Sue Henderson

EPSE & NMS Sue Henderson

Sue Henderson

Well, I did warn you about the

side effects

Those tablets you gave me are great but they’re making me walk

like a crab

Sue Henderson

Low potency V High potency

• Low potency Chlorpromazine (Largactil) 100mg is equivalent to 2mg of Haloperidol (serenace) a high potency anti-psychotic.

• High potency: high rates of Extra Pyramidal Side Effects (EPSE)

• Low potency: high rates of anti-cholinergic side effects

Sue Henderson

Low Potency V High PotencyHigh Anti-cholinergic & Sedative effects

High EPSE

Haloperidol 2 mg

Chlorpromazine

100 mg

Sue Henderson

Extra pyramidal side effects (EPSE)

• Acute dystonias: Oculogyric crisis, Torticollis, Lock jaw, Laryngeal spasm, Opisthotonos

• Akathisia• Parkinsonism (Rigidity,

bradykinesia, tremor)• Tardive dyskinesia

Sue Henderson

Dystonia: Oculogyric Crisis

• Muscles that control eyes movements spasm.

• Eyes roll up & person is unable to look downward.

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Oculogryric Crisis

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Dystonia: Torticollis

• Spasm of neck muscles.

• Neck is flexed backwards or to the side.

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Dystonia: Lock jaw (Trismus)

• Spasm of jaw muscle, also often involves the muscles of the tongue and floor of the mouth.

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Dystonia: Opisthotonos

• Spasm of paravertebral muscles with arching of back.

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Dystonia: Laryngeal spasm• Rare but potentially

fatal reaction causing difficulty with breathing. High risk: Young males on high potency antipsychotic with no anti-parkinson drug.

Sue Henderson

Treatment Laryngeal spasm

• Emergency.

• Stat parenteral benztropine (cogentin).

• Maintain airway

• Prevention: Concurrent antiparkinson or diazepam for young males on high potency antipsychotics

Sue Henderson

Akathisia (Most common EPSE)

• Restlessness, an irresistible urge to move (unable to sit still, pacing) and a feeling of “nervous energy”.

• Often mistaken for agitation. Worsened by additional antipsychotic dosage.

• Common cause of non compliance.

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Parkinsonism

• Muscle stiffness, rigidity, (cogwheel & lead pipe) shuffling gait, tremor, pill rolling, loss of facial expression, slowed movement (bradykinesia), reduced arm swing, absent movement (akinesia), drooling, stooped posture, tremor of lips (rabbit syndrome).

Sue Henderson

Pyramid shapeDrug induced

Parkinsonism

(reversible)

Dopamine & acetylcholine in balance = normal function

Dopamine blockade, upsets balance = tremor, rigidity, akinesia

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Tardive Dyskinesia• Serious, potentially irreversible, effect of

prolonged antipsychotics. Abnormal, involuntary movements of the face, eyes, mouth, tongue, trunk, limbs.

• Most common: twisting, protruding, darting tongue movements.

• Chewing & sideways jaw movements.

• Facial grimacing.

Sue Henderson

Sue Henderson

Neuroleptic Malignant Syndrome (NMS)

• Rare but potentially fatal• Muscular rigidity (may be localised to

head & neck), incontinence, confusion or delirium, excessive variation in BP& P & high Temp.

• Presentation highly variable: hours after 1st dose to unexpected appearance after months of uneventful treatment.

Sue Henderson

Treatment NMS

• Early detection vital to recovery• Stop anti-psychotic• Hydration• Transfer to ICU• Bromocriptine 5-10 mg tds but if no

response• Dantrolene

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Side Effect Drugs

Sue Henderson

S/E Drugs: Classification1. Antiparkinson: Benztropine (Cogentin),

benzhexol, biperiden, orphenadrine

2. Other drugs used to treat EPSE’s

3. Benzodiazepines.

4. Dopamine agonist: Bromocriptive (NMS)

5. Beta blocker: Propanolol (Inderal) & Clonidine (Catapres, Dixarit)

Sue Henderson

Indication

• Reduce EPSE of antipsychotics

Sue Henderson

Side Effect Drugs: Action

<

=

>

=

ACh

ACh

ACh

ACh

DA

DA

DA

DA

Excess levels of dopamine (positive schizophrenia)

Dopamine blocking antipsychotic drugs decrease effect of dopamine

Sometimes antipsychotic drugs block too much dopamine creating a pseudo-parkinsonism

Antiparkinson block ACh restoring a relative balance.

