Serentil)
o Perphenazine (Trilofan)
o Thioridazine (Mellaril)
o Trifluoperazine (Stelazine)
Thioxanthenes
o Thiothixene (Navane)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Oral contraceptives
o Estrogens
Stimulants
o Amphetamine (Adderall)
2. Ask patient if there is anything in his/her mouth (eg, gum, candy); if there is, to
remove it.
3. Ask patient about the current condition of his/her teeth. Ask patient if he/she
wears dentures. Do teeth or dentures bother the patient now?
4. Ask patient whether he/she notices any movements in mouth, face, hands or
feet. If yes, ask to describe and to what extent they currently bother patient or
interfere with his/her activities.
5. Have patient sit in chair with hands on knees, legs slightly apart and feet flat on
floor. (Look at entire body for movements while in this position.)
6. Ask patient to sit with hands hanging unsupported. If male, between legs, if
female and wearing a dress, hanging over knees. (Observe hands and other body
areas.)
7. Ask patient to open mouth. (Observe tongue at rest in mouth.) Do this twice.
8. Ask patient to protrude tongue. (Observe abnormalities of tongue movement.)
Do this twice.
9. Ask patient to tap thumb, with each finger, as rapidly as possible for 10 to 15
seconds; separately with right hand, then with left hand. (Observe facial and leg
movements.)
10. Flex and extend patient's left and right arms (one at a time). (Note any
rigidity.)
11. Ask patient to stand up. (Observe in profile. Observe all body areas again, hips
included.)
12. Ask patient to extend both arms outstretched in front with palms down.
(Observe trunk, legs and mouth.)
13. Have patient walk a few paces, turn and walk back to chair. (Observe hands
and gait.) Do this twice.
B) Rating Sheet
01234
8. Severity of Abnormal Movements
Global
9. Incapacitation Due to Abnormal Movements 01234
Judgments
10. Patient's Awareness of Abnormal Movements
01234
Rate only patient's report.
INSTRUCTIONS TO RATER:
CAREGIVERS
23. Primary clinician
24. Physician 1 managed medications for person
25. Physician 2 managed medications for person
26. Physician 3 managed medications for person
PAST HISTORY
TARGET SYMPTOMS
82. Significant symptom observed by more than one
Y
staff member.*
83. There is an obvious environmental cause for the
Y
symptom.+
84. There is an obvious bias by the observer; others
Y
do not agree.+
85. More than one significant symptom is observed. Y
86. A hierarchy of symptom priorities for treatment is
Y
listed.*
87. Target symptom(s) for treatment established.* Y
88. Baseline ratings of symptoms obtained by rating
Y
scales.
89. Baseline ratings of symptoms obtained by
Y
informal observation.*
90. Other target behavioral symptoms are identified.
If yes, please list:
Y
TREATMENT SELECTION
92. Only one available psychoactive treatment is
Y
considered and reviewed.+
93. More than one available psychoactive treatment is
Y
considered and reviewed.*
94. Beneficial and side effects of each psychoactive
Y
treatment are reviewed.*
95. Sequence of psychoactive treatments is
Y
established.*
96. Caution to do no harm to person in treatment
Y
selection.*
97. Informed consent is obtained prior to starting
Y
psychoactive medication.*
98. Class of psychoactive medication selected in
Y
relation to psychiatric diagnoses.*
99. Class of psychoactive medication selected in
Y
relation to target behavioral symptom(s).*
100. Class of psychoactive medication selected in
Y
relation to concurrent medical illnesses.*
101. Class of psychoactive medication selected in
Y
relation to drug interactions.*
102. Psychoactive medication(s) excluded because
Y
contraindicated or ineffective.
103. Psychoactive medication(s) retained as Y
alternative.*
DRUG HOLIDAYS
136. Drug holiday of at least four weeks each year Y
planned.
137. Drug holiday of at least four weeks this year
Y
attempted.
138. Drug holiday of at least four weeks this year
Y
completed.
139. No drug holiday, with documentation supporting
Y
this decision.
140. Attempt at drug holiday was discontinued, with
Y
justification.
