Drug induced movement

disorders

Prepared by:
Choodamani Nepal
Senior clerkship

05/20/2024 1
Introduction
Important group of movement disorder

Hyperkinetic movement disorders

Associated with drugs that block

dopamine receptors (neuroleptics) or
central dopaminergic transmission
Movement disorders
 Chorea Postural tremor
 Phenytoin
 Theophylline
 Carbamazepine
 Amphetamines
 Caffeine
 Lithium  Lithium
 Oral contraceptives  Valproic acid
 Thyroid hormone
 Dystonia
 Dopaminergic agents
 Tricyclic
 Lithium antidepressants
 Serotonin reuptake inhibitors  Isoproterenol
 Carbamazepine
 Metoclopramide
Drug & movement disorders
Drug Category Examples Movement Disorder
Tricyclic Imipramine Tremor
Antidepressants Desipramine Gait ataxia
Amitriptyline

SSRIS Citalopram Akathisia

Escitalopram Tremor
Fluoxetine serotonin syndrome
Paroxetine
Sertraline

Antiemetics Metoclopramide Akathisisa

Droperidol Acute Dystonia
Prochlorperazine Parkinsonism
TD
NMS
Drug & movement disorders
Drug Category Examples Movement Disorder
Antipsychotics: Chlorpromazine Akathisia
Typical Fluphenazine Acute dystonia
Haloperidol Parkinsonism
Loxapine TD
Molindone NMS
Perphenazine
Trifluoperazine
Zuclopenthixol

Atypical Olanzapine Akathisia

Paliperidone Acute dystonia
Quetiapine Parkinsonism
Risperidone TD
Ziprasidone NMS
Clozapine
Drug & movement disorders
Drug Category Examples Movement Disorder
Adrenergic Agents Psychostimulants: Tremor
(Sympathomimietics) Amphetamine
Methamphetamine
Methylphenidate
Cocaine

Decongestants:
pseudoephedrine
Phenylephrine

Amiodarone Tremor
Parkinsonism
Drug & movement disorders
Drug Category Examples Movement Disorder
Dopamine depletors Reserpine Parkinsonism
tetrabenazine Akathisia

Antiepileptic agents Phenytoin Chorea with toxicity

carbamazepine

Lamotrigine Tremor
Chorea

Valproate Tremor
Parkinsonism

Lithium ` Tremor
Parkinsonism
Drugs involved
Beta adrenergic agonists
 Theophylline
 Terbutaline
 Salbutamol
 Epinephrine

Dopamine agonist
 Amphetamine
 Levodopa

Anticonvulsants
 Sodium valporate
Drugs involved
Methylxanthines
Coffee
Tea

Psychiatric drugs
Lithium
Neuroleptics
Tricyclic antidepressants

Heavy metals
Mercury
Lead
Arsenic
Pathophysiology
Complex and multifactorial

Combination of
Genetic predisposition
Dopaminergic system hypersensitivity in the basal
ganglia
Decreased functional reserve
Over activation of the cholinergic system
Postsynaptic Dopamine Receptor
Hypersensitivity Theory
Chronic blocking of presynaptic dopamine receptors
Enhances excitatory glutamatergic neurotransmission

Increasing glutamate release and extracellular

glutamate levels at corticostrial terminals
 Neurotoxic stress

Destroy the output neurons

dopaminergic hypersensitivity
Neurotoxicity Theory
Use of DRBDs increases the turnover of
neurotransmitters

Creation of free radicals that as a byproduct of

catecholamine metabolism

Neurotoxic effects to Basal ganglia

vulnerable to the effects of membrane lipid peroxidation
Dopamine-GABA Hypothesis
Due to the interaction between the dopamine and
gammaaminobutyric acid (GABA) neurons

Dopamine has both inhibitory and excitatory effects

on GABA neurons, determined by the location and
type of the dopamine receptors
Types
Acute

Subacute

Tardive syndromes( after prolonged exposure)

Acute
Most common acute hyperkinetic drug
reaction
 Dystonia

Generalized in children

Focal in adults (eg: blepharospasm, torticollis, or

oromandibular dystonia)

Develop within minutes of exposure

Acute contd…
Choreas, stereotypic behaviors, and tics  following
acute exposure to CNS stimulants such as
methylphenidate, cocaine, or amphetamines

Treatment
Parenteral administration of anticholinergics
 Benztropine or diphenhydramine
Benzodiazepines
 lorazepam, clonazepam or diazepam
Dopamine agonists
Subacute
Akathisia is the commonest reaction

Consists of motor restlessness

Treatment
Removing the offending agent
If not possible
 Benzodiazepines
 Anticholinergics
 Betablockers
 Dopamine agonists
Tardive Syndromes
Disorders develop months to years after initiation
of neuroleptic treatment

