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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,

  1. Tardive Dyskinesia Mohit Bhatt Director Neurosciences Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute Mumbai, India

  2. 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%

  3. Time course DIMD Acute DIMD Tardive or delayed DIMD • Minutes to hours of drug use • 3 months drug use • Reversible • Pervasive

  4. Acute DIMD following 4 mg ondansetron (antiemetic) Acute DIMD

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

  6. Severity of Tardive syndrome Subtle Life threatening

  7. = 3 weeks of trifluoperazine (Dopamine Receptor Blocker) Subtle

  8. Drugs • Linezolide, meropenum • Anti-fungal • Metoclopramide, Ondansetron • SSRI - Escitalopram • Tramadol • NSAIDS 1 month: Renal failure + PUO Life threatening

  9. Serotonin syndrome Benzodiazepines

  10. 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

  11. Dystonic storm following sudden withdrawal of TBZ Scheinder S et al, Neurology, 2010 Aggarwal et al. Movement Disorders 2010

  12. 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

  13. DIMD • Dopamine receptor blockers § Lithium § Older antipsychotics § Antidepressants § (Newer) Atypical antipsychotics § SSRI § Dopamine depleting agents (TBZ) § Gastrointestinal drugs § Gastrointestinal drugs § Cardiac drugs § Anti-vertigo drugs § Antibiotics • Others § Anti-histaminics § Levodopa § Hormonal therapy § Anti-cholinergics § Chemotherapeutics § Anti-epileptics § Triptans

  14. Tardive syndromes - phenomenology • Oro-mandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

  15. Oro-mandibular dyskinesias • Most common DIMD • Acute or Tardive • Repetitive complex motor task § Bucco-lingual-masticatory movements § Smacking § Chewing § Fly catching § Puckering tongue movements

  16. • Tardive dyskinesia/stereotypy : Dopamine Receptor Blocker (neuroleptic)

  17. • Moderate severity TD : bon-bon tongue Haloperidol for 1 month •

  18. • Stereotypy & chorea • 3 week trifluoperazine intake and similar episode 5 y ago

  19. • Prochlorperazine for vertigo for 3 y • Tardive dyskinesia: 15 y later after stopping prochlorperazine

  20. Severe TD following 3 y of haloperidol • • Mixed movement disorder

  21. 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

  22. Tardive dyskinesia - phenomenology • Oromandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

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

  24. • Akathisia & Stereotypy with dopamine blocker + SSRI • 6 months later – OMD persists

  25. Haloperidol induced Akathisia

  26. • Akathisia, axial dyskinesia SSRI •

  27. Tardive dyskinesia - phenomenology • Oro-mandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

  28. • TBZ prescribed for OMD leading to Parkinsonism • Cinnarizine for vertigo leading to Parkinsonism

  29. 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 ”

  30. Drug Induced Parkinsonism: Treatment • Reduce dose or withdraw offending drug • Amantadine ± L- Dopa • Atypical antipsychotics safer • Prophylactic anti-cholinergic not useful

  31. Tardive dystonia - phenomenology • Oromandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

  32. • Metoclopramide taken for 1 day for augmenting lactation • Acute dystonic retrocollis, opisthotonus

  33. • Dysphagia + neck dystonia: • Metoclopramide long-term intermittent use for GI symptoms

  34. 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

  35. • Tardive dystonia • Haloperidol replaced by clozapine

  36. • Axial dystonia - dopamine • Pisa syndrome due to blocker dopamine blocker

  37. • Flupentixol induced tardive dystonia • Improvement with drug withdrawal + TBZ + BTX

  38. • 6 months later deterioration after initial improvement

  39. • Gpi DBS

  40. Tardive Tremor - phenomenology • Oromandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

  41. • Levosulpride induced Parkinsonism

  43. Tardive chorea - phenomenology • Oromandibular dyskinesia (acute, tardive) • Akathisia • Parkinsonism • Dystonia • Tremor • Chorea • Myoclonus • Rigidity and hyperthermia

  44. • Agitated Delirium: UTI + renal failure + Lithium (for bipolar disorder)

  45. • L- Dopa induced dyskinesia

  46. 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

  47. 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

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