‘Scared’ and short of breath
While being treated for paranoid schizophrenia, Mr. C, age 42, suddenly develops a fever, high blood pressure, and altered mental status. How would you manage him?
Early the next morning, his blood pressure is 182/89 mm Hg, respirations are 30 to 40 breaths per minute, and heart rate is 120 beats per minute. He then receives IV lorazepam, 2 mg, after which his tachypnea, tachycardia, and elevated blood pressure improve.
The authors’ observations
A case-control study by Keck et al12 comparing 18 patients with NMS and 36 matched neuroleptic-treated patients with no history of the syndrome identified greater psychomotor agitation, significantly higher doses of neuroleptics, greater rates of dosage increase, and a greater number of IM injections as potential risk factors. Other potential risk factors include use of restraints, pre-existing CNS dopamine activity or receptor function abnormalities, and iron deficiency.2 Agitation, dehydration, and exhaustion were found to be the most consistent systemic factors predisposing patients taking antipsychotics to NMS in small case-control studies.13,14 Well-supported risk factors also include use of high-potency antipsychotics, prior episodes of NMS, age <40, male sex, malnutrition, organic brain syndromes, and lithium use.3,5,15
There is no way to predict the risk of NMS for an individual patient. Usually, symptoms develop within 4 weeks of starting an antipsychotic, but can occur after taking the same dose for many months. The onset may be within hours, but on average it is 4 to 14 days after initiating therapy. Among patients who develop NMS, 90% do so within 10 days.3,5
Mr. C’s risk factors include high-potency antipsychotic use, male sex, relatively high dose (haloperidol, 30 to 35 mg/d), agitation, dehydration, and exhaustion.
Managing NMS
The standard approaches for managing patients with NMS include discontinuing suspected triggering drugs and providing supportive care. Beyond supportive care, oral or IV benzodiazepines may relieve symptoms and speed recovery.2 Dopaminergic drugs, such as bromocriptine or amantadine, used alone or with other treatments, can reduce parkinsonism and disease duration and mortality.2 Dantrolene may be useful only for NMS patients who exhibit extreme temperature elevations, rigidity, and true hypermetabolism.16 Electroconvulsive therapy may be effective for NMS patients whose symptoms do not respond to supportive care and drug therapy or those with residual catatonic or parkinsonian symptoms.2
OUTCOME: Improvement, discharge
Mr. C is admitted to the hospital with the diagnosis of NMS and transferred to the intensive care unit (ICU) for treatment. After Mr. C is admitted to the ICU, apart from continuing the medication given in the ED, he also receives dantrolene, 2 mg/kg, then 1 mg/kg, 4 times a day, as well as IV lorazepam, 1 mg every 6 hours. His other medications include IV pantoprazole, 40 mg/d, for prophylaxis of stress ulcer. Diphenhydramine administration is changed to as needed. On the second day in the ICU, he has only mild upper extremity rigidity but no lower extremity rigidity. However, he suffers 1 seizure, which is treated with IV fosphenytoin at the loading dose, 18 mg/kg, then a maintaining dose of 5 mg phenytoin equivalent/kg/d.
Figure 3: Mr. C’s creatine kinase level (IU/L) during the first 5 days in the intensive care unit
Figure 4: Mr. C’s blood pressure before and after admission
Figure 5: Mr. C’s temperature before and after admissionMr. C remains in the ICU for 7 days. There he receives valproic acid, titrated to 500 mg in the morning and 1,000 mg at bedtime, for agitation. He also receives olanzapine, 5 mg/d, for psychotic symptoms. He develops deep vein thrombosis in the right cephalic vein, which is treated with subcutaneous enoxaparin, 1 mg/kg, and warfarin, 5 mg/d.
He is discharged from the hospital after 2 weeks and returns to the psychiatric facility. He continues to be treated for paranoid schizophrenia with olanzapine, 5 mg/d.
The authors’ observations
High-potency, typical antipsychotics can cause NMS, as shown in Mr. C’s case. It also can be caused by typical low-potency antipsychotics,3 atypical antipsychotics,17 antiemetic drugs,18 and lithium,19,20 and can occur after the withdrawal of levodopa and similar dopaminergic agents during Parkinson’s disease treatment.21 Atypical antipsychotics reported to be associated with NMS include clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, and paliperidone.22-27 Atypical antipsychotic-induced NMS also has been reported in children and adolescents.22,28-30
