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Extrapyramidal Symptoms (EPS): Approach in Primary Care

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Sommaire : While antipsychotic medications can be extremely helpful for certain symptoms such as psychosis, they can unfortunately cause various side effects including extrapyramidal symptoms (EPS). Management strategies include giving diphenhydramine for acute dystonia; stopping or reducing the dose of antipsychotic; switching to a second generation; using a lower risk second generation antipsychotic such as quetiapine.
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Case, Part 1 

D. is a 20-yo male in your practice. He was recently admitted to hospital for a brief psychotic episode and while in hospital was started on risperidone. He was discharged and is seeing you in follow-up. While his psychosis symptoms have improved and he is functioning much better, he is brought in for a same-day visit by his parents. He complains of neck stiffness and troubles moving his eyes...

Pathophysiology of EPS 

Beneficial antipsychotic effects and extrapyramidal effects are due to binding to D2 receptors in the central nervous system. 


Antipsychotic effects occur at 60-80% of D2 occupancy.


Acute EPS effects occur at 75-80% of D2 occupancy.


In other words, there is a very margin between therapeutic effects and extrapyramidal effects.


Though less frequent agents that block central dopaminergic receptors may also cause EPS (D’Souza, 2019) such as: 

  • Anti-emetics (metoclopramide, droperidol, and prochlorperazine) 
  • Lithium
  • Serotonin reuptake inhibitors (SSRIs) 
  • Stimulants
  • Tricyclic antidepressants (TCAs)

Risk Factors for EPS

Highest risk medications 

  • First-generation antipsychotic drugs (“typical antipsychotics”) such as 
    • Haloperidol
    • Chlorpromazine
    • Prochlorperazine 

Lower risk medications (SGAs) 

  • Second-generation antipsychotics (“atypical antipsychotics), with an atypical mechanism of action, are felt to be at a lower risk of EPS.  
  • Higher risk SGAs 
    • Risperidone > compared to clozapine, olanzapine, quetiapine, ziprasidone.
    • Ziprasidone >  compared to olanzapine and quetiapine. 
    • Zotepine >  compared to clozapine.

Neutral risk 

  • No significant difference between amisulpride and its comparators (olanzapine, risperidone, or ziprasidone).

Lowest risk 

  • Quetiapine (when compared with (olanzapine, risperidone, and ziprasidone). 
  • Clozapine 

Physical Exam

Ask the patient to remove any gum or objects from their mouth. 


Head / neck / cranial nerves: 

  • Impaired extraocular movements?
  • Sustained gaze deviation (oculogyric crisis)? 
  • Abnormal movements of the face, mouth, lips, jaw or tongue? 

Excessive salivation (sialorrhea)


Motor examination: 

  • Increased or a rigid tone?
  • Cogwheeling? 
  • Abnormal movements present?
  • Abnormal movement at rest? (dyskinesias)
  • Restless with a constant need to move or pace? (akathisia)
  • Abnormal postures? (dystonia)
  • Tremor?


  • Movements slowed? 
  • Trouble with rapid alternating movements? 
  • Slow to stand from a seated position? 



  • Shuffling gait? 
  • Postural instability?

Mental Status Examination (MSE)



Alert and oriented with EPS

Changes in level of consciousness suggest other causes, e.g. neuroleptic malignant syndrome

Normal attention, memory, executive function 


Decreased facial expression or a ‘mask-like facies? 


Slow to move or speak? (bradykinesia)

Dysarthria or dysphonia? 


Vital signs should be normal with EPS. 

Are vital signs abnormal? Consider neuroleptic malignant syndrome (NMS) or other conditions instead. 

Rating Scales

Standardized rating scales include:

  • Extrapyramidal Symptom Rating Scale (Gharabawi, 2005). 


There are no laboratory nor imaging tests. 

Management of EPS

Early EPS


Onset of early EPS 

  • Occurs within few weeks of starting new medication, or increasing dosage. 