Typically composed of choreiform movements

involving the mouth, lips, and tongue

Severe cases, the trunk, limbs, and respiratory

muscles may also be affected
Tardive Syndromes
Movements are often mild and more upsetting to the
family than to the patient

Typical antipsychotics use

 higher risk of tardive dyskinesia than atypical antipsychotics

Approx 1/3rd of patients TD remits within 3 months of

stopping the drug

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Contd…
Younger patients have a lower risk of developing
neuroleptic-induced TD

Increased Risk of TD:

Elderly
Females
Those with underlying organic cerebral dysfunction
Chronic use
Use of metoclopramide for more than 12 weeks
Contd…
Treatment
Stopping the offending agent
Replacement with an atypical antipsychotic
Catecholamine depleters such as tetrabenazine
Baclofen (40–80 mg/d), clonazepam (1–8 mg/d), or valproic
acid (750–3000 mg/d)
Drug-Induced Dystonia
Twisting movement or abnormal posture
Acute or tardive involuntary limb movements
Facial grimacing
Cervical dystonia
Cculogyric crisis
Rhythmic tongue protrusion
Jaw opening or closing
Spasmodic dysphonia
Rarely stridor and dyspnea
Idiopathic Parkinson disease
Rest tremor
Bradykinesia
Rigidity
Pstural instability
Classic tardive dyskinesia
 Well coordinated continual movements of the mouth, tongue, jaw,
and cheeks (OBLD)
 Lip smacking
 Cheek puffing
 Tongue thrusting
 Jaw movements may be lateral or resemble chewing motions
 Tongue movements may be writhing or twisting (choreoathetoid)
 In addition to having OBLD, patients treated with antipsychotic
drugs may also have trunk movements
 Pelvic thrusting
 Trunk twisting
 Choreoathetotic or flicking of the extremities.
Akathisia
Literally meaning, an inability to sit
Inner feeling of restlessness
Stereotypic movements
Marching in place
Crossing and uncrossing the legs while sitting

Only drug induced movement disorder that does not

have an idiopathic counterpart
Neuroleptic malignant syndrome
Clinical Features
 Muscle rigidity
 Elevated temperature
 Altered mental status
 Hyperthermia
 Tachycardia
 Labile blood pressure
 Renal failure
 Markedly elevated creatinine kinase levels

Symptoms evolve within days or weeks after initiating the drug

Precipitated by the abrupt withdrawal of antiparkinsonian
medications in PD patients
Treatment of NMS
Immediate cessation of the offending
antipsychotic drug
Introduction of a dopaminergic agent (e.g., a
dopamine agonist or levodopa) dantrolene or a
benzodiazepine
ICU setting and includes supportive measures
Control of body temperature (antipyretics and cooling
blankets)
Hydration
Electrolyte replacement
Control of renal function and blood pressure
Serotonin syndrome
 Drugs that have serotonin-like activity (tryptophan or meperidine) or that
block serotonin reuptake
Triad of
Altered mental status
Autonomic dysfunction
Movement disorder
 Symptoms
Confusion
Hyperthermia
Tachycardia
Coma
Ataxia
Tremor
Myoclonus( prominent feature)
Contd…

Treatment
Propranolol
Diazepam
Diphenhydramine
Chlorpromazine
Cyproheptadine as well as supportive measures
Differentiating NMS vs ST
Neuroleptic Malignant Serotonin Syndrome
Syndrome
Drugs involved Drugs involved

Lab findings: -
Characteristic:
Elevated creatine kinase level, liver
function test results, white blood
cell count, coupled with a low
serum iron level
Presence of tremor
and abnormal
movements but the
absence of severe
rigidity
 Drugs associated with parkinsonism
Drugs Effects
Phenytoin chorea, dystonia, tremor,
myoclonus
Carbamazepine tics and dystonia
Tricyclic antidepressants dyskinesias, tremor, myoclonus
Fluoxetine myoclonus, chorea, dystonia
Oral contraceptives dyskinesia
β-adrenergics tremor
Buspirone akathisia, dyskinesias, myoclonus
Digoxin, cimetidine, diazoxide, dyskinesias
lithium,methadone, and fentanyl
Treatment of Drug induced
Parkinsonism
Withdrawal or dosage reduction of offending agent
If due to neuroleptic, switch to an atypical antipsychotic
Trial of amantadine, antimuscarinic agent, dopamine
agonist or levodopa
References
Harrison's Principles of Internal Medicine, 19th edition

Stewart A. Factor, DO; Joy B. Leffler, BS, MLA; Catherine

F. Murray, NASW, CSE. Drug-Induced Movement
Disorders: A clinical Review, 01/20/2009 .
www.medscape.org accessed 23th March 2016
 THANK YOU

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