What is the next step in management for a patient with schizophrenia and depression, currently on risperidone (Risperdal) and fluoxetine (Prozac), who develops hyperthermia, hypertension, tachycardia, and muscle rigidity after promethazine (Phenergan) is discontinued?

Management of Neuroleptic Malignant Syndrome

The next step in management is to discontinue risperidone (option D), as it is the antipsychotic medication most likely responsible for triggering neuroleptic malignant syndrome (NMS) in this patient.

Clinical Presentation Analysis

This 43-year-old man with schizophrenia and depression is presenting with classic signs of NMS:

• Hyperthermia (39.5°C)
• Altered mental status (encephalopathy)
• Muscle rigidity
• Autonomic instability (hypertension, tachycardia, tachypnea, diaphoresis)

These findings strongly suggest NMS, which is a potentially life-threatening condition associated with antipsychotic medications like risperidone 1.

Etiology and Pathophysiology

NMS is primarily caused by dopamine receptor blockade from antipsychotic medications. In this case:

• Risperidone is a potent dopamine antagonist and the most likely culprit 2
• The combination of risperidone with other psychotropic medications (fluoxetine and promethazine) increases the risk 1
• Promethazine has already been discontinued, which was appropriate as it can also contribute to NMS 3

Management Algorithm

1. Discontinue the offending antipsychotic agent (risperidone) 4

   • This is the most critical first step in management
   • Continuing risperidone would perpetuate the syndrome and increase mortality risk

2. Provide supportive care:

   • IV fluid administration for dehydration
   • External cooling for hyperthermia
   • Cardiac monitoring
   • Respiratory support if needed

3. Consider pharmacological interventions only after discontinuing the antipsychotic:

   • Dantrolene (option A) may be considered for severe rigidity and hyperthermia, but only after discontinuing the antipsychotic 4
   • Cyproheptadine (option B) is primarily indicated for serotonin syndrome, not NMS 4

4. Address the fluoxetine consideration:

   • While fluoxetine (option C) could potentially contribute to serotonin effects, the clinical presentation is more consistent with NMS than serotonin syndrome
   • Discontinuing fluoxetine would be a secondary consideration after addressing the primary cause (risperidone)

Evidence-Based Rationale

The American Academy of Pediatrics and other guidelines emphasize that the management of NMS should include "immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy" 4, 3.

Mortality from NMS has decreased from 76% in the 1960s to <10-15% more recently, largely due to early recognition and prompt discontinuation of the offending agent 1.

Important Considerations

• NMS can occur with both typical and atypical antipsychotics, including risperidone 2
• The combination of multiple psychotropic agents increases the risk of NMS 1
• Even though promethazine has been discontinued, the patient's symptoms have progressed, indicating that risperidone is likely the primary trigger

Common Pitfalls to Avoid

• Delaying discontinuation of the antipsychotic medication
• Focusing on pharmacological treatments before removing the causative agent
• Confusing NMS with serotonin syndrome (which would warrant cyproheptadine)
• Attributing symptoms solely to promethazine when multiple agents may be contributing

After discontinuing risperidone, the patient will require close monitoring and supportive care. Once the patient has recovered, careful consideration should be given to future antipsychotic therapy, as there is a risk of recurrence if reintroduced too quickly 5.