Name
Rater
Date
0 = Absent
1 = Questionable
2 = Present and easily controlled
3 = Present and barely controlled
4 = Present and not controllable
S
S
t
i L T
a
t y o
n
t i t
d
i n a
i
n g l
n
g
g
SUBJECTIVE ITEMS:
d
1. Patient has sensation of inner restlessness: ____ ____ ____ ____
2. Patient has the urge to move: ____ ____ ____ ____
d
OBJECTIVE ITEMS:
d
3. Akathisia present in the head and trunk: ____ ____ ____ ____
4. Akathisia present in the hands and arms: ____ ____ ____ ____
5. Akathisia present in the feet and legs: ____ ____ ____ ____
0 = No akathisia
1 = Questionable
2 = Small amplitude movements, part of the time
3 = Small amplitude movements, all of the time OR large amplitude movements, part of
the time
Considering your total clinical experience with this particular population, how akathisic
is the patient at this time?
0 = Not assessed
1 = Normal, not akathisic
2 = Borderline akathisia
3 = Mildly akathisic
4 = Moderately akathisic
5 = Markedly akathisic
6 = Severely akathisic
7 = Among the most akathisic of patients
SCORE
Global Improvement:
____
Rate total improvement whether or not, in your judgment, it is entirely due to drug
treatment.
Compared to his/her condition at admission to the study, how much has he/she changed?
0 = Not assessed
1 = Very much improved
2 = Much improved
3 = Minimally improved
4 = No change
5 = Minimally worse
6 = Much worse
7 = Very much worse
Reproduced from Fleischhacker, Bergmann, Perovich, et al.
Fill out separate checklists for each different movement, posture, or utterance
observed. Do not rate two or more particular movements, postures, or utterances
on the same sheet. Please complete the following items based on all available
sources of information concerning each movement, posture, or utterance on the
rating date.
Name:
Rater:
Date:
Define the indicator functions, Yi and i, 1 < i < 23, to correspond to the items {Xi,
1 <= i <= 23} of the Movement Disorders Checklist (Figure
7) according to the following procedure:
Let
Similarly, let
Then, define the additional indicator functions, Zj, 1 <= j <= 4, as follows:
1 if X14 = 1 or X17 = 1 (3)
Z1 (Xj) =
{ 0 otherwise
1 if X7 = 1 or X23 = 1 (4)
Z2 (Xj) =
{ 0 otherwise
Let
A 2 = A 1 + Z2 (10)
A3 = Y2 + Y3 + Y5 + Y9 + 15 (11)
Then chorea is present if Y2 = Y3 = Y5 = Y9 = 15 = 1, or, equivalently, if A3
= 5 by Equation (11).
A 6 = 5 + Y2 + Y3 + Y4 + Y8 (14)
Then tic is present if 5 = Y2 = Y3 = Y4 = Y8 = 1, or, equivalently, if A6 = 5
by Equation (14).
A7 = Y10 + Z4 (15)
Although this rating scale can be used with a stopwatch, it is best used with a recording
of a 30-second interval timing (up to 10 min), which is available in MP3 format.
(Windows Media Player supports this format; MAC users can download an MP3 player
here.) Please download this MP3 audio file and dub it to a recording device (eg, tape
recorder) via the computer's audio output jack to create a copy to use when administering
the timed stereotypies rating scale.
Rater:
Name:
Date:
Time:
Place:
0:00 0:30 1:00 1:30 2:00 2:30 3:00 3:30 4:00 4:30 5:00
1.
Eyebrows
2. Mouth
Twitching
3.
Grimacing
4. Forceful
Breathing
5. Smelling,
Sniffing
6. Bronx
Cheer
7. Biting
8. Chewing
(including
tongue,
cheek)
9. Mouth
Opening
10. Teeth
Grinding
11. Tongue
in & out
12. Tongue,
Sustained
Protruding
13. Hand
Flapping
14. Finger
Wiggling
15.
Slapping
(objects)
16.
Covering
Ears
17.
Covering
Eyes
18.
Spinning
Objects
19. Tip-toe
Walking
20. Body
Rocking
21. Head
Rolling
22. Head
Tilting
23. Other
24. Other
25. Other
26. Other
27. Other
28. Other
29. Other
30. Other
31. Other
32. Other
33. Other
34. Other
35.
Oth
er
36.
Oth
er
37.
Oth
er
38.
Oth
er
39.
Oth
er
40.
Oth
er
41.
Oth
er
42.
Oth
er
43.
Oth
er
44.
Oth
er
45.
Oth
er
46.
Oth
er
47.
Oth
er
48.
Oth
er
49.
Oth
er
50.
Oth
er
PICTURES
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