Tardive Dyskinesia Mohit Bhatt Director Neurosciences Kokilaben - - PowerPoint PPT Presentation

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Tardive Dyskinesia Mohit Bhatt Director Neurosciences Kokilaben - - PowerPoint PPT Presentation

Feb 04, 2024 1.06k likes •1.6k views

Tardive Dyskinesia Mohit Bhatt Director Neurosciences Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute Mumbai, India Drug Induced Movement Disorders (DIMD) 1950s Introduction of Chlorpromazine (anti-psychotic,

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Tardive Dyskinesia

Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute Mumbai, India

Mohit Bhatt

Director Neurosciences

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Drug Induced Movement Disorders (DIMD)

  • 1950s Introduction of Chlorpromazine (anti-psychotic, neuroleptic)
  • DIMD- Hypokinetic and hyperkinetic movement disorders
  • Drugs:

§ Typical antipsychotics (post-synaptic dopamine receptor blocking agents)- haloperidol § Newer (atypical) antipsychotics: risperidone, olanzapine § Non-Psychiatric dugs

  • Prevalence: 17-30%, up to 60%
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Time course DIMD

Acute DIMD

  • Minutes to hours of drug use
  • Reversible

Tardive or delayed DIMD

  • 3 months drug use
  • Pervasive
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Acute DIMD following 4 mg ondansetron (antiemetic) Acute DIMD

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Tardive dystonia following 3 years of haloperidol for Rheumatic chorea Tardive or delayed

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Severity of Tardive syndrome

Subtle Life threatening

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=

3 weeks of trifluoperazine (Dopamine Receptor Blocker) Subtle

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1 month: Renal failure + PUO Drugs

  • Linezolide,

meropenum

  • Anti-fungal
  • Metoclopramide,

Ondansetron

  • SSRI - Escitalopram
  • Tramadol
  • NSAIDS

Life threatening

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Serotonin syndrome Benzodiazepines

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Red flags for Tardive Dyskinesia

  • Acute or rapid onset of movement disorder
  • Mixed movement disorder
  • Oro-mandibular movements
  • Axial involvement
  • Drugs for psychiatric, gastrointestinal disorders and vertigo
  • Sudden withdrawal of dopamine receptor blockers
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Dystonic storm following sudden withdrawal of TBZ

Scheinder S et al, Neurology, 2010 Aggarwal et al. Movement Disorders 2010

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Importance of Tardive syndromes

  • Early diagnosis crucial

§ Innocuous, not readily reported by patients, not recognized by doctors § Symptoms not attributed to drug – drug continued

  • Tardive syndromes often intractable
  • Morbidity and mortality
  • Can be avoided

§ Safer alternatives § Avoid unsupervised use

Aggarwal and Bhatt. Handbook of Clinical Neurology. 2014

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DIMD

  • Dopamine receptor blockers

§ Older antipsychotics § (Newer) Atypical antipsychotics § Dopamine depleting agents (TBZ) § Gastrointestinal drugs § Anti-vertigo drugs

  • Others

§ Levodopa § Anti-cholinergics § Anti-epileptics § Triptans § Lithium § Antidepressants § SSRI § Gastrointestinal drugs § Cardiac drugs § Antibiotics § Anti-histaminics § Hormonal therapy § Chemotherapeutics

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Tardive syndromes - phenomenology

  • Oro-mandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia
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Oro-mandibular dyskinesias

  • Most common DIMD
  • Acute or Tardive
  • Repetitive complex motor task

§ Bucco-lingual-masticatory movements § Smacking § Chewing § Fly catching § Puckering tongue movements

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  • Tardive dyskinesia/stereotypy : Dopamine Receptor Blocker

(neuroleptic)

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  • Moderate severity TD : bon-bon tongue
  • Haloperidol for 1 month
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  • Stereotypy & chorea
  • 3 week trifluoperazine intake and similar episode 5 y ago
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  • Prochlorperazine for vertigo for 3 y
  • Tardive dyskinesia: 15 y later after stopping prochlorperazine
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  • Severe TD following 3 y of haloperidol
  • Mixed movement disorder
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Risk factors for Tardive Dyskinesia

