Psychiatric medications, especially antipsychotics and antiemetics, are commonly implicated in causing movement disorders by affecting dopamine receptors in the brain. Movement disorders induced by medications can include parkinsonism, dystonia, akathisia, tardive dyskinesia, chorea, myoclonus, tics, and neuroleptic malignant syndrome. The time of onset, severity, and treatment depend on the specific disorder, but eliminating the offending medication is usually the first approach except for tardive phenomena which may persist. Careful evaluation of medication history and neurological examination are important for diagnosis.

1. Movement Disorders Induced by
Psychiatric Medications
Ahmad Shahir Mawardi
Neurologist,
Neurology Department
Hospital Kuala Lumpur
25th November 2020

2. 2
Introduction
Antipsychotics and antiemetics are most commonly implicated
drugs can cause movement disorders (MD)
The time of onset of the movement disorder may be acute,
subacute, or chronic.
may be focal, hemi-, or generalized in nature.
The severity can range from mild to severe and life-
threatening.

3. 3
Introduction
e. g parkinsonism, tardive phenomena, chorea, dystonia,
tremor, akathisia, myoclonus, tics, and neuroleptic malignant
syndrome
The drug-induced MDs, usually treated by elimination of the
offending medication exception of the tardive phenomenon
Challenge: some of the motor signs may be misinterpreted as
psychotic symptoms.

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Movement disorders
• condition that includes involuntary movement that
are abnormal in initiation, implementation, velocity,
frequency or posture.

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Broadly . . .
Hyperkinetic Movements
Hypokinetic Movements

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• Tremor
• Tics/Tourette syndrome
• Dystonia
• Hemifacial spasm
• Ataxia
• Chorea/Balism/Athetosis
• Myoclonus
• Others
 Myokymia
 Myorhythmia
 Restless Legs
 Hyperekplekia
 Akathisia
• Parkinsonism
 Catatonia
 Psychomotor depression
 freezing Phenomenon
 Hypothyroid slowness
 Stiff muscle
Hyperkinetic
Movements
Hypokinetic
Movements

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The spectrum of hyperkinetic MD

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• sometimes a few
may coexist!
• For example,
Ballismus, Chorea,
Athetosis and
Dystonia often co-
exist.
The spectrum of hyperkinetic MD

9. Outline of today’s lecture
Clinical Scenario
Pathophysiology
Classification
Common MD caused by anti-psychotic
Approach
Treatment
Conclusion

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Clinical scenario
• A 42-year-old male presents with the complaint of hand shaking for the past 6
months, which is causing him some social disability. He denies any interference
with eating or ADL.
• He has a past history significant for bipolar disorder with psychotic features. He
has been treated for years with carbemazepine for mood stabilization and
within the past year was started on risperidone for psychotic features.
• On neurologic examination, the patient has a resting tremor of both upper
extremities, bradykinesia of rapid alternating movements in the upper and
lower extremities, and cogwheel rigidity of all extremities. With gait testing, he
has a diminished arm swing and mild retropulsion with the pull test.
• He is diagnosed with drug-induced parkinsonism, and risperidone is eliminated
by his psychiatrist.
• Two months later the patient no longer has any tremor, bradykinesia, rigidity, or
gait abnormalities. He currently has some paranoid ideations that will require
treatment.

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Pathophysiology
• Unclear, but certain theories and hypothesis suggest
the interplay between:
– genetic predisposition,
– dopaminergic system hypersensitivity in the BG
– decreased functional reserve
– over activation of the cholinergic system.

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Adverse Effects of Dopamine
Receptor– Blocking Agents
• Antidepressants
(amoxapine, perphenazine,
amitriptyline)
• Anti-tussives (promethazine)
• Anti-emetic(metoclopramide)
• Calcium channel blockers
(flunarizine, cinnarizine)
(Cardoso and Camargos, 1998).
Fahn R, Jankovic J. Principals and practice of movement disorders.
Philadelphia: Churchill Livingstone, 2007:280. Copyright # 2007, Elsevier.
less
common
common
in children
very rare

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Adverse effect of anti-psychotics
dopamine receptor–blocking action, either directly or secondary
metabolite.
non-receptor dopamine blocking

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MD induced by psychiatric drugs that do
not block dopamine receptors
J. H. Friedman, Movement disorders induced by psychiatric drugs that do not block
dopamine receptors, Parkinsonism and Related DisordersParkinsonism and Related Disorders 79 (2020) 60–64

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Drug -Induced Parkisonism
• Tremor, rigidity, bradykinesia, postural instability
• Indistinguishable from idiopathic PD
• Symmetric or asymmetric phenomenon.
• Subacute or chronic condition
• Caused by medications that affect presynaptic, synaptic, or
postsynaptic dopamine levels.

