Extrapyramidal Side Effect

Aka: Extrapyramidal Side Effect, Extrapyramidal Reaction, Extrapyramidal Effect, Drug-Induced Dyskinesia, Akinesia, Dystonic Reaction, Dyskinesia, Tardive Dyskinesia, Oculogyric Crisis

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II. Pathophysiology

  1. Typically caused by antipyschotic agents, which may over-blockade Dopaminergic Receptors
  2. Results in excess Cholinergic Activity due to a loss of typical Dopamine-mediated inhibition

III. Symptoms

  1. Akathisia
    1. Motor restlessness
    2. Differentiate medication side effect from mania or Anxiety Disorder
  2. Parkinsonian Effects (longstanding Antipsychotic use)
    1. Shuffling gait
    2. Cogwheel rigidity
    3. Psychomotor retardation
  3. Dystonias
    1. Involuntary major Muscle Contractions
    2. Acute laryngospasm may occur
    3. Spasmodic Torticollis (spasm of neck Muscles, esp. sternocleidomastoid Muscle)
    4. Oculogyric Crisis (eyes fixed, staring upward or rolling back in head)

IV. Causes: Extrapyramidal Side Effects - Antipsychotics

  1. Haloperidol (Haldol) or Haloperidol Decanoate
  2. Perphenazine (Trilafon)
  3. Thiothixene HCl (Navane)
  4. Fluphenazine HCl (Prolixin)
  5. Trifluoperazine (Stelazine)
  6. Risperidone (Risperdal)

V. Causes: Tardive Dyskinesia

  1. Antipsychotics
    1. Longterm use of high dose, high potency agents (e.g. Haloperidol)
    2. Atypical Antipsychotics
  2. Other medications (esp. Dopamine blockers)
    1. Antiparkinsonism agents (e.g. Levodopa)
    2. Metoclopramide (Reglan)
    3. Anticonvulsants (e.g. Phenytoin)
    4. Antidepressants
      1. Tricyclic Antidepressants (e.g. Amitriptyline)
      2. Serotonin Reuptake Inhibitors or SSRI (e.g. Fluoxetine, Sertraline)

VI. Adverse Effects: Reversible Extrapyramidal signs and symptoms

  1. Conditions responsive to anti-Parkinsons Agents
    1. Akinesia (lack of movement, Parkinson-like)
    2. Dystonic Reaction (facial Muscle spasm, neck, back)
    3. Dyskinesia (Blinking or twitches)
    4. Akathisia (Can not to sit still, inner restlessness)
    5. Perioral Tremor (Rabbit Syndrome)
  2. Neuroleptic Malignant Syndrome
    1. Presents as Catatonia, fever, unstable Blood Pressure
    2. Life-threatening; Stop Antipsychotic immediately

VII. Adverse Effects: Irreversible (Tardive Dyskinesia)

  1. Evaluate for these signs monthly while on Antipsychotic (see prevention as below)
  2. Higher risk in elderly, cardiovascular disease risk, HIV Infection, neurologic disorders
  3. Tardive Dyskinesia
    1. Hyperkinesia (lingual or facial)
      1. Blinking
      2. Lip smacking
      3. Sucking or chewing
      4. Rolls or protrudes Tongue
      5. Grimaces
    2. Choreoathetoid extremity movement
      1. Clonic jerking fingers, ankles, toes
    3. Tonic contractions of neck or back

VIII. Management

  1. Reversible Extrapyramidal Effects
    1. Tolerance to affect
    2. Decrease or Increase OR discontinue drug dose
    3. Shift patient to an agent without Extrapyramidal Side Effects
    4. Anticholinergic Agents may decrease Dystonia or Parkinsonism effects
      1. Benztropine (Cogentin)
      2. Antihistamine (Benadryl)
    5. Consider Beta Blockers for Akathisia
      1. Propranolol
  2. Tardive Dyskinesia
    1. Lower dose or discontinue medication
      1. Consider Clozapine as alternative Antipsychotic
    2. Avoid adding Anticholinergic Agent (e.g. Benztropine)
      1. May worsen Tardive Dyskinesia (despite benefit in acute Dystonia)
    3. Reversible Vesicular monoamine transporter 2 Inhibitors (VMAT2)
      1. Deutetrabenazine (Austedo)
      2. Ingrezza (Valbenazine)
        1. Decreases Dopamine in nerve endings
        2. Reduces symptoms by 50% with 6 weeks of treatment (Number Needed to Treat: 4)
        3. Very expensive ($5000 per month)
    4. Other symptomatic management
      1. Vitamin E supplementation
      2. Vitamin B6 Supplementation
      3. Amantadine

IX. Prevention

  1. Clinicians should be alert for Extrapyramidal Side Effects (and modify therapy to reduce adverse effects)
  2. Perform Abnormal Involuntary Movement Scale (AIMS) at least every 6 months while on Antipsychotic Medications
    1. https://dmh.mo.gov/media/21821/download

X. References

  1. (2017) Presc Lett 24(6): 36
  2. Mason, Swadron and Herbert in Herbert (2019) EM:Rap C3 3(2): 8

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