Extrapyramidal symptoms

🧠 About

• Always check the BNF or equivalent for up-to-date prescribing advice.
• Extrapyramidal side effects (EPS) occur with drugs that cause central dopamine blockade, particularly in the basal ganglia.
• Older “typical” antipsychotics (e.g. haloperidol) are more likely to cause EPS than newer “atypical” agents.
• Women and older adults are more susceptible - possibly due to reduced dopaminergic reserve and altered drug metabolism.
• EPS can be profoundly distressing and may increase risk of depression, suicidality, anxiety, and substance misuse.

💊 Common Causes

• Typical antipsychotics: Chlorpromazine, Haloperidol.
• Atypical antipsychotics: Risperidone, Olanzapine (less common, dose-related).
• Antiemetics: Metoclopramide, Prochlorperazine.
• Any drug causing significant D2 receptor blockade in the nigrostriatal pathway.

⚙️ Aetiology & Pathophysiology

• EPS result from D2 receptor blockade in the nigrostriatal pathway - disrupting the fine balance between dopaminergic and cholinergic activity.
• Dopamine normally inhibits acetylcholine; blocking D2 receptors therefore produces a relative cholinergic excess → abnormal motor output.
• The basal ganglia circuits involved mirror those affected in idiopathic Parkinson’s disease, hence the clinical similarity.

🩺 Clinical Syndromes

• Acute Dystonia: Involuntary sustained muscle contractions (often torticollis, oculogyric crisis). Occurs hours to days after exposure; more common in young men.
• Akathisia: A subjective sense of inner restlessness; patients may pace or rock. Can appear within days to weeks. Often misinterpreted as agitation or anxiety.
• Drug-Induced Parkinsonism: Rigidity, bradykinesia, tremor, postural instability. Typically bilateral and symmetric, unlike idiopathic Parkinson’s disease. May include “rabbit syndrome” (perioral tremor).
• Tardive Dyskinesia: Late-onset, often irreversible repetitive movements (lip-smacking, tongue protrusion, grimacing). Results from chronic dopamine receptor upregulation and supersensitivity.

🧩 Management Principles

• 🎯 Identify and stop or switch the offending drug (e.g. to quetiapine or clozapine if psychiatric stability allows).
• ⚕️ Acute dystonia: Treat with IM/IV Benztropine or Procyclidine. Symptoms usually resolve within minutes.
• 💤 Akathisia: Dose reduction, or add a benzodiazepine (e.g. lorazepam) or propranolol (non-selective β-blocker).
• 🦵 Drug-induced Parkinsonism: Consider anticholinergics (procyclidine) or amantadine; avoid levodopa as it may worsen psychosis.
• 😣 Tardive dyskinesia: Gradually withdraw the drug if feasible; switch to an atypical agent. VMAT-2 inhibitors (e.g. valbenazine, tetrabenazine) may be considered under specialist supervision.
• ❗ Avoid abrupt discontinuation - psychiatric relapse risk is high. Always taper under specialist review.

📚 References

• NICE NG222: Medicines associated with movement disorders (2023)
• BNF – Extrapyramidal Side Effects section
• Katzung BG. Basic & Clinical Pharmacology, 15th ed. – Chapter on Antipsychotic Agents
• British Journal of Psychiatry, 2022; 221(5): Motor Adverse Effects of Antipsychotics.