  • Age
  • Women > Men
  • Cumulative drug exposure – duration & dosage
  • Alcohol, diabetes, cocaine
  • ECT
  • Continuation of dopamine blocking agents
  • Concomitant use – anticholinergic drugs, lithium
  • Genetic predisposition

Bhatt et al. In: Drug induced movement disorders. Marcel Dekker, NY. 2004

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Tardive dyskinesia - phenomenology

  • Oromandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia
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Akathisia

  • Motor
  • Pacing
  • Body rocking
  • Crossing uncrossing legs
  • Folding unfolding arms
  • Foot tapping
  • Hand rubbing
  • Face rubbing
  • Subjective
  • Anxiety
  • Impending doom
  • Agitation
  • Violence
  • Suicide
  • Irritability
  • Impatience
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  • Akathisia &

Stereotypy with dopamine blocker + SSRI

  • 6 months later – OMD persists
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Haloperidol induced Akathisia

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  • Akathisia, axial dyskinesia
  • SSRI
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  • Oro-mandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia

Tardive dyskinesia - phenomenology

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SLIDE 28
  • TBZ prescribed for OMD

leading to Parkinsonism

  • Cinnarizine for vertigo leading to

Parkinsonism

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Drug Induced Parkinsonism

  • Dopamine depletors: reserpine, TBZ
  • Convectional dopamine blockers:

§ Neuroleptics: chlorpromazine, haloperidol § SSRI, Lithium

  • Inapparent dopamine blockers

§ Prokinetics, anti-emetics and : Metoclopramide, levosulpride § Anti-vertigo medications: flunarizine, cinnarizine § Calcium channel blockers, anti-arrhythmics § Valproate

  • Other Mechanism

§ Osmotic disequilibrium: diuretics, angiotensin receptor blocker § “Alternative medicines”

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Drug Induced Parkinsonism: Treatment

  • Reduce dose or withdraw offending drug
  • Amantadine ± L- Dopa
  • Atypical antipsychotics safer
  • Prophylactic anti-cholinergic not useful
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Tardive dystonia - phenomenology

  • Oromandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia
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  • Metoclopramide taken for 1 day for augmenting lactation
  • Acute dystonic retrocollis, opisthotonus
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  • Dysphagia + neck dystonia:
  • Metoclopramide long-term intermittent use for GI symptoms
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Metoclopramide

  • US FDA – Black box warning – restricts use to < 12 weeks
  • Second most common to induce tardive dyskinesia after

haloperidol

  • Accounts for third of all DIMD
  • 71% TD persistent despite drug withdrawal

Aggarwal and Bhatt. Handbook Of Clinical Neurology. 2013

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  • Tardive dystonia
  • Haloperidol replaced by clozapine
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  • Axial dystonia - dopamine

blocker

  • Pisa syndrome due to

dopamine blocker

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  • Flupentixol induced

tardive dystonia

  • Improvement with

drug withdrawal + TBZ + BTX

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  • 6 months later deterioration after initial improvement
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  • Gpi DBS
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Tardive Tremor - phenomenology

  • Oromandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia
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  • Levosulpride induced

Parkinsonism

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Tardive chorea - phenomenology

  • Oromandibular dyskinesia (acute, tardive)
  • Akathisia
  • Parkinsonism
  • Dystonia
  • Tremor
  • Chorea
  • Myoclonus
  • Rigidity and hyperthermia
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  • Agitated Delirium: UTI + renal failure + Lithium (for

bipolar disorder)

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  • L- Dopa induced dyskinesia
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Tardive dyskinesia

  • Range of hypokinetic and hyperkinetic movement disorders
  • Can be pervasive
  • Drugs:

Medicines for psychiatric disorders: typical> atypical antipsychotics Non-Psychiatric dugs

  • Consider safer alternatives
  • Early diagnosis + discontinue offending drug
  • Warn about unsupervised use
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Treatment of Tardive syndromes

  • Prevention
  • Safer alternatives
  • Prefer newer Dopamine blocking agents
  • Botulinum toxin- focal dystonia
  • Tetrabenazine/ Valbenazine/ Deutetrabenazine-

dystonia, chorea, OMD

  • L-dopa – Parkinsonism
  • Gpi- DBS – Dystonia, TD