88 case reports indicate newer antipsychotics may cause atypical presentations.

Fahd A. Zarrouf, MD 
Medicine/psychiatry resident 
Veena Bhanot, MD 
Associate professor, Psychiatry program 

West Virginia University, Charleston

When second-generation antipsychotics (SGAs) were introduced, clinicians hoped the drugs would not have the potential to cause neuroleptic malignant syndrome (NMS).1 Since then, however, case reports have made it clear that SGAs—like first-generation antipsychotics (FGAs)—can precipitate this life-threatening neurologic emergency.

To help you protect your patients receiving SGAs, this article explains how to:
• identify those at risk
•  recognize the different NMS presentations associated with each SGA
• continue antipsychotic treatment for a patient with a history of NMS.

CASE STUDY: A drug-induced disorder
Mrs. Z, age 39, has a history of multiple hospitalizations for schizoaffective disorder complicated by poor compliance and a history of benzodiazepine abuse. This time she was admitted with increased auditory hallucinations and paranoid delusions of her family trying to poison her. Despite multiple haloperidol injections (5 mg IM q4h prn), Mrs. Z continued to have hallucinations and remained agitated.

Haloperidol was discontinued and ziprasidone (20 mg IM q4h prn) was started. After 3 days, Mrs. Z became less agitated and had fewer hallucinations. The IM route was discontinued and oral ziprasidone was started at 40 mg bid, then titrated to 80 mg bid after 2 days. On the third day after titration, Mrs. Z fell twice. She hit her head in one fall, but a brain CT to rule out bleeding was normal.

The next day, Mrs. Z became more confused and developed fever, tremor, urinary incontinence, and a severe headache. She became obtunded, was intubated, and was transferred to the intensive care unit of a tertiary care center.

On admission, her temperature was 103° F (39.4° C); she had severe muscle rigidity and blood pressure of 85/60 mm Hg. Creatine phosphokinase (CPK) was 2,559 U/L (normal 24 to 170 U/L). Liver enzymes were elevated: alanine transaminase was 202 U/L (normal 13 to 50 U/L), and aspartate transaminase (AST) was 190 U/L (normal 15 to 46 U/L). At 140 μg/dL, Mrs. Z’s serum iron was within normal limits (40 to 150 μg/dL).

NEUROLEPTIC MALIGNANT SYNDROME
Clinical manifestations of NMS range from typical—as defined by the DSM-IV-TR
(Table 1)2,3—to atypical, without:
•  fever4
• rigidity5
• CPK elevation.

Many conditions resemble NMS (Table 2). Because NMS can be fatal without emergent diagnosis and treatment, maintain a high index of suspicion for this condition whenever you prescribe antipsychotics.

Table 1
DSM-IV-TR definition of NMS*

Table 2
NMS differential diagnosis