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11 notes available
1 Last Minute Review 2 Parkinson Disease 3 Atypical Parkinsonism 4 Tremor 5 Dystonia 6 Chorea & Ballism 7 Myoclonus 8 Tics & Tourette Syndrome 9 Wilson Disease & NBIA 10 Hereditary Ataxias 11 Drug-Induced Movement Disorders
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Drug-Induced Movement Disorders

Drug-Induced Movement Disorders

What You'll Learn

  • Tardive dyskinesia — D2 blocker exposure ≥3 months, oro-buccal-lingual stereotypies, VMAT2 inhibitors (valbenazine, deutetrabenazine)
  • NMS — lead-pipe rigidity + hyperthermia + AMS + CK elevation; dantrolene + bromocriptine
  • Serotonin syndrome — clonus (key feature) + agitation + hyperthermia; cyproheptadine
  • Akathisia — most common acute drug-induced movement disorder; propranolol first-line
  • Drug-induced parkinsonism — classically bilateral/symmetric with normal DaTscan and often reversible after withdrawal; this is a pattern, not absolute — DIP can also unmask underlying degenerative PD, and DaTscan can be abnormal in those cases
  • Acute dystonic reaction — hours to days after D2 blocker; IV diphenhydramine or benztropine
HighYield Pearls
  • NMS vs serotonin syndrome: NMS = lead-pipe rigidity, hyporeflexia, slow onset (days), after D2 blocker OR levodopa withdrawal; serotonin syndrome = clonus (LE > UE), hyperreflexia, rapid onset (hours), after serotonergic combination — clonus is the single best discriminator.
  • Drug-induced parkinsonism — typical pattern: symmetric bilateral bradykinesia/rigidity, normal DaTscan (preserved presynaptic dopamine), reversible over weeks–months after stopping offender. Frame as a pattern rather than absolute — DIP can unmask underlying degenerative PD; in those cases DaTscan can be abnormal and parkinsonism may persist or progress.
  • Anticholinergics: help acute dystonic reaction and tardive dystonia, WORSEN tardive dyskinesia — classic board distinction; avoid in elderly with DIP.
  • Acute dystonic reaction: young male, hours-days after antipsychotic/metoclopramide/prochlorperazine, oculogyric crisis + torticollis + tongue protrusion → IV/IM diphenhydramine or benztropine.
  • Tardive dyskinesia treatment: VMAT2 inhibitors — valbenazine and deutetrabenazine are FDA-approved; tetrabenazine off-label; clozapine for refractory psychosis with TD.
  • Abrupt levodopa/dopamine-agonist withdrawal in PD → NMS-like syndrome — never stop cold; taper slowly.
  • Dopamine agonist withdrawal syndrome (DAWS): depression, anxiety, dysphoria, drug craving, pain — does NOT respond to levodopa; resume DA agonist and taper more slowly.
  • Impulse control disorders (gambling, hypersexuality, shopping, binge eating) on pramipexole/ropinirole — ask every PD visit; reduce/withdraw DA agonist gradually.
  • Lithium toxicity: coarse tremor + ataxia + dysarthria + confusion ± seizures; hemodialysis if severe; chronic toxicity can cause irreversible cerebellar damage (SILENT syndrome).
  • Akathisia is the most common acute drug-induced movement disorder — subjective inner restlessness + observable pacing; propranolol first-line; do NOT mistake for psychotic agitation and uptitrate antipsychotic.
  • Drugs that worsen myasthenia gravis: aminoglycosides, fluoroquinolones, macrolides, telithromycin, β-blockers, magnesium, procainamide, quinidine, D-penicillamine, immune checkpoint inhibitors.
  • Drugs that worsen/cause parkinsonism: antipsychotics (typical > atypical), metoclopramide, prochlorperazine, valproate (especially elderly), amiodarone, lithium, tetrabenazine.
🔍 Quick ReferenceClinical · Offending drugs · Treatment
Clinical phenotype
  • Oculogyric crisis + tongue protrusion + torticollis in young male hours after Compazine → acute dystonic reaction
  • Lead-pipe rigidity + hyperthermia >40°C + AMS + CK >10,000 → NMS
  • Clonus (LE > UE) + hyperreflexia + diaphoresis + diarrhea + agitation → serotonin syndrome
  • Oro-buccal-lingual chewing/lip-smacking/tongue-rolling after years on antipsychotic → tardive dyskinesia
  • Retrocollis + sustained postures after chronic neuroleptic → tardive dystonia
  • Inner restlessness, can’t sit still, pacing days after starting risperidone → akathisia
  • Symmetric bilateral bradykinesia/rigidity, NORMAL DaTscan → drug-induced parkinsonism
  • Coarse postural tremor + ataxia + dysarthria + confusion → lithium toxicity
  • New-onset gambling/hypersexuality in PD patient → impulse control disorder on DA agonist
  • Punding, compulsive levodopa use, hypomania in PD → dopamine dysregulation syndrome
Offending drugs / mechanism
  • Haloperidol, fluphenazine, metoclopramide, prochlorperazine (D2 blockers) → acute dystonia, NMS, akathisia, TD, DIP
  • SSRI + MAOI / tramadol / linezolid / fentanyl / methylene blue → serotonin syndrome
  • Abrupt levodopa or DA-agonist withdrawal in PD → NMS-like syndrome / DAWS
  • Pramipexole, ropinirole, rotigotine → impulse control disorders, DAWS on taper
  • Lithium, valproate (dose-related), β-agonists, amiodarone, SSRIs, TCAs, theophylline, prednisone → drug-induced action/postural tremor
  • Valproate (especially elderly), amiodarone, lithium, tetrabenazine → drug-induced parkinsonism
  • Aminoglycosides, fluoroquinolones, macrolides, β-blockers, magnesium, D-penicillamine, checkpoint inhibitors → worsen myasthenia gravis
Treatment / management pearls
  • IV/IM diphenhydramine or benztropine → acute dystonic reaction
  • Stop neuroleptic + IV fluids + cooling + dantrolene + bromocriptine/amantadine → NMS
  • Stop serotonergic + cyproheptadine + supportive care → serotonin syndrome
  • Propranolol (first-line), benzodiazepines, mirtazapine → akathisia
  • Valbenazine or deutetrabenazine (VMAT2 inhibitors) → tardive dyskinesia
  • Anticholinergics (trihexyphenidyl), botulinum toxin, GPi DBS → tardive dystonia (anticholinergics WORSEN TD)
  • Withdraw offender + amantadine bridge; avoid anticholinergics in elderly → drug-induced parkinsonism
  • Discontinue lithium + hemodialysis if severe/≥4 mEq/L or symptomatic → lithium toxicity
  • Reduce/withdraw DA agonist gradually; screen at every PD visit → impulse control disorders
  • Resume DA agonist and taper more slowly (does NOT respond to levodopa) → dopamine agonist withdrawal syndrome
Tardive Dyskinesia

