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

2. Outline Neuroleptic Malignant syndrome Epidemiology Associated drugs
Risk Factors
Clinical Manifestations
Pathophysiology
Differential Diagnosis
Management

3. “ 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.
5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

4. NMS - Epidemiology Estimates of incidence were once around 3%
Recent statistics suggest incidence of %
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.

5. NMS - Associated Drugs Dopamine antagonists Antipsychotics FGA
High potency
Low potency
SGA
Antiemetics
E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed.), UpToDate.

6. 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.), UpToDate.

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

8. 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.), UpToDate.

9. 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.

10. NMS – Differential Diagnosis
Related Disorders
Serotonin Syndrome
Malignant Catatonia
Unrelated Disorders
Heatstroke
CNS infections (Viral Encephalitis)
E Wijdicks (2011). Neuroleptic Malignant Syndrome In: Michael J Aminoff. (Ed.), UpToDate.

11. Management of NMS General Specific agents (limited evidence) ECT
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.

12. 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.

13. References and Further Reading
Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th 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.), UpToDate.