What medications can cause Neuroleptic Malignant Syndrome (NMS)?

From the Guidelines

Neuroleptic Malignant Syndrome (NMS) is primarily caused by antipsychotic medications, especially first-generation (typical) antipsychotics like haloperidol, fluphenazine, chlorpromazine, and thioridazine, as well as second-generation (atypical) antipsychotics such as risperidone, olanzapine, quetiapine, and aripiprazole, with the latter generally having lower rates of NMS. Other medications that can trigger NMS include those that affect dopamine transmission, such as metoclopramide, prochlorperazine, promethazine, and certain antiemetics 1. Additionally, abrupt withdrawal of dopaminergic medications used for Parkinson's disease, like levodopa and carbidopa, can precipitate a similar syndrome.

Key Medications Associated with NMS

• First-generation antipsychotics: haloperidol, fluphenazine, chlorpromazine, and thioridazine
• Second-generation antipsychotics: risperidone, olanzapine, quetiapine, and aripiprazole
• Dopamine-affecting medications: metoclopramide, prochlorperazine, promethazine, and certain antiemetics
• Dopaminergic medications for Parkinson's disease: levodopa and carbidopa

Risk Factors and Prevention

Risk factors for NMS include rapid dose escalation, high-potency antipsychotics, parenteral administration, dehydration, and previous episodes of NMS 1. Clinicians should monitor patients starting these medications for early signs of NMS, including unexplained fever, muscle stiffness, and mental status changes, as prompt recognition and medication discontinuation are essential for management. The management of NMS involves primarily supportive care and removal of the initiating agent, with treatments such as IV fluids for dehydration, external cooling measures for fever, and benzodiazepines for agitation 1.

Clinical Considerations

Given the potential for NMS with antipsychotic medications, it is crucial to weigh the benefits and risks of these medications, especially in vulnerable populations such as young adults and those with a history of NMS. The coadministration of psychotropic agents seems to be an especially high risk factor for precipitating NMS, highlighting the need for careful consideration of medication regimens 1. By prioritizing the monitoring of patients on these medications and being aware of the signs and symptoms of NMS, clinicians can significantly reduce the morbidity and mortality associated with this condition.

From the FDA Drug Label

Antipsychotic drugs including RISPERIDONE can cause a potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS) NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including ZYPREXA

Medications that can cause Neuroleptic Malignant Syndrome (NMS) include:

• Risperidone 2
• Olanzapine (ZYPREXA) 3 These medications are antipsychotic drugs that can cause NMS, a potentially fatal symptom complex.

From the Research

Medications that can cause Neuroleptic Malignant Syndrome (NMS)

• Antipsychotic medications, most notably haloperidol 4
• Atypical antipsychotics, including:
  • Olanzapine 4, 5, 6, 7
  • Clozapine 5
  • Risperidone 5
  • Quetiapine 5
• Other drugs, such as:
  • L-dopa 8
  • Antidepressants 8
  • Antihistaminic agents 8

Characteristics of NMS

• Rare and potentially fatal complication 4, 6, 7
• Idiosyncratic side effect resulting from neuroleptic drugs 6
• Life-threatening condition with mortality risk 7
• Associated with dopamine receptor antagonism 8

Treatment of NMS

• Immediate withdrawal of all neuroleptics 4, 8
• Supportive care 4, 8
• Fever control 4
• Management of autonomic instability 4, 8
• Pharmacologic management with dantrolene and bromocriptine 4, 8