Most Common Causes of Extrapyramidal Symptoms
Antipsychotic medications, particularly high-potency typical antipsychotics like haloperidol, are the most common cause of extrapyramidal symptoms due to strong dopamine D2 receptor blockade in the nigrostriatal pathways. 1
Primary Medication Causes
Antipsychotic Medications (Most Common)
High-potency typical antipsychotics carry the highest risk:
- Haloperidol and droperidol cause the most extrapyramidal symptoms but produce less sedation compared to low-potency agents 2
- These medications block dopamine D2 receptors in the nigrostriatal pathways and spinal cord, disrupting normal movement control 1
Atypical antipsychotics have variable risk:
- Risperidone carries dose-dependent risk, particularly above 2 mg/day, with higher EPS rates than olanzapine, quetiapine, and clozapine 1, 2
- Olanzapine, quetiapine, and clozapine have the lowest risk among antipsychotics 1, 3, 4
Other Medications
Antiemetic agents are the second most common medication cause:
- Metoclopramide and prochlorperazine can cause extrapyramidal symptoms, though the risk is lower than antipsychotics 1
- Immediate withdrawal is recommended when symptoms develop with metoclopramide 1
Less common medication causes include:
- Certain antidepressants 5, 6
- Lithium 5, 6
- Various anticonvulsants 5, 6
- Rarely, oral contraceptive agents 5, 6
Pathophysiological Mechanism
The underlying mechanism involves dopamine depletion or blockade in the basal ganglia:
- Dopamine receptor blockade in the nigrostriatal pathways disrupts the balance between dopaminergic and cholinergic systems 1
- This dopamine deficiency mimics idiopathic pathologies of the extrapyramidal system 5, 6
Clinical Presentations
Four main types of extrapyramidal symptoms occur:
- Acute dystonia: Sudden spastic muscle contractions occurring within the first few days of treatment, with highest risk in young males 1, 2
- Drug-induced parkinsonism: Bradykinesia, tremors, and rigidity appearing within the first three months 1, 7
- Akathisia: Subjective restlessness and physical agitation appearing days to weeks after exposure, often misinterpreted as anxiety or psychotic agitation 1, 7
- Tardive dyskinesia: Involuntary movements associated with long-term use, with approximately 5% annual risk in young patients 1
Key Risk Factors
Patient-specific factors that increase risk:
- Young age (children and adolescents) and elderly patients are at higher risk 1, 2
- Male gender, particularly for dystonic reactions 1
- Higher medication doses and rapid dose escalation 1
- Concurrent use of multiple medications affecting dopamine pathways 1
Critical Differential Considerations
Before attributing symptoms to medications, exclude: