ConditionBrain & nerves
Extrapyramidal Symptoms (EPS)
Extrapyramidal symptoms (EPS) are movement problems caused mainly by medicines that block dopamine, especially antipsychotics and some anti-nausea drugs. They include sudden muscle spasms (acute dystonia), inner restlessness (akathisia), Parkinson-like stiffness and tremor (parkinsonism) and, after long-term use, involuntary movements of the face and body (tardive dyskinesia). Most early forms are treatable and reversible. Tardive dyskinesia can be persistent, so early recognition matters.
Also called: EPS, extrapyramidal side effects, drug-induced movement disorders, neuroleptic-induced movement disorders
At a glance
- What they are
- Movement side effects from drugs that block dopamine receptors.
- Main types
- Acute dystonia, akathisia, parkinsonism, tardive dyskinesia.
- Common causes
- Antipsychotics (especially older "typical" ones), metoclopramide, prochlorperazine, promethazine.
- Timing
- Hours to days (dystonia), days to weeks (akathisia, parkinsonism), months to years (tardive dyskinesia).
- Treatment
- Lower dose or switch drug, anticholinergics, beta-blockers, VMAT2 inhibitors.
When to get help
Call 911 or go to the ER
- Spasm of the throat or tongue causing trouble breathing or swallowing
- High fever, severe muscle rigidity, confusion, sweating and fast heartbeat after starting or raising an antipsychotic (possible neuroleptic malignant syndrome)
See a doctor within a day or two
- Sudden twisting of the neck, eyes rolling upward or jaw locking after a new medicine
- Severe restlessness with agitation or thoughts of self-harm. Call or text 988 (US) if you feel unsafe
Book a routine appointment
- New stiffness, slowness, tremor or shuffling walk while taking an antipsychotic or anti-nausea medicine
- Repetitive lip smacking, chewing, tongue movements or finger movements
- Restlessness that makes it hard to sit still
Why they happen
The extrapyramidal system is a network of brain circuits, centered on the basal ganglia, that controls posture and automatic movement. Dopamine is a key messenger in these circuits. Drugs that block dopamine D2 receptors disturb the balance between dopamine and acetylcholine, causing the movement problems. Long-term blockade may make receptors hypersensitive, contributing to tardive dyskinesia.
Types of extrapyramidal symptoms
| Type | Onset | What it looks like | Who is most at risk |
|---|---|---|---|
| Acute dystonia | Hours to days | Sustained muscle spasms: neck twisting (torticollis), eyes rolling up (oculogyric crisis), jaw clenching, tongue protrusion, arching of the back | Young men, high-potency antipsychotics, metoclopramide in children |
| Akathisia | Days to weeks | Inner restlessness, urge to move, pacing, rocking, shifting weight. Very distressing | Higher doses, rapid increases. Can occur with SSRIs too |
| Drug-induced parkinsonism | Weeks to months | Slowness, stiffness, tremor, shuffling walk, masked face | Older adults, women |
| Tardive dyskinesia | Months to years | Involuntary lip smacking, chewing, grimacing, tongue movements, finger or trunk movements | Older age, long-term use, women, diabetes, earlier EPS |
Other related effects include tardive dystonia, tardive akathisia and rabbit syndrome (fine lip tremor).
Medicines that cause EPS
- First-generation (typical) antipsychotics: haloperidol, fluphenazine, chlorpromazine (high risk)
- Second-generation (atypical) antipsychotics: risperidone and others carry a lower but real risk. Clozapine and quetiapine carry the lowest risk
- Anti-nausea and gut drugs: metoclopramide, prochlorperazine, promethazine, droperidol
- Others: some antidepressants, lithium, valproate (parkinsonism, tremor), and the VMAT2 blocker tetrabenazine
Diagnosis
EPS are diagnosed clinically by recognizing the pattern and linking it to the medicine. Rating scales such as the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia, the Barnes Akathisia Rating Scale and the Simpson-Angus Scale for parkinsonism are used for screening and monitoring. Guidelines recommend checking for tardive dyskinesia at least yearly in people taking antipsychotics, and more often in higher-risk patients. Doctors also rule out other causes such as Parkinson's disease, Wilson disease and Huntington disease.
Treatment
Acute dystonia
Responds within minutes to an injection of an anticholinergic such as benztropine or diphenhydramine. A short course of oral anticholinergic may follow, and the causative drug is reviewed.
Akathisia
- reduce the dose or switch to a lower-risk drug
- propranolol (a beta-blocker) is often effective
- mirtazapine or benzodiazepines in some cases
Drug-induced parkinsonism
- reduce the dose or switch to an atypical with lower risk
- anticholinergic medicines or amantadine
- symptoms usually resolve within weeks to months after the change
Tardive dyskinesia
- VMAT2 inhibitors, valbenazine and deutetrabenazine, are FDA-approved and reduce movements significantly
- review the need for the antipsychotic and consider switching to clozapine or quetiapine
- avoid anticholinergics, which can worsen tardive dyskinesia
- botulinum toxin for focal tardive dystonia
Never stop an antipsychotic abruptly without medical advice, because this can cause relapse of the underlying illness or withdrawal dyskinesia. See tardive dyskinesia for more.
Related emergency: neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare, life-threatening reaction with fever, severe "lead-pipe" rigidity, confusion, unstable blood pressure and high muscle enzymes. It needs emergency care.
Prevention
- use the lowest effective dose and increase slowly
- prefer lower-risk agents when appropriate
- limit metoclopramide use to 12 weeks or less
- regular screening for movement side effects
Frequently asked questions
What are extrapyramidal symptoms?
They are movement side effects caused mainly by dopamine-blocking medicines such as antipsychotics and certain anti-nausea drugs. They include muscle spasms (dystonia), restlessness (akathisia), Parkinson-like stiffness and tremor, and involuntary movements called tardive dyskinesia.
Which medications cause extrapyramidal symptoms?
The most common causes are antipsychotics, particularly older ones like haloperidol, and anti-nausea drugs like metoclopramide and prochlorperazine. Newer antipsychotics cause them less often. Some antidepressants, lithium and valproate can cause tremor or parkinsonism.
Are extrapyramidal symptoms permanent?
Acute dystonia, akathisia and drug-induced parkinsonism usually resolve when the medicine is adjusted or treated. Tardive dyskinesia can persist even after stopping the drug, but VMAT2 inhibitors can reduce symptoms substantially.
What does akathisia feel like?
People describe a strong inner restlessness and an urge to keep moving, with an inability to sit or stand still. They may pace, rock, or cross and uncross their legs. It can be very distressing and is sometimes mistaken for anxiety or agitation.
How is acute dystonia treated?
An injection of an anticholinergic medicine such as benztropine or diphenhydramine usually relieves the spasm within minutes. Doctors then review the medicine that caused it and may prescribe a short course of tablets to prevent recurrence.
Sources
This guide was written from current patient and clinical guidance, including:
- American Psychiatric Association: Practice Guideline for the Treatment of Patients With Schizophrenia (2020)
- National Institute of Neurological Disorders and Stroke: Tardive Dyskinesia
- MedlinePlus: Tardive dyskinesia
- NHS: Antipsychotics side effects
- StatPearls (NCBI Bookshelf): Extrapyramidal Side Effects