Neuroleptic malignant syndrome: Don’t let your guard down yet
88 case reports indicate newer antipsychotics may cause atypical presentations.
Ziprasidone. Administering IM ziprasidone or combining any form of the drug with other psychotropics increases NMS risk. Although most cases featured typical presentations, 1 case reported absence of muscle rigidity, which is present in >90% of patients with NMS associated with FGAs.
NMS sequelae related to SGAs
Brain injury following NMS can cause truncal ataxia, limb ataxia, athetosis, hemiballismus, dysmetria, dysarthria, sensory function problems, balance problems, persistent amnesia, difficulties comprehending commands, attention problems, and electroencephalograph or MRI abnormalities.23,24 Postmortem studies of patients with NMS have revealed cerebellar degeneration, reduction of Purkinje and granule cells, and gliosis in the dentate nucleus.25,26
Why some patients develop sequelae after NMS while others recover is unknown. Sustained hyperpyrexia, preexisting medical or neurologic disorders, polypharmacy, prolonged courses, and delayed diagnosis may play a role.25-27
CASE CONTINUED: A complicated illness
Mrs. Z was diagnosed with NMS. Ziprasidone was discontinued, and supportive treatment, bromocriptine (2.5 mg po qid), and lorazepam (2 mg IV qid) were started. Temperatures of 101° to 103° F (38.3° to 39.4° C) persisted for the next 2 days. This hyperthermia was difficult to control because of suspected meningitis.
The team started ceftriaxone (2 gm IV q12h) while awaiting lumbar puncture results. CSF showed mild white blood cell elevation of 20/cu mm (normal 0 to 5/cu mm) with 62% neutrophils (normal 0 to 6%), normal protein, normal glucose, and negative cultures. After 2 days of antibiotic therapy, the patient developed diarrhea and was diagnosed with Clostridium difficile-associated colitis, a side effect of the antibiotic.
Treatment is mainly supportive
Recognizing NMS signs is the first and most important step to quick diagnosis and early medical intervention. Recommendations for medical treatment of NMS vary widely, but most stress stopping the triggering drug and initiating supportive care (Table 3).27-29
Several medications have been used off-label to treat NMS based on anecdotal clinical reports. Benzodiazepines such as parenteral lorazepam, 1 to 2 mg every 6 to 8 hours, have been used to treat catatonic symptoms.30 Dopamine agonists—including bromocriptine, 2.5 mg every 8 hours—have reduced the duration and mortality of NMS but have the potential to worsen psychotic symptoms and cause hypotension and emesis.30
Table 3
Treating NMS: Where to start
| Stop offending agent(s) |
Provide intensive hemodynamic and supportive care:
|
CASE CONTINUED: Resuming antipsychotic Tx
Five days after intubation, Mrs. Z started to improve and was extubated successfully. However, she developed severe truncal ataxia, upper extremity tremors (resting and intentional), athetosis, hemiballismus, dysmetria, and dystonia. She continued to experience hallucinations after transfer back to the psychiatric floor.
Oral olanzapine challenge was started at 2.5 mg/d and titrated up to 10 mg/d over the next 7 days. Her psychotic symptoms showed mild improvement but her ataxic movements worsened and she fell frequently. Benztropine, 1 mg po bid, was added to her regimen and helped with the tremor. She was transferred for rehabilitation and eventually discharged home.
If a patient needs antipsychotics
If a patient who has experienced NMS continues to need pharmacotherapy for psychosis, wait 1 or 2 weeks after NMS symptoms resolve before restarting any antipsychotic.31 Although most patients can be treated safely with an antipsychotic after having NMS, clearly document the indications and your discussions with the patients and their families.
No conclusive evidence indicates which antipsychotic might lower a patient’s risk of recurrent NMS. Using an FGA in patients who recover from NMS carries a 30% risk of recurrent episodes.3 Data on the recurrence of NMS with SGAs are inconclusive. No relationship was found between relapse rate and patients’ age or sex.32
Regardless of which drug you choose, start with a low dosage and titrate slowly. You also can protect patients by reducing risk factors for NMS, such as dehydration, and considering alternate therapies such as electroconvulsive therapy, when appropriate.
This paper was among those entered in the 2007 Promising New Investigators competition sponsored by the Neuroleptic Malignant Syndrome Information Service (NMSIS). The theme of this year’s competition was “New insights on psychotropic drug safety and side effects.”
Current Psychiatry is honored to publish this peer-reviewed, evidenced-based article on a clinically important topic for practicing psychiatrists.
NMSIS is dedicated to reducing morbidity and mortality of NMS by improving medical and psychiatric care of patients with heat-related disorders; providing support information for medical professionals, patients, and families; and improving scientific understanding of these conditions through research.
