Toxicology – Extrapyramidal Side Effects (EPS)

Definition

Extrapyramidal side effects are drug-induced movement disorders caused mainly by dopamine-blocking medications. They can occur at normal therapeutic doses.

Common Causes

EPS can occur with many antipsychotic drugs, but they are more common with first-generation (typical) antipsychotics, especially:

• Butyrophenones
• Phenothiazines

They may also occur with other dopamine-blocking drugs.

Mechanism of Action

EPS result from dopamine D₂ receptor blockade in the basal ganglia, especially within the nigrostriatal pathway.

Reduced dopamine activity disrupts normal motor control and produces several characteristic movement disorders.

Clinical Features

The type of EPS often depends on how long the patient has been taking the medication.

• Acute dystonia: Usually occurs early. Causes sustained involuntary muscle contractions, abnormal posturing, neck or facial spasms, and sometimes tongue or jaw involvement.
• Akathisia: A feeling of intense inner restlessness with an inability to remain still.
• Drug-induced parkinsonism: May develop after weeks to months and can cause bradykinesia, shuffling gait, tremor, and cogwheel rigidity.
• Tardive dyskinesia: Usually appears after prolonged treatment and causes repetitive involuntary movements, especially of the mouth, lips, tongue, and face. It may persist even after the drug is stopped.

Management

Treatment depends on the specific movement disorder.

Common approaches include:

• Reducing or stopping the offending medication when appropriate
• Diphenhydramine or benztropine for acute dystonia and some parkinsonian symptoms
• Benzodiazepines in selected cases
• Beta-blockers such as propranolol for akathisia

Tardive dyskinesia requires a different long-term management approach and may be treated with medications that reduce abnormal dopamine signaling, such as VMAT2 inhibitors.

Key Points

• EPS are caused by dopamine blockade in the basal ganglia.
• Acute dystonia and akathisia tend to occur early.
• Parkinsonism usually develops later.
• Tardive dyskinesia is associated with long-term exposure and may be irreversible.
• EPS and neuroleptic malignant syndrome can both occur during therapeutic antipsychotic use, but NMS is distinguished by fever, autonomic instability, altered mental status, and severe rigidity.