Sue Henderson

S/E Drugs Prescription

Routine prescription not advised because:

• Not all people develop EPSE’s

• Decrease effect of antipsychotics.

• Risk of worsening Tardive Dyskinesia.

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Side effect drugs cont…

• EPSE drugs have side effects also.

• Potential for abuse.

• Severity of EPSE’s fluctuate

• Exception: Young males on high potency antipsychotic (high risk of EPSE)

Sue Henderson

Antiparkinson SE (anticholinergic)• Common: dry mouth, dilated pupils, urinary

hesitancy, constipation & G.I. Upset, nausea, blurred vision.

• Less common: tachycardia, dizziness, hallucinations, euphoria, excitement, delirium, hyperpyrexia.

• Mneumonic for anticholinergic (O/D)

• Dry as a bone, red as a beet, blind as a bat, hot as a furnace, mad as a hatter.

Sue Henderson

EPSE risk factor tool

Patient factors:• Age > 40• Sex: Females,

males > 30 years• History ECT,

previous EPSE• Cognitive or

mood disorder

Treatment factors:• High/moderate

potency• Prolonged exposure• Depot injections• 2 or more

antipsychotics• No prophylactic

antiparkinson

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Antiparkinson effectiveness for EPSE

Good response: 1. Parkinsonism2. DystoniasPoor Response• AkathisiaMade Worse:• Tardive dyskinesia

Sue Henderson

Summary EPSE management

DISCONTINUEAFTER 2/52

BENZTROPINE(Cogentin)

DYSTONIA90% occur in1st 4.5 days

CHANGE TOATYPICAL ANTIPSYCHOTIC

BENZTROPINE(Cogentin)

REDUCEANTI-PSYCHOTIC

PARKINSONISM90% occur in1st 72 days

BENZTROPINE(Cogentin)

CHANGE TO ATYPICALANTIPSYCHOTIC

BENZODIAZEPINE(Valium )

BETA BLOCKER(Propranalol)

REDUCEANTI-PSYCHOTIC

AKATHISIA90% occur in1st. 73 days

LOWEST POSSIBLEDOSE

CHANGE TOATYPICAL ANTIPSYCHOTIC

CEASE ANTI PSYCHOTICIF POSSIBLE

Regular AIMS assess.to detect early

TARDIVE DYSKINESIAoccurs in 3% onanti-psychotics

Sue Henderson

References

• Aronne, L. J. (2001). Epidemiology, morbidity, and treatment of overweight and obesity. Journal of Clinical Psychiatry, 62(Suppl 23), 13-22.

• Fortinash, K. M., & Holoday-Worret, P. A. (2000). Psychiatric mental health nursing ( 2nd ed.). St. Louis: Mosby.

• Galbraith, A., Bullock, S. & Manias, E. (2001). Fundamentals of pharmacology (3rd ed.). Melbourne: Prentice Hall.

Sue Henderson

References• Kapur, S., Zipursky, R., Jones, C., Remington, G., &

Houle, S. (2000). Relationship between dopamine D-2 occupancy, clinical response, and side effects: A double-blind PET study of first-episode schizophrenia. American Journal of Psychiatry, 157(4), 514-520.

• Kapur, S., Zipursky, R., Jones, C., Shammi, C. S., Remington, G., & Seeman, P. (2000). A positron emission tomography study of quetiapine in schizophrenia - A preliminary finding of an antipsychotic effect with only transiently high dopamine D-2 receptor occupancy. Archives of General Psychiatry, 57(6), 553-559.

Sue Henderson

References

• Lindenmayer, J. P. (2001). Hyperglycemia associated with the use of atypical antipsychotics. Journal of Clinical Psychiatry, 62 Suppl 23, 30-38.

• Melkersson, K. I., & Hulting, A. L. (2001). Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents. Outcomes Management, 154(2), 205-212.

Sue Henderson

References

• Therapeutic guidelines. (2000). Psychotropic version 4. Melbourne: Therapeutic Guidelines Limited. Call Number: 615.788 P974P2000

• Turrone, P., Kapur, S., Seeman, M. V., & Flint, A. J. (2002). Elevation of prolactin levels by atypical antipsychotics. American Journal of Psychiatry, 159(1), 133-135.

• Wirshing, D. A., Spellberg, B. J., Erhart, S. M., Marder, S. R., & Wirshing, W. C. (1998). Novel Antipsychotics and New Onset Diabetes. Biological Psychiatry, 44(8), 778-783.