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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