Drug induced movement

disorder
Surat tanprawate, MD, FRCP(T)
Neurological center
Chiangmai university
 +D1recepter

Basal ganglia -D2recepter

Direct pathway

Indirect pathway
 Neurotransmitter

Four classes of neurotransmitters:

1) Acetylcholine
2) Biogenic amines: serotonin, histamine, and the catecholam
ines - dopamine and norepinephrine
3) Excitatory amino acids - glutamate and aspartate, and
inhibitory amino acids - gamma-aminobutyric acid (GABA),
glycine and taurine
4) Neuropeptides, over 50 are known. Amino acid neurotrans
mitters are the most numerous
 Neuroleptic drugs

• Effects on cognition and behavior of antipsychotic drugs th

at reduce confusion, delusions, hallucinations, and psycho
motor agitation in patients with psychoses.
• 7 classes of drugs:
– Phenothiazines, further divided into the aliphatics, piperidines, an
d piperazines
– Thioxanthenes (eg, droperidol)
– Butyrophenones (eg, haloperidol)
– Dibenzoxazepines (eg, loxapine)
– Dihydroindolone (eg, molindone)
– Diphenylbutylpiperidine (eg, pimozide)
– Benzisoxazole (eg, risperidone)
 Pathophysiology:

Their therapeutic action

Antagonism of central dopaminergic

(D-2 receptor) neurotransmission

Antagonist effects at muscarinic, serotonergic,

alpha1-adrenergic, and H1-histaminergic receptors.
 Drug induced movement disorder
(DIMD)
• Excessive motor activity(hyperkinesia or dyskinesia)
– Tremor
– Myoclonus
– Chorea
– Atetosis
– Ballism
– Tics
– Dystonia
• Diminish spontaneous movement (bradykinesia)
– Parkinsonism
 Class of drugs

• Neuroleptic drug
– Typical
– Atypical
• Non-neuroleptic drug
 Neuroleptic induced movement disorder

• Acute dystonia
• Acute akathisia
• Parkinsonism
• Neuroleptic malignant syndrome
• Tardive syndrome (tardive dyskinesia)
– Buccolinguomastigatory syndrome
– Tardive stereotype
– Tardive dystonia
– Tardive tourettism
– Tardive tremor
– Tardive myoclonus
– Tardive akathisia
 Neuroleptic induced acute dystonia

• Onset
– First few day
• Drug
– Neuroleptic drug (high potency)
– metoclopamide
• Risk
– Children
– Young adult
• Pathophysiology
– Sudden imbalance between striatal dopamine VS
cholinergic system
– Relative preponderance of Ach
• Clinical
– Sustained involuntary muscle contraction
– Affect various body path
• Face, jaw, tongue, neck, throat
• Sustain deviation of the eye(oculogyric crisis)
• Limb dystonia
• Air way and respiratory muscle
• Treatment
– Drug withdrawal
– Parenteral anticholinergic: Benztropine
– Anti histamine:Diphenhydramine
– Muscle relaxant (BZD) in some case
 Neuroleptic induced akathisia
• Very common, very early, dose related SE
• Onset
– Few day
• Drug
– Neuroleptic (typical and atypical)
– Non-neuroleptic medication (SSRIs anti depressant)
– Dopamine receptor blockling drug
• Pathophysiology
– Not completely understood
– Complex interaction at the cortical-subcortical-
spinal level
Clinical
• Restlessness
– Wingging legs
– Pacing or rocking from foot to foot
– Stereotypies: involuntary movement that asr
coordinated patterned, repetitive
– Seemingly purposeful but actually purposeless
• Involve trunk, legs, lower face, tongue
• Treatment
– Lower dose or switching to a less potent
neuroleptic drugs
– BZP
– B-blocker
– Opiate
– clonidines
 Neuroleptic induced parkinsonism
• Dopamine antagonists
(neuroleptic, antiemetics)
– Phenothiazine(chlorpromazine)
– Butyrophenone(haloperidol)
– Thioxanthenes(thiothixine)
– Substituted
benzamides(metoclopramide)
• Dopamine depletors
– Reserpine
– Tetrabenazine
– Alpha-methydopa
• CCB with dopamine
agonist activity
– Flunarizine, cinnarizine
• Others
– Diltiazem, captopril
– Amiodarone, procane
– Lithium
– Phenytoin
– Fluoxetine and SSRIs
– Ara-C
– Amphotericin B
• Risk factor
– Female
– Older age
– Greater drug potency
– Higher dose
– Genetic predisposition
– Previous brain injury
• Clinical
– Identical to the idiopathic form
– Clinical may diff
• Symmetrical S/S
• Associated with Rabbit syndrome or tremor of
the mouth and jaw giving rise to peculiar
chewing motion
• Concurrent TD
 Tardive syndrome
• Onset
– Chronic(>3 Mo. of total cumulative neuroleptic
exposure)
– Occur:
• during the course of Rx
• after dose reduction (unmask TD)
• after the causative drug has been withdrawal(covert or
withdrawal TD)
• DDx with “withdrawal dyskinesia”
– Choreotic type dyskinesia
– Children
– Acute discontinuation of neuroleptic
– Short live, spontaneous remitting
• characteristic
– Persistent, sometime irriversible abnormal
movement
– Hyperkinetic type: chorea, dystonia, tics,
myoclonus, tremor
– Usually “choreic” in type
– Unaware of TD
• Region
– Orolinguomandibular, truncal, Limb region
 Pathophysiology

Long term
dopamine recepter
blockage

Increased number, affinity of

post synaptic dopamine D2 recepter
Drug that may cause Tardive dyskinesia
 Classification of Tardive dyskinesia

• Tardive dyskinesia
– Bucco-linguo-masticatory syndrome
(BLMS)
• Tardive dyskinesia varients
– Tardive dystonia
– Tardive akathisia
– Tardive myoclonus
– Tardive tics
– Tardive tremor
 Bucco-linguo-masticatory syndrome
(BLMS)
• Repetitive stereotyped movement of oral and
facial movement
– Twisting and protrusion of tongue
– lip smacking and puckering and chewing
• Sometime spread to involve trunk and
extremity
• Often uninvolved the upper face
 Tardive dystonia

• Clinical same as idiopathic dystonia

• Suspected in
• Hx. Exposure to anti-psychotic drug or
dopamine receptor blocking drug
• Exclude secondary dystonia
• Focal, segmental, generalized
 Tardive tourettism

• Motor or vocal tics

• Simple voclization
– barking, clicking noise
• Complex verbal tics
– Coprolalia, echolalia, palilalia
 Tardive akathisia

• Inability to sit still accompanied by an inner

sense of restlessness
• Fidgety, march in place
• Complex and stereotyped movement
 Tardive tremor

• Head, position, osillation

• Rabbit syndrome- 4-6Hz rhythm involve jaw,
perinasal, perioral musculature( like chewing
move of rabbit)
• Prognosis
– Persistent in most case
• Management
– Early detection
– Discontinue drugs
– Symptomatic treatment: dopamine depleting agent
• Reserpine (Serpasil)
• Metyrosine (Demser)
• Tetrabenasine (Nitoman)
– Clonazepam may useful in some case
 Others

• Phenytoin • CNS stimulant

– chorea, atetosis, – Oropharyngeal
dystonia, tremor, dyskinesia
asterixis • B-adrenergic agonists
• TCA – tremor
– Choreoatetosis, tremor, • OC
myoclonus
– chorea
• SSRIs
– Myoclonus, chorea,
dystonia, stereotype