What is the most likely cause of nausea and decreased reflexes in all extremities in a patient with schizophrenia on risperidone (Risperdal) and electroconvulsive therapy (ECT), considering options such as malignant hyperthermia, meningitis, neuroleptic malignant syndrome, or serotonin syndrome?

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Neuroleptic Malignant Syndrome (NMS)

The most likely diagnosis is neuroleptic malignant syndrome (NMS), given the patient is on risperidone, presenting with nausea and decreased reflexes in all extremities after multiple weeks of treatment. 1

Clinical Reasoning

Why NMS is the Primary Diagnosis

NMS is a potentially fatal syndrome caused by antipsychotic drugs like risperidone, characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (including nausea). 1 The key clinical features include:

  • Mental status changes - consistent with worsening psychosis mentioned 1
  • Autonomic dysfunction - manifesting as nausea 1
  • Neuromuscular abnormalities - decreased reflexes in all extremities represent the spectrum of muscle rigidity/hypertonicity 1
  • Temporal relationship - NMS most commonly occurs during the first weeks of treatment or after dose increases, fitting this 5-week hospitalization timeline 2

The pathophysiology involves dopamine D2 receptor blockade, which risperidone causes as a primary mechanism of action. 1, 3

Ruling Out Alternative Diagnoses

Malignant hyperthermia can be excluded because:

  • It occurs during anesthesia administration for ECT, not weeks later 4
  • It would present acutely during the ECT procedure itself 4

Meningitis is unlikely because:

  • The clinical presentation lacks the classic triad of fever, neck stiffness, and headache
  • Decreased reflexes globally would be atypical for meningitis
  • The temporal relationship to risperidone use is more consistent with NMS 2

Serotonin syndrome is less likely because:

  • The patient is not on serotonergic agents based on the clinical scenario
  • Serotonin syndrome typically presents with hyperreflexia and clonus, not decreased reflexes 3
  • Laboratory findings distinguish NMS (elevated CPK, LFTs, WBC with low serum iron) from serotonin syndrome 3

ECT Considerations

ECT itself can cause transient fever responses and nausea as common side effects, but these typically resolve within the day of treatment, not persist across multiple sessions. 4 The guidelines clearly state that nausea, vomiting, and muscle aches are minor side effects that "usually do not persist beyond the day of the treatment." 4

The combination of risperidone plus ECT does not exclude NMS - in fact, ECT has been used as a treatment for severe, persistent NMS cases. 5 The presence of ECT does not protect against NMS development from the antipsychotic medication. 5

Critical Diagnostic Features

The decreased reflexes in all extremities represent a variant presentation of NMS. While classic NMS presents with muscle rigidity, atypical presentations with minor muscular rigidity or altered tone patterns are well-documented. 2 One case report specifically describes NMS with "minor muscular rigidity" that made diagnosis difficult. 2

Long-acting risperidone formulations can complicate diagnosis because symptoms may persist or evolve over 7 weeks due to sustained drug release. 2 This extended timeline fits with the 5-week hospitalization period described.

Immediate Management Required

Discontinue risperidone immediately - this is the primary treatment for NMS. 1, 3

Provide intensive symptomatic treatment and medical monitoring, including:

  • Check CPK, liver function tests (LDH, AST), WBC count, and serum iron to confirm NMS 3
  • Monitor vital signs continuously 1
  • Treat autonomic instability supportively 1

Consider dantrolene - this is the most effective evidence-based drug treatment for NMS. 3

Obtain neurology consultation given the widespread decreased reflexes and need for comprehensive neurological assessment. 4

Common Pitfall

Do not assume ECT side effects explain persistent symptoms beyond the treatment day. 4 The guidelines are explicit that minor ECT side effects like nausea resolve within 24 hours of treatment. 4 Persistent symptoms across multiple weeks point to a separate process like NMS rather than ECT complications.

References

Research

Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management.

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2012

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Electroconvulsive Therapy for Neuroleptic Malignant Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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