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Drug -Induced Parkisonism
• The most common mechanism : D2 receptor
blockade in the nigrostriatal system.
– a/w typical and atypical neuroleptic agents*
– antiemetic agents (metoclopramide & prochlorperazine)
*Adler, 1999; Armon et al, 1996; Indo and Ando, 1982

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Substances Associated With
Drug-Induced Parkinsonism
Diederich NJ, Goetz CG. Drug-induced movement disorders. Neurol Clin 1998;16:125–
139. Copyright # 1998, Elsevier

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Vids

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How frequent & who are at risk?
• 5% to 90% of patients treated depending upon the agent used
and the population studied.
• Older adult patients and females are at higher risk of
developing this syndrome.
– 50% - 70% will develop symptoms within 1 month of starting
therapy and 90% within 3 months (Ayd, 1961)

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Management
• Elimination of the offending medication
• Dat Scan
– pure drug induced parkinsonism : normalization of their
radioactive dopa uptake in the BG after elimination of
drugs
– unmasking/underlying parkinsonism : persistent
diminished uptake after elimination of the precipitating
medication
• Clinically: absence of anosmia & RBD

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Dopamine Transporter Scan ( DAT Scan)

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Acute dystonic reaction
• 2% to 3% of patients exposed to dopamine blocking
medications
• abrupt in onset
• frequently seen in a younger population, 90%
develop symptoms in the first 5 days of treatment.
• Tx: Intravenous anticholinergic or benzodiazepines

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Acute dystonic reaction
• repetitive movements of
agonist and antagonist
muscle.
• caused by medications that
block dopamine D2
receptors in the CNS.
• predominantly affect the
cranial and cervical
musculature and can be a/w
oculogyric crisis.
Medications commonly
a/w Acute Dystonic Reaction

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Tardive dyskinesia
• choreic movements
• involuntary, rapid, nonrepetitive, random, small-amplitude
movements that may be symmetric or asymmetric
• a/w chronic use, > 3 months, of dopaminergic blocking
medications
• typical and atypical neuroleptic medications (except
quetiapine and clozapine) and the antiemetic agents of
prochlorperazine and metoclopramide.

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Medications Associated with TD
Klawans HL Jr. The pharmacology of tardive dyskinesias. AmJPsychiatry1973;130:82–86.

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Vids

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Tardive dyskinesia
• Typical location is orobuccolingual, but may be generalized.
• Pathophysiology : unknown
– hypothesis is that chronic blockade of dopamine receptors may
lead to supersensitivity of the receptors --> normal dopamine
level create involuntary movement
• prevalent in older females, increases with time treated.
– A meta-analysis calculated an incidence of 20% in patients treated
with dopamine blocking agents (Kane and Smith, 1982)

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Management
• do not always extinguish
with elimination of the
offending medication
• 2% have complete and
persistent resolution of
their involuntary
movements (Glazer et al,
1990).
• medications used in the
treatment of TD

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Drug-induced chorea
• random, rapid, and of low amplitude
• acute or subacute
• generalized or hemichoreic
• a/w
– dopaminergic agents such as levodopa and, less commonly DA
– stimulants (amphetamines), OCP, antiepileptics, and some
antidepressants, drugs (cocaine)
• Incidence :not clear
• Tx: discontinuation of the offending agent

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Tardive dystonia
• focal, segmental, hemi-, or generalized.
• occurs after prolonged use (>3 months) of dopamine blocking
agents including typical and atypical neuroleptic medications
and antiemetic medications
• typical types of tardive dystonia include cranial and
• cervical disorders such as blepharospasm, opisthotonos,
retrocollis, and torticollis,

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Tardive dystonia
• incidence : 1.5% to 2% of patients treated with
dopaminergic blocking agents
• disabling and painful

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Drug-induced tremor
• rhythmic, involuntary, oscillatory movement of any
body part
• begin shortly after institution of the offending
medication.
• Type: postural, rest, or intention
• most common : enhanced physiologic tremor
• Tx: Stop offending drug. B-blocker, BDZ, Pirimidone

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Substances a/w Drug-Induced Tremor
Deuschl G, Bain P, Brin. Consensus statement of the Movement Disorder Society on Tremor.
Ad Hoc Scientific Committee. Mov Disord 1998;13(suppl 3):2–23. Copyright#1998,Movement Disorder Society.

