Extrapyramidal Effects of Drugs (EPS)

Why these drugs cause movement problems

The extrapyramidal system is a network in the brain, centered on the basal ganglia, that controls posture and automatic movements. It depends on a balance between dopamine and acetylcholine. Drugs that block dopamine D2 receptors tilt that balance, causing abnormal movements, much as dopamine loss does in Parkinson's disease.

Medicines that cause EPS

Types of extrapyramidal side effects

Acute dystonia

Sudden, sustained muscle contractions causing abnormal postures, usually within hours to 5 days of starting or increasing a drug:

• twisting of the neck (torticollis) or back arching
• eyes rolling upward (oculogyric crisis)
• jaw clenching, tongue protrusion, difficulty speaking or swallowing
• rarely, throat spasm (laryngeal dystonia), which is life-threatening

It is most common in young men and with high-potency antipsychotics or IV anti-nausea drugs. It responds within minutes to an injection of an anticholinergic (benztropine) or antihistamine (diphenhydramine).

Akathisia

An intense inner restlessness with an urge to move, appearing within days to weeks:

• inability to sit still, pacing, rocking or shifting weight from foot to foot
• crossing and uncrossing legs
• anxiety, irritability and distress

Akathisia is often mistaken for worsening anxiety or psychosis. It is linked to agitation and, in some people, suicidal thoughts, so it should be recognized and treated. Treatments include lowering the dose, switching drug, propranolol, mirtazapine or benzodiazepines.

Drug-induced parkinsonism

Symptoms similar to Parkinson's disease, usually within weeks to months:

• slow movements and reduced facial expression
• muscle stiffness
• shuffling walk and reduced arm swing
• tremor at rest, often on both sides

It is the second most common cause of parkinsonism after Parkinson's disease, and more common in older adults. It usually improves within weeks to months after stopping or reducing the drug, though occasionally it reveals underlying Parkinson's disease.

Tardive dyskinesia

Tardive dyskinesia develops after months or years of treatment:

• repetitive movements of the mouth, lips and tongue (lip smacking, chewing, tongue darting)
• grimacing and blinking
• finger, toe and trunk movements

It can persist after the drug is stopped and may temporarily worsen on withdrawal. Risk increases with age, total exposure, female sex and diabetes. VMAT2 inhibitors (valbenazine, deutetrabenazine) are approved treatments. Anticholinergics do not help and may worsen it.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is a rare, life-threatening reaction with high fever, severe rigidity, confusion and unstable blood pressure and heart rate. It needs emergency care.

Diagnosis

EPS is diagnosed by recognizing the movement pattern and linking it to a medicine. Doctors review all drugs, timing, doses and recent changes. Standard rating scales (such as the AIMS for tardive dyskinesia, the Barnes scale for akathisia and the Simpson-Angus scale for parkinsonism) track severity. Brain imaging is rarely needed but may be used if another condition is suspected.

Treatment and prevention

• Use the lowest effective dose of antipsychotic and the lowest-risk drug that works.
• Switch to an antipsychotic with lower EPS risk, such as quetiapine or clozapine when appropriate.
• Avoid long-term metoclopramide use; the FDA advises against use beyond 12 weeks except in rare cases.
• Specific treatments: anticholinergics for dystonia and parkinsonism; propranolol for akathisia; VMAT2 inhibitors for tardive dyskinesia.
• Regular monitoring: your prescriber should check for abnormal movements at the start and regularly during treatment.
• Never stop antipsychotics abruptly without guidance, as this can cause relapse of the underlying illness and withdrawal movements.

Frequently asked questions

What are extrapyramidal side effects?

They are movement problems caused by medicines that block dopamine, mainly antipsychotics and some anti-nausea drugs. They include acute dystonia (muscle spasms), akathisia (restlessness), drug-induced parkinsonism (stiffness, tremor, slowness) and tardive dyskinesia (involuntary repetitive movements).

Are extrapyramidal side effects permanent?

Acute dystonia, akathisia and parkinsonism usually resolve when the medicine is reduced, switched or stopped. Tardive dyskinesia can be long-lasting or permanent, but VMAT2 inhibitors can reduce symptoms.

What does akathisia feel like?

People describe a powerful inner restlessness and an inability to stay still, with pacing, rocking or constant leg movements, often with anxiety or irritability. It can be very distressing and should be reported to your prescriber promptly.

Which antipsychotics have the lowest risk of EPS?

Clozapine and quetiapine have the lowest risk. Most other second-generation antipsychotics have lower risk than older drugs such as haloperidol, but risk rises with higher doses.