Prognosis of early EPS 

  • Symptoms reversible when antipsychotic is stopped 
  • Serious negative impact on medication adherence 

Type of  EPS 


Management / Treatment 

Acute dystonia

Sustained abnormal postures and muscle spasms, especially of the head or neck


  • Retrocollis: Neck spasms caused by neck extension 
  • Extension of trunk 
  • Eye deviation
  • Forced jaw opening
  • Tongue protrusion
  • Torticollis: Spasm of neck muscles, causing abnormal neck position. 
  • Trismus: Spasm of jaw muscles, usually forcing jaw closed
  • Laryngospasm: Spasm of vocal cords making it difficult to speak or breathe
  • Oculogyric crisis: Forced upward deviation of the eyes. 

DDx muscle rigidity / tension

  • Muscle rigidity and tension are nonspecific symptoms that may be observed in neuroleptic malignant syndrome, serotonin syndrome, and other movement disorders. 

Stop antipsychotic


Anticholinergic medications such as 

  • Benztropine 
  • Biperiden 
  • Diphenhydramine (Benadryl) 

May relieve symptoms within minutes; repeat doses may be required if no response is seen within 30 min. 


May need to be IV / IM -- symptoms resolve within minutes with parenteral therapy. 


Tell patients/ families that if the patient has an acute dystonic reaction, they can give an oral dose of over-the-counter diphenhydramine (Benadryl) until they are able to see a professional. 


Is it a laryngeal or pharyngeal dystonic reaction?

  • If so, assess if emergency airway intervention is necessary
  • Contact Emergency Medical Services (EMS) for transfer to Emergency Department (ED) 

Is an antipsychotic absolutely required?

  • If the causative agent was a first-generation antipsychotic (FGA), then switch to a second-generation antipsychotic (SGA)
  • If already on SGA, switch to SGA with the least risk, e.g. Quetiapine or Clozapine. 

Pseudoparkinsonism aka drug-induced parkinsonism

Resemble parkinsonism

Tremulousness in the hands and arms, rigidity in the arms and shoulders, bradykinesia, akinesia, hypersalivation, masked facies, and shuffling gait

Stop or reduce the dosage of antipsychotic


Switch to an atypical antipsychotic


Give Parkinson medications such as (Shin, 2012):

  • Amantadine
  • Antimuscarinic agents
  • Dopamine agonists
  • Levodopa


Excessive restlessness with a need to move, e.g. pacing 

Symptom relief is achieved with movement.

Patients report feelings of inner tension or restlessness. 

Movements such as shaking or rocking of the legs and trunk, pacing, marching in place, rubbing the face or moaning to relieve their discomfort. 

Young children not always able to explain akathisia; may describe vague sensations of internal restlessness, discomfort or anxiety

Parents may report their child is more anxious, or irritable/agitated.


DDx Akathisia 

  • Anxiety 
  • Agitation in a patient with psychosis 

Stop or reduce the dosage of causative antipsychotic


Beta-adrenergic blockers (such as propranolol (Inderal) at 20-80 mg / day).

















Late EPS

  • Occurs after chronic, long-term or prolonged treatment (after several months). 
  • Serious negative impact on quality of life. 


Type of Later EPS 



Tardive dyskinesia 

Involuntary choreoathetoid movements affecting orofacial and tongue muscles (e.g. grimacing, tongue protruding, lips puckering)

Less frequently torso and limb movements

Cause difficulty with chewing, swallowing, talking 


DDx chorea and athetosis 

  • Huntington’s disease (distinguished based on family history and genetic testing), 
  • Sydenham’s chorea (identified with a history of streptococcal infection),
  • Wilson disease (adolescent-onset with a defect in copper metabolism), 
  • Cerebrovascular lesions

Stop the offending agent 

Switching to one with a lower risk

  • Benzodiazepines
  • Amantadine
  • Dopamine-depleting medications (e.g. tetrabenazine)

Neuroleptic-induced parkinsonism

Tremor, skeletal muscle rigidity, bradykinesia


DDx parkinsonism

  • Symptoms of dementia? If so, consider evaluating for Parkinson disease, Lewy body dementia, vascular dementia, and frontotemporal dementia
  • Idiopathic: Note that up to a third of new-onset schizophrenic patients who have never been medicated may present with parkinsonian signs.

