Neuroleptic Malignant Syndrome
This patient has neuroleptic malignant syndrome (NMS), a potentially fatal complication of antipsychotic therapy that presents with the classic tetrad of hyperthermia, muscle rigidity, altered mental status, and autonomic instability—all of which are present in this case. 1
Clinical Reasoning
This 42-year-old man on risperidone 4 mg BID presents with the pathognomonic features of NMS:
- Hyperthermia: Temperature of 102.5°F meets the diagnostic criterion for NMS 1
- Muscle rigidity: Symmetric "lead pipe" rigidity of upper and lower extremities is characteristic of NMS, caused by dopamine D2 receptor blockade in nigrostriatal pathways 2, 1
- Altered mental status: Progressive lethargy to stupor with weak response to verbal stimuli 1
- Autonomic instability: Tachycardia (HR 120), hypertension (BP 170/105), diaphoresis, and labored respirations 2, 1
Why Not the Other Diagnoses?
Malignant hyperthermia is excluded because it requires exposure to inhalational anesthetics or succinylcholine, typically occurring within hours of exposure (not after ECT alone), and presents with rigor mortis-like rigidity rather than lead pipe rigidity 2
Meningitis would present with nuchal rigidity, headache, and photophobia rather than generalized symmetric extremity rigidity, and the clinical context of recent antipsychotic use makes NMS far more likely 2
Serotonin syndrome is less likely because: 2
- Onset is typically within minutes to hours (not progressive over an afternoon)
- Presents with hyperreflexia and clonus (this patient has decreased reflexes)
- Muscle tone is increased predominantly in lower extremities with hyperactive bowel sounds
- This patient lacks the characteristic mydriasis, sialorrhea, and diarrhea of serotonin syndrome
Critical Risk Factors Present
This patient has multiple high-risk features for NMS: 1
- Male gender (2:1 male predominance) 1
- Polypharmacy: Concurrent use of risperidone, benztropine, and hydroxyzine—coadministration of multiple psychotropic agents is present in >50% of NMS cases 1
- High-potency antipsychotic: Risperidone at 8 mg/day total dose
- Recent medication addition: Metoclopramide (Reglan), a dopamine antagonist, was just added and can precipitate or worsen NMS 2
Pathophysiology
NMS results from dopamine D2 receptor blockade in the CNS: 2
- Hypothalamic blockade produces increased temperature set point and loss of heat-dissipating mechanisms
- Nigrostriatal pathway blockade causes muscle rigidity and tremor
- Peripheral effects include increased calcium release from sarcoplasmic reticulum, leading to increased muscle contractility, rigidity, heat production, and rhabdomyolysis
Common Pitfall
The addition of metoclopramide (Reglan) for nausea is a critical error in this case—it is a dopamine antagonist that can precipitate or exacerbate NMS in patients already on antipsychotics. 2 The temporal relationship between Reglan administration and symptom onset (progressive lethargy throughout the afternoon after morning administration) strongly supports this as the precipitating factor.
Immediate Management Required
All antipsychotic medications and dopamine antagonists must be discontinued immediately—this is the single most critical intervention. 1, 3
The FDA label for risperidone explicitly warns that NMS can cause a "potentially fatal symptom complex" and requires immediate discontinuation of antipsychotic drugs. 3
Aggressive supportive care includes: 1
- Benzodiazepines for agitation and muscle activity
- External cooling measures for hyperthermia
- IV fluids for dehydration and to prevent renal failure from potential rhabdomyolysis
- Intensive monitoring in an ICU setting
With prompt recognition and management, mortality has decreased from 76% in the 1960s to <10-15% currently, with symptoms typically resolving within days to weeks after discontinuation of the offending agent. 1