EPSEs

• Pathophysiology:

  • Defects in basal ganglia function
  • The extrapyramidal system plays a critical role in fine-tuning motor control, influencing speech, facial expressions, posture, and spontaneous motor activity
  • Antagonistic binding of dopaminergic D2 receptors within the mesolimbic and mesocortical pathways of the brain
• Overview:

  • Associated with antipsychotic medications - most commonly typical antipsychotics
  • Type of drug-induced movement disorder
  • Other drug causes - some antidepressants, lithium, anticonvulsants, and antiemetics
  • 4 common EPSEs:
  • Acute dystonia
  • Akathisia
  • Parkinsonism
  • Tardive dyskinesia
• EPSEs may be divided into 2 broad categories:

  • Hypokinetic (may resemble PD) - acute dystonia and parkinsonism
  • Hyperkinetic (may resemble Huntington's) - akathisia and tardive dyskinesia
• Acute dystonia:

  • Involuntary muscle contractions - abnormal postures or repetitive movements
  • Can be incredibly painful
  • Typically presents within 1-5 days after drug exposure
  • Can affect any skeletal muscle including the back, neck, extremities, jaw, eyes, abdominal wall, tongue muscles
  • Treatment = IM antimuscarinic e.g. benztropine, or diphenhydramine (antihistamine)
  • Benztropine blocks cholinergic receptors - balances cholinergic and dopaminergic activity
• Parkinsonism:

  • Clinical syndrome of resting tremor, cogwheel rigidity and bradykinesia
  • Due to interference of the dopaminergic pathway
  • Management = discontinuation or dose reduction of the causative medication
  • Can be switched to an atypical antipsychotic
  • Can give anticholinergic medication e.g. trihexylphenidine
  • In some cases medications used for Parkinson's disease can be used e.g. dopamine agonists and levodopa
• Akathisia:

  • Subjective feeling of internal restlessness and a compelling urge to move
  • Repetitive movements such as leg crossing, swinging, shifting from one foot to another
  • Typically presents within 4 weeks of drug exposure
  • Hard to diagnose as patients may be confused with anxiety or agitation
  • Withdrawal akathisia can also occur with the discontinuation or dose reduction of antipsychotics
  • Management - Beta blocker or benzodiazepine
  • Can be switched to atypical antipsychotic
• Tardive dyskinesia:

  • Due to long term blockage of the receptors in the nigrostriatal pathway can cause them to upregulate dopamine
  • Involuntary, choreoathetoid (rapid or slow) movements
  • Primarily affect the orofacial and tongue muscles - extends to trunk and extremities
  • Typically painless - can impact speech and swallowing
  • Can become irreversible if not treated
  • Much less common with atypical antipsychotics
  • Management - reduce dose, switch or stop medication
  • Dopamine depleting medication such as tetrabenazine