Antipsychotics The Essentials Module 4 Adverse Effects Neuroleptic

Outline • Neuroleptic Malignant syndrome – Epidemiology – Associated drugs – Risk Factors –

“ NMS is an acute disorder of thermoregulation and neuromotor control carrying a mortality

NMS - Epidemiology • Estimates of incidence were once around 3% • Recent statistics

Dopamine antagonists NMS - Associated Drugs Antipsychotics Antiemetics FGA SGA High potency Low potency

NMS - Risk Factors • Dehydration is present in about 92 % of patients

NMS - Clinical Manifestations Hyperthermia Rigidity • Higher than 38°C, even higher than 40°C

Lab Testing - Serum CK: - More than 1, 000 UI (has high as

NMS - Pathophysiology • Unknown • Dopamine antagonism might be involved Hypothalamus Nigrostriatal pathway:

NMS – Differential Diagnosis Related Disorders Serotonin Syndrome Unrelated Disorders Heatstroke Malignant Catatonia CNS

Management of NMS • General – Stop causative agent – Supportive care • Specific

Key Points • NMS is a potentially life-threatening complication of antipsychotic drug use. •

References and Further Reading • Janicak, P G. , Marder S R. , and.

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Antipsychotics: The Essentials Module 4: Adverse Effects Neuroleptic Malignant Syndrome Flavio Guzmán, MD

Outline • Neuroleptic Malignant syndrome – Epidemiology – Associated drugs – Risk Factors – Clinical Manifestations – Pathophysiology – Differential Diagnosis – Management

“ NMS is an acute disorder of thermoregulation and neuromotor control carrying a mortality rate of about 21% when untreated” Janicak, P G. , Marder S R. , and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5 th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

NMS - Epidemiology • Estimates of incidence were once around 3% • Recent statistics suggest incidence of 0. 01 0. 02% • The syndrome has been described in all age groups (most are young adults) Strawn JR, Keck PE, Jr. , Caroff SN. Neuroleptic malignant syndrome. The American Journal of Psychiatry 2007; 164: 870 -6.

Dopamine antagonists NMS - Associated Drugs Antipsychotics Antiemetics FGA SGA High potency Low potency E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com

NMS - Risk Factors • Dehydration is present in about 92 % of patients ( risk factor or early complication? ) • Concomitant lithium use • Use of high potency agents • Long-acting injections • High antipsychotic dose (not dose dependent) E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com

NMS - Clinical Manifestations Hyperthermia Rigidity • Higher than 38°C, even higher than 40°C • Typical: “lead pipe rigidity” NMS Mental Status Changes Autonomic Instability • Agitated delirium with confusion • Tachycardia, tachypnea, labile or high BP E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com

Lab Testing - Serum CK: - More than 1, 000 UI (has high as 100, 000 UI) - Not specific for NMS - Degree of elevation correlates w/ disease severity and prognosis - Other abnormalities - Leukocytosis - Electrolyte abnormalities E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com

NMS - Pathophysiology • Unknown • Dopamine antagonism might be involved Hypothalamus Nigrostriatal pathway: Rigidity Hypothalamus: Hyperthermia Frontal lobe / Mesocortical blockade : altered mental status Strawn JR, Keck PE, Jr. , Caroff SN. Neuroleptic malignant syndrome. The American Journal of Psychiatry 2007; 164: 870 -6.

NMS – Differential Diagnosis Related Disorders Serotonin Syndrome Unrelated Disorders Heatstroke Malignant Catatonia CNS infections (Viral Encephalitis) E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com

Management of NMS • General – Stop causative agent – Supportive care • Specific agents (limited evidence) – Dantrolene – Bromocriptine – Amantadine • ECT Strawn JR, Keck PE, Jr. , Caroff SN. Neuroleptic malignant syndrome. The American Journal of Psychiatry 2007; 164: 870 -6.

Key Points • NMS is a potentially life-threatening complication of antipsychotic drug use. • Treatment with high potency FGAs at high doses increases risk. • Clinical manifestations include: mental status changes, rigidity, hyperthermia and autonomic instability. • Serum CK levels greater than 1000 IU/L are suggestive of NMS. • If NMS is suspected, antipsychotics should be discontinued immediately.

References and Further Reading • Janicak, P G. , Marder S R. , and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5 th ed. Philadelphia: Lippincott Williams & Wilkins, 2010. • Strawn JR, Keck PE, Jr. , Caroff SN. Neuroleptic malignant syndrome. The American Journal of Psychiatry 2007; 164: 870 -6. • E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed. ), Up. To. Date. http: //uptodate. com