Definition & Mechanism

  • Tardive = “late-onset” — prolonged D2 receptor blocker exposure
  • Minimum exposure: ≥3 months (or ≥1 month if age >60)
  • Pathophysiology: Dopamine receptor upregulation/supersensitivity from chronic D2 blockade
  • Offending agents: Typical > atypical antipsychotics; metoclopramide, prochlorperazine

Clinical Features

  • Oro-buccal-lingual stereotypies (most common) — chewing, lip smacking, tongue protrusion/rolling
  • Choreiform movements of limbs/trunk; respiratory dyskinesias
  • Repetitive and stereotyped (unlike chorea, which is random and flowing)

Risk Factors & Treatment

  • Risk factors: Older age (strongest), female, longer exposure, higher dose, African American descent
  • Step 1: Stop/switch offending agent (quetiapine or clozapine — lowest TD risk)
  • Step 2: VMAT2 inhibitors — valbenazine (FDA-approved, once-daily) or deutetrabenazine (FDA-approved); tetrabenazine (off-label for TD, requires CYP2D6 genotyping at doses >50 mg/day)
  • May be irreversible; anticholinergics worsen TD — avoid
💎 Board Pearl
  • Anticholinergics worsen TD but help acute dystonic reactions and tardive dystonia — critical board distinction.
  • Do NOT abruptly stop the neuroleptic — withdrawal can worsen TD (“withdrawal dyskinesia”).
Tardive Dystonia
  • Sustained postures (not stereotyped movements); affects younger patients; more disabling, less likely to remit than TD
  • Retrocollis (backward neck pulling) — characteristic (vs. anterocollis in idiopathic cervical dystonia)
  • Trunk extension (opisthotonos), limb dystonia; can coexist with TD

Treatment

  • Anticholinergics (trihexyphenidyl) — helpful (unlike TD where they worsen symptoms)
  • Botulinum toxin for focal dystonia; DBS (GPi) if refractory; VMAT2 inhibitors may help
💎 Board Pearl
  • Retrocollis after chronic neuroleptic use = tardive dystonia.
  • Tardive dystonia responds to anticholinergics; tardive dyskinesia does NOT.
Neuroleptic Malignant Syndrome

Mechanism & Triggers

  • Central D2 blockade or dopamine withdrawal (abrupt levodopa cessation)
  • Onset: 24–72 hours (within 2 weeks of drug initiation/dose change); idiosyncratic, not dose-dependent

Classic Tetrad

  • Lead-pipe rigidity (NOT cogwheel)
  • Hyperthermia — often >40°C; from muscle rigidity generating heat
  • Altered mental status — confusion to coma
  • Autonomic instability — tachycardia, labile BP, diaphoresis

Labs & Treatment

  • CK markedly elevated (>1,000, often >10,000); leukocytosis; metabolic acidosis; renal failure (myoglobinuria); low serum iron (supportive but non-specific)
  • Stop offending agent; IV fluids, cooling, ICU monitoring
  • Dantrolene (ryanodine receptor inhibitor → ↓ sarcoplasmic Ca2+ release) + bromocriptine/amantadine (D2 agonists)
  • Avoid succinylcholine (hyperkalemia risk); mortality 5–10%
💎 Board Pearl
  • Lead-pipe rigidity + hyperthermia + CK >1,000 + recent antipsychotic change = NMS.
  • Abrupt levodopa withdrawal in Parkinson patient can trigger NMS — classic board scenario.
🔒

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