What are the cardinal extrapyramidal symptoms?

Cardinal Extrapyramidal Symptoms

The cardinal extrapyramidal symptoms include acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia, which result primarily from dopamine receptor blockade in the nigrostriatal pathways. 1

Types of Extrapyramidal Symptoms

1. Acute Dystonia

• Characterized by sudden spastic contractions of distinct muscle groups, often affecting the neck, eyes (oculogyric crisis), or torso 2
• Typically occurs during the initial phases of treatment, especially with high-potency antipsychotics 2
• Risk factors include young age and male gender 2, 1
• Can be distressing and potentially life-threatening in cases of laryngospasm 2

2. Drug-Induced Parkinsonism

• Features include bradykinesia, tremors, and rigidity, mimicking idiopathic Parkinson's disease 2, 3
• Results directly from dopamine receptor blockade in the basal ganglia 1
• May be difficult to differentiate from negative symptoms of schizophrenia or catatonia 2
• Responds to anticholinergic or mild dopaminergic agents like amantadine 2

3. Akathisia

• Manifests as a subjective feeling of severe restlessness with physical agitation, frequently seen as pacing 2, 3
• Often misinterpreted as psychotic agitation or anxiety 2, 1
• A common reason for medication noncompliance 2
• Can be difficult to treat; approaches include lowering antipsychotic dose, β-blockers, or benzodiazepines 2

4. Tardive Dyskinesia

• Characterized by involuntary athetoid or choreic movements, primarily in the orofacial region but can affect any body part 2, 3
• Associated with long-term use of neuroleptics 2
• Represents a major clinical and medicolegal concern in schizophrenia treatment 2
• Can persist even after medication discontinuation 3

Pathophysiological Mechanism

• Extrapyramidal symptoms result from dopamine receptor blockade in the nigrostriatal pathways and spinal cord, disrupting normal movement control 1
• The basal ganglia, which regulate movement, are particularly affected by dopamine depletion or blockade 1, 4
• Different antipsychotics have varying risks based on their receptor binding profiles 1
• High-potency typical antipsychotics (e.g., haloperidol) carry the highest risk due to strong D2 receptor blockade 1

Clinical Considerations

• Extrapyramidal symptoms can occur in combinations, with nearly 30% of patients experiencing two or more symptoms simultaneously 5
• Common combinations include tardive dyskinesia with parkinsonism (12.9%), tardive dyskinesia with tardive dystonia (9.8%), and tardive dyskinesia with akathisia (5.2%) 5
• Hyperkinetic forms of extrapyramidal symptoms (tardive dyskinesia, tardive dystonia, and akathisia) show strong positive correlations with each other 5
• Parkinsonism has been found to be inversely related to tardive dyskinesia and tardive dystonia 5

Risk Factors

• Age: Children, adolescents, and elderly patients are at higher risk 1
• Gender: Males are at higher risk, particularly for dystonic reactions 1
• Medication properties: High-potency typical antipsychotics carry greater risk than atypical antipsychotics 1, 6
• Dosage: Higher doses and rapid dose escalation increase risk 1
• Concurrent medications: Combinations of antipsychotics or with other medications can increase risk 1, 6

Prevention and Management

• Medication selection: Consider atypical antipsychotics with lower EPS risk when possible 1
• Dosing strategy: Use the lowest effective dose and avoid rapid dose escalation 1
• Monitoring: Regular assessment for early signs of EPS is essential 1
• Treatment options include anticholinergic agents, dopaminergic agonists, and dose reduction or switching to an atypical antipsychotic 1
• Prophylactic antiparkinsonian agents may be considered for those at high risk for acute dystonia or with a history of dystonic reactions 2