Stop or reduce the dosage of causative medication.


Switch to an atypical antipsychotic.


Anti-parkinson medications: 

  • Amantadine, 
  • Antimuscarinic agents, 
  • Dopamine agonists,
  • Levodopa 

Prevention of EPS 

Does the patient have EPS risk factors such as:

  • Elderly females: Increased risk of drug-induced parkinsonism and tardive dyskinesia.
  • Young males: Increased risk of dystonias. 
  • Previous history of EPS. 

If so, consider pre-emptively doing the following:

  • Use the lowest possible dose of low-risk antipsychotic medication (e.g. quetiapine).
  • Treat for the shortest possible time. 

Preventive Guidance for EPS

Let the patient and family know that if the patient has an acute dystonic reaction, they can give themselves a dose of over-the-counter diphenhydramine (Benadryl) until they see a health professional. 

EPS in Children/Youth 

Is the patient on a first-generation antipsychotic?

  • If so, consider stopping the first-generation antipsychotic, given that there is a higher risk with first-generation antipsychotics. 

Are there multiple antipsychotics?

  • If so, consider reducing the number of antipsychotics.

Is the lowest possible dosage of the SGA being used? 

  • Consider lowering the dosage if possible. 

Is quetiapine or clozapine being used? 

  • If not, consider switching to quetiapine or clozapine as they have a lower risk of EPS.

Has the patient been seen by neurology?

  • If not, consider referral to a neurologist. 

Are there still issues with EPS despite the above being tried, AND is antipsychotic treatment absolutely required? If so, then consider adding:  

  • Anticholinergic (Arana, 1988), 
  • Propranolol (Pringsheim, 2011)
  • Clonazepam (Pringsheim, 2011)
  • Mirtazapine for akathisia (Pringsheim, 2011)

Case, Part 2

D. is a 20-yo male in your practice. He was recently admitted to hospital for a brief psychotic episode and while in hospital was started on risperidone. He was discharged and is seeing you in follow-up. While his psychosis symptoms have improved and he is functioning much better, he is brought in for a same-day visit by his parents. He complains of neck stiffness and troubles moving his eyes...


What do you do?


You give him over-the-counter diphenhydramine (Benadryl), and symptoms improve within about 15-minutes. You ask him to stop his antipsychotic medications. You contact his treating psychiatrist to arrange rapid follow-up.


Arana G, Goff D, Baldessarini R, Keepers G. Efficacy of anticholinergic prophylaxis for neuroleptic induced acute dystonia. Am J Psychiatry 1988;145:993-6.


Divac N et al.: Review Article: Second-Generation Antipsychotics and Extrapyramidal Adverse Effects, BioMed Research International 2014,


Rummel-Kluge  C et al.: Second-Generation Antipsychotic Drugs and Extrapyramidal Side Effects: A Systematic Review and Meta-analysis of Head-to-Head Comparisons. Schizophr Bull. 2012 Jan; 38(1): 167–177. Published online 2010 May 31. doi: 10.1093/schbul/sbq042


D’Souza R, Hooten W: Extrapyramidal Symptoms (EPS), 2019. StatPearls [Internet]


Gharabawi GM, Bossie CA, Lasser RA, Turkoz I, Rodriguez S, Chouinard G. Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS): Cross-scale comparison in assessing tardive dyskinesia. Schizophr Res 2005;77:119-28.


Muench J, Hamer A.: Adverse Effects of Antipsychotic Medications, Am Fam Physician. 2010 Mar 1; 81(5): 617-622.


Shin HW, Chung SJ. Drug-induced parkinsonism. J Clin Neurol. 2012 Mar;8(1):15-21.

Clinical Guidelines

T Pringsheim, A Doja, S Belanger, S Patten; The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group. Treatment recommendations for extrapyramidal side effects associated with second-generation antipsychotic use in children and youth. Paediatr Child Health 2011;16(9):590-598.

About this Article

Written by the professionals at CHEO and the Royal Ottawa Mental Health Centre. 

Affichée le : Sep 27, 2019
Date de la dernière modification : Jan 12, 2024

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