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?
Coordination
- Movements slowed?
- Trouble with rapid alternating movements?
- Slow to stand from a seated position?
Gait
- Shuffling gait?
- Postural instability?
Mental Status Examination (MSE)
|
General |
Alert and oriented with EPS Changes in level of consciousness suggest other causes, e.g. neuroleptic malignant syndrome Normal attention, memory, executive function |
|
Affect |
Decreased facial expression or a ‘mask-like facies? |
|
Speech |
Slow to move or speak? (bradykinesia) Dysarthria or dysphonia? |
Vitals
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).
Investigations
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 |
Symptoms |
Management / Treatment |
|
Acute dystonia |
Sustained abnormal postures and muscle spasms, especially of the head or neck Examples
DDx muscle rigidity / tension
|
Stop antipsychotic
Anticholinergic medications such as
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?
Is an antipsychotic absolutely required?
|
|
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):
|
|
Akathisia |
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
|
Stop or reduce the dosage of causative antipsychotic
Beta-adrenergic blockers (such as propranolol (Inderal) at 20-80 mg / day).
Benzodiazepines
Amantadine
Clonidine
Mirtazapine
Mianserin
Cyproheptadine
Propoxyphene
|
Late EPS
- Occurs after chronic, long-term or prolonged treatment (after several months).
- Serious negative impact on quality of life.
|
Type of Later EPS |
Symptoms |
Treatment |
|
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
|
Stop the offending agent Switching to one with a lower risk
|
|
Neuroleptic-induced parkinsonism |
Tremor, skeletal muscle rigidity, bradykinesia
DDx parkinsonism
|
Stop or reduce the dosage of causative medication.
Switch to an atypical antipsychotic.
Anti-parkinson medications:
|
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.
Reference
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,
http://dx.doi.org/10.1155/2014/656370
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]
https://www.ncbi.nlm.nih.gov/books/NBK534115/
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.
https://www.aafp.org/afp/2010/0301/p617.html
Shin HW, Chung SJ. Drug-induced parkinsonism. J Clin Neurol. 2012 Mar;8(1):15-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325428/
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223903/
About this Article
Written by the professionals at CHEO and the Royal Ottawa Mental Health Centre.
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