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Akathisia
• restlessness and the irresistible urge to move.
• acute, subacute, or tardive phenomenon
• typical and atypical neuroleptic medications, antiemetic
agents, reserpine, and tetrabenazine
• Incidence 20% to 30%
• Pathophysiologic: unknown
• Mx: Reduce/stop. Propanolol, BDZ, amantadine, or clonidine,

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Medication- induced myoclonus
• sudden brief muscular
contractions
• Pathophysiology :
enhancement of
serotonin and g-
aminobutyric acid
• Mx: Stop offending drug
Substances
Associated With
Myoclonus

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Drug-induced tics
• repetitive, stereotyped motor or vocal movements (simple or
complex)
• urge to perform the movement, relief after performing the
movement, and some ability to suppress the movement for
short amounts of time
• Cranial and cervical musculature predilection but may occur in
any body location.
• caused by enhanced dopamine levels
• a/w multiple substances, including stimulants such as
methylphenidate, dextroamphetamine, pemoline, cocaine,
lamotrigine
• Mx: Stop offending drugs

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Neuroleptic Malignant Syndrome
• idiosyncratic, life-threatening syndrome
• characterized by hyperthermia, autonomic dysfunction,
mental status alteration, rigidity, or dystonia + elevation of
muscle and liver enzymes
• risk factors : gender (young males), psychomotor excitement,
refusal of food, weight loss, and high doses of a potent
neuroleptic (eg, haloperidol dose over 15 mg) (Naganuma and
Fuji, 1994).

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Neuroleptic Malignant Syndrome
• begin abruptly, fully manifested within 24 hours.
• No relationship with the duration of therapy.
• May occur soon after initiation of therapy or after prolonged
treatment.

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NMS - Tx
• Treatment is discontinuing the offending agent
• Supportive therapy.
– Dantrolene sodium
– Bromocriptine
– ICU monitoring
• Recovery can take several weeks, with residual
rigidity lasting for several months.
• Fatal in up to 20% to 30% of cases.

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Serotonin Syndrome
• may not be distinguishable in patients taking both
serotoninergic agents and neuroleptics
• ~ 15% of patients overdosing on SSRI’s syndrome develops,
within 6 h of ingestion, and almost always before 24 h.
• Features include fever, signs of spasticity, including
hyperreflexia, frequently with clonus or positive Babinski
reflexes, tremors, akathisia, rigidity, diaphoresis, dry mucous
membranes, ocular flutter, or ocular clonus , tachycardia and
labile BP.

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Serotonin Syndrome
*Clonus is the most common sign ( may be mistakenas seizure)

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Serotonin Syndrome
• Caused by serotonin toxicity affecting both central and peripheral
serotonin receptors.
• Other differential diagnostic include anti-cholinergic toxicity, withdrawal
syndromes (such as alcohol), sympathomimetic intoxication, meningitis
and encephalitis

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Serotonin Syndrome
• Treatment : symptomatic
– stopping the offending drugs
– controlling fever, blood pressure and heart rhythm,
– ICU setting, monitoring electrolytes and fluid status,
– benzodiazepines for agitation and hyper-reflexia
– Cyproheptadine, a serotonin antagonist (minimal data)

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Approach
Meticulous evaluation of History
Time at Onset
Course of disease
Drug intake/history- relation to symptoms and chronicity
Family History/Personal Social
History of other system illness
Neurological evaluation
Ancillary tests?

50. 51
Examination
 Phenomenology

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Classifications
Dopamine
vs
non-receptor dopamine
receptor–blocking action
(directly or secondary
metabolite)

52. 53
Take Home Messages
 Onset and drug history, relation to clinical symptoms are
most important
 Prevention is the most important consideration.
 The physician role:
 reassess the need for ongoing neuroleptic therapy,
 consider switching to an atypical agent (tardive dyskinesia on
newer atypical neuroleptics appears to be much lower),
 evaluate for the presence of early subtle clinical features, such as
mild pursing of the lips or rolling movements of the tongue in the
mouth.

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Thank you
sha_ray@yahoo.com