What causes extrapyramidal features?

Causes of Extrapyramidal Features

Extrapyramidal features are primarily caused by dopamine receptor blockade or dopamine deficiency in the basal ganglia, with antipsychotic medications being the most common cause.

Primary Causes

Medication-Induced Extrapyramidal Symptoms

• Antipsychotic medications are the most common cause, particularly high-potency typical antipsychotics (e.g., haloperidol) which have strong dopamine D2 receptor blockade 1
• The risk varies among antipsychotics:
  • High risk: Typical/conventional antipsychotics (haloperidol, fluphenazine, thiothixene) 1
  • Moderate risk: Risperidone (at doses >2mg/day) 1
  • Lower risk: Atypical antipsychotics like olanzapine, quetiapine, clozapine 1, 2
• Other medications that can cause extrapyramidal symptoms include:
  • Antiemetics (metoclopramide, prochlorperazine) 3, 4
  • Some antidepressants 4
  • Anticonvulsants 4
  • Rarely, oral contraceptives 4

Pathophysiological Mechanism

• Dopamine receptor blockade in the nigrostriatal pathways and spinal cord disrupts normal movement control 1
• Dopamine deficiency in the basal ganglia mimics idiopathic pathologies of the extrapyramidal system 4
• Association kinetics: Newer research suggests that the association rate (how quickly drugs bind to D2 receptors) correlates more strongly with EPS risk than dissociation rate 5

Types of Extrapyramidal Symptoms

1. Acute Dystonia

• Characteristics: Sudden spastic contractions of muscle groups (neck, eyes, torso) 1
• Timing: Usually occurs within first few days of treatment 1
• Risk factors: Young age, male gender, high-potency antipsychotics 1
• Severity: Can be life-threatening in case of laryngospasm 1

2. Drug-Induced Parkinsonism

• Characteristics: Bradykinesia, tremors, rigidity 1
• Mechanism: Direct result of dopamine receptor blockade 1
• Treatment considerations: May be difficult to distinguish from negative symptoms of schizophrenia or catatonia 1

3. Akathisia

• Characteristics: Subjective feeling of restlessness, physical agitation, pacing 1
• Clinical impact: Often misinterpreted as anxiety or psychotic agitation 1
• Treatment challenges: Frequently leads to medication non-compliance 1

4. Tardive Dyskinesia

• Characteristics: Involuntary movements (facial, tongue, extremities) 1
• Timing: Associated with long-term use of antipsychotics 1
• Risk: Occurs in approximately 5% of young patients per year 1
• Persistence: May become irreversible even after medication discontinuation 6
• Variant: Respiratory dyskinesia can lead to recurrent aspiration pneumonia 1

5. Neuroleptic Malignant Syndrome

• Characteristics: Mental status changes, fever, rigidity, autonomic dysfunction 1
• Mechanism: Lack of dopaminergic activity in CNS, particularly affecting D2 receptors 1
• Severity: Potentially lethal condition requiring immediate intervention 1, 6

Risk Factors for Developing Extrapyramidal Symptoms

• Age: Children, adolescents, and elderly patients are at higher risk 1, 6
• Gender: Males have higher risk for dystonic reactions 1
• Medication properties: High-potency typical antipsychotics carry greater risk 1, 2
• Dosage: Higher doses increase risk, especially with rapid dose escalation 1, 2
• Concurrent medications: Coadministration of multiple psychotropic agents increases risk 1
• Hydration status: Dehydration increases risk 1
• Previous history: Prior EPS increases risk of recurrence 1

Clinical Impact of Extrapyramidal Symptoms

• Treatment adherence: EPS are a common reason for medication non-compliance 1, 7
• Quality of life: EPS can significantly impair functioning and quality of life 7
• Symptom masking: EPS can worsen negative symptoms, cognitive function, and mood 7
• Long-term consequences: Risk of developing irreversible tardive dyskinesia increases with duration of exposure 6

Prevention and Management Considerations

• Medication selection: Consider atypical antipsychotics with lower EPS risk when possible 1
• Dosing strategy: Use lowest effective dose and avoid rapid dose escalation 6, 2
• Monitoring: Regular assessment for early signs of EPS (every 3-6 months) 1
• Prophylaxis: Consider prophylactic antiparkinsonian agents in high-risk patients 1
• Treatment options:
  • Anticholinergic agents (benztropine) 1, 8
  • Dopaminergic agonists (amantadine) 1
  • Dose reduction or switching to an atypical antipsychotic 1
  • Beta-blockers or benzodiazepines for akathisia 1

Common Pitfalls in Diagnosis and Management

• Misdiagnosis: Akathisia often mistaken for anxiety or psychotic agitation 1
• Overtreatment: Unnecessary long-term use of antiparkinsonian agents 1
• Underrecognition: Subtle EPS may go undetected without systematic screening 1
• Respiratory dyskinesia: Often undiagnosed but can lead to serious complications 1
• Assumption of necessity: Historical misconception that EPS were necessary for antipsychotic efficacy 2