Basic Science Clinical
Vascular Headache Epilepsy Immunology Movement Neuromuscular Dementia Other Topics Neurosurgery
Clinical
Movement
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
Clinical › Movement

Drug-Induced Movement Disorders

Drug-Induced Movement Disorders

What Do You Need to Know?

  • 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 — bilateral, symmetric, DaTscan normal, reversible
  • Acute dystonic reaction — hours after D2 blocker; IV diphenhydramine or benztropine
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, requires CYP2D6 genotyping)
  • 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: Days to weeks (usually within 2 weeks); 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 iron
  • Stop offending agent; IV fluids, cooling, ICU monitoring
  • Dantrolene (ryanodine receptor → ↓ Ca2+) + 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.
Serotonin Syndrome

Triggers

  • Excess serotonergic activity (5-HT1A/5-HT2A); onset hours (<24 hr)
  • Combinations: SSRI + MAOI (most dangerous), SSRI + tramadol/triptan, SSRI + linezolid (weak MAOI), methylene blue, meperidine + MAOI

Classic Triad

  • Altered mental status — agitation, confusion, restlessness
  • Autonomic instability — hyperthermia, tachycardia, diaphoresis, diarrhea, mydriasis
  • Neuromuscular excitation — CLONUS is the key finding (ocular/inducible/spontaneous), hyperreflexia, tremor

Hunter Criteria

  • Serotonergic agent + one of: spontaneous clonus; inducible clonus + agitation/diaphoresis; ocular clonus + agitation/diaphoresis; tremor + hyperreflexia; temp >38°C + ocular/inducible clonus

Treatment

  • Stop serotonergic agents; cyproheptadine (5-HT2A antagonist, oral only)
  • Benzodiazepines, cooling; avoid antipyretics (muscular, not hypothalamic)
  • Resolves 24–72 hours after stopping offending agent
💎 Board Pearl
  • Clonus = serotonin syndrome; lead-pipe rigidity = NMS — the key distinction.
  • Linezolid + SSRI is a classic board trap (linezolid = weak MAOI).
  • Onset: serotonin syndrome hours vs. NMS days–weeks.
Drug-Induced Parkinsonism
  • Dopamine blockers: Typical > atypical antipsychotics; metoclopramide, prochlorperazine (commonly overlooked)
  • Also valproic acid, lithium, calcium channel blockers (flunarizine, cinnarizine)
  • Second most common cause of parkinsonism after idiopathic PD

Clinical Features

  • Bilateral and symmetric (vs. asymmetric in PD); bradykinesia/rigidity predominate; rest tremor less prominent
  • Onset weeks to months; may coexist with tardive dyskinesia

Distinguishing from PD

  • DaTscan normal (intact presynaptic neurons) vs. abnormal in PD
  • Temporal drug relationship; bilateral symmetric; reversible on withdrawal (weeks to 18 months)
Clinical Pearl
  • Always ask about metoclopramide in new parkinsonism — patients forget GI medications.
  • Normal DaTscan on neuroleptics = drug-induced parkinsonism, not PD unmasked.
Akathisia
  • Most common acute drug-induced movement disorder; onset days to weeks after D2 blocker
  • Subjective inner restlessness; cannot sit still — pacing, rocking, shifting weight
  • Subjective distress is the hallmark; can be misdiagnosed as psychotic agitation → dose increase → worsening

Treatment

  • Propranolol (lipophilic β-blocker) — first-line; benzodiazepines; mirtazapine
  • Switch to quetiapine (lower EPS risk); anticholinergics less effective than for acute dystonia
💎 Board Pearl
  • Akathisia misdiagnosed as agitation → dose increase → worsening — classic board scenario.
  • Propranolol first-line for akathisia (NOT anticholinergics).
Acute Dystonic Reaction
  • Onset hours to days after D2 blocker (90% within 5 days)
  • Risk factors: Young males, high-potency typicals, cocaine use
  • Oculogyric crisis (sustained upward eye deviation), torticollis, tongue protrusion, trismus, laryngeal dystonia (airway emergency)

Treatment

  • IV diphenhydramine or IV benztropine — immediate relief
  • Oral anticholinergic for 48–72 hours; prophylactic benztropine with high-potency antipsychotics in young patients
💎 Board Pearl
  • Oculogyric crisis + young man on haloperidol = acute dystonic reaction → IV diphenhydramine.
  • Young males = acute dystonic reactions; older females = tardive dyskinesia.
Malignant Hyperthermia
  • RYR1 mutation (AD); triggered by volatile anesthetics ± succinylcholine
  • Uncontrolled Ca2+ release from sarcoplasmic reticulum → sustained contraction, hypermetabolism
  • Early signs: Masseter rigidity, rising end-tidal CO2 (often earliest), rapidly rising temperature
  • Rhabdomyolysis, hyperkalemia, metabolic acidosis, DIC
  • Treatment: Dantrolene (ryanodine receptor inhibitor); stop volatile agents; aggressive cooling
  • Screening: Caffeine-halothane contracture test (gold standard); RYR1 genetic testing
NMS vs Serotonin Syndrome vs Malignant Hyperthermia
FeatureNMSSerotonin SyndromeMalignant Hyperthermia
CauseD2 blockers / dopamine withdrawalSerotonergic agentsVolatile anesthetics ± succinylcholine
OnsetDays to weeksHoursMinutes (intraoperative)
RigidityLead-pipeHypertonicityGeneralized
ClonusAbsentPresent (hallmark)Absent
ReflexesNormal/decreasedHyperreflexiaDecreased
PupilsNormalMydriasisNormal
CKMarkedly elevatedMild–moderateMarkedly elevated
TreatmentDantrolene + bromocriptineCyproheptadineDantrolene
GeneticNoneNoneRYR1 (AD)
💎 Board Pearl
  • Clonus = serotonin syndrome; lead-pipe rigidity = NMS; intraoperative = MH — most tested distinction.
  • Onset: MH minutes < serotonin syndrome hours < NMS days–weeks.
  • Dantrolene for NMS and MH; cyproheptadine for serotonin syndrome only.

References

  • Caroff SN, Campbell EC. Drug-induced extrapyramidal syndromes. Psychiatr Clin North Am. 2016;39(3):391-411.
  • Hauser RA, et al. KINECT 3: valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
  • Fernandez HH, et al. Deutetrabenazine for tardive dyskinesia (AIM-TD). Neurology. 2017;88(21):2003-2010.
  • Tse L, et al. Neuroleptic malignant syndrome: a clinically oriented review. Curr Neuropharmacol. 2015;13(3):395-406.
  • Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.
  • Shin HW, Chung SJ. Drug-induced parkinsonism. J Clin Neurol. 2012;8(1):15-21.
  • Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. 2005;293(23):2918-2924.