EPSE & NMS Sue Henderson Sue Henderson Those tablets you gave me are great but they’re making me walk like a crab Sue Henderson Well, I did warn you about the side effects 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 anticholinergic side effects Sue Henderson Low Potency V High Potency High Anti-cholinergic & Sedative effects Chlorpromazine 100 mg Haloperidol 2 mg High EPSE Sue Henderson Extra pyramidal side effects (EPSE) 1. Acute dystonias: Oculogyric crisis, Torticollis, Lock jaw, Laryngeal spasm, Opisthotonos 2. Akathisia 3. Parkinsonism (Rigidity, bradykinesia, tremor) 4. Tardive dyskinesia Sue Henderson Dystonia: Oculogyric Crisis • Muscles that control eyes movements spasm. • Eyes roll up & person is unable to look downward. Sue Henderson Oculogryric Crisis Sue Henderson Dystonia: Torticollis • Spasm of neck muscles. • Neck is flexed backwards or to the side. Sue Henderson Dystonia: Lock jaw (Trismus) • Spasm of jaw muscle, also often involves the muscles of the tongue and floor of the mouth. Sue Henderson Dystonia: Opisthotonos • Spasm of paravertebral muscles with arching of back. Sue Henderson 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. Sue Henderson 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 Drug induced Pyramid shape Parkinsonism (reversible) Dopamine & acetylcholine in balance = normal Sue Henderson function Dopamine blockade, upsets balance = tremor, rigidity, akinesia 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 Sue Henderson Side Effect Drugs Sue Henderson S/E Drugs: Classification • Antiparkinson: Benztropine (Cogentin), benzhexol, biperiden, orphenadrine • Other drugs used to treat EPSE’s 1. Benzodiazepines. 2. Dopamine agonist: Bromocriptive (NMS) 3. Beta blocker: Propanolol (Inderal) & Clonidine (Catapres, Dixarit) Sue Henderson Indication • Reduce EPSE of antipsychotics Sue Henderson Side Effect Drugs: Action ACh ACh < = DA Excess levels of dopamine (positive schizophrenia) DA Dopamine blocking antipsychotic drugs decrease effect of dopamine ACh > ACh = Sue Henderson DA DA Sometimes antipsychotic drugs block too much dopamine creating a pseudo-parkinsonism Antiparkinson block ACh restoring a relative balance. S/E Drugs Prescription Routine prescription not advised because: • Not all people develop EPSE’s • Decrease effect of antipsychotics. • Risk of worsening Tardive Dyskinesia. Sue Henderson 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 Sue Henderson Treatment factors: • High/moderate potency • Prolonged exposure • Depot injections • 2 or more antipsychotics • No prophylactic antiparkinson Antiparkinson effectiveness for EPSE Good response: 1. Parkinsonism 2. Dystonias Poor Response • Akathisia Made Worse: • Tardive dyskinesia Sue Henderson Summary EPSE management DYSTONIA 90% occur in 1st 4.5 days PARKINSONISM 90% occur in 1st 72 days AKATHISIA 90% occur in 1st. 73 days TARDIVE DYSKINESIA occurs in 3% on anti-psychotics BENZTROPINE (Cogentin) REDUCE ANTI-PSYCHOTIC REDUCE ANTI-PSYCHOTIC Regular AIMS assess. to detect early DISCONTINUE AFTER 2/52 BENZTROPINE (Cogentin) BETA BLOCKER (Propranalol) CEASE ANTI PSYCHOTIC IF POSSIBLE CHANGE TO ATYPICAL ANTIPSYCHOTIC BENZODIAZEPINE (Valium) CHANGE TO ATYPICAL ANTIPSYCHOTIC CHANGE TO ATYPICAL ANTIPSYCHOTIC LOWEST POSSIBLE DOSE BENZTROPINE (Cogentin) 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 D2 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. Sue Henderson