Neuroleptic Malignant Syndrome (NMS) is rare and serious medical condition characterized by the sudden onset of fever, and muscle rigidity in a patient on anti-psychotic medication with two or more of the following: tremor, sweating, difficulty swallowing, incontinence, confusion, not speaking (mutism), rapid pulse, elevated or fluctuating blood pressure (including low blood pressure), increased white blood cells (leukocytosis), and high creatinine kinase (CPK -- a muscle enzyme, signifying a breakdown of muscle cells).  There may also be additional signs of autonomic instability such as salivation, and fluctuating pupil diameter.  Rapid breathing, high serum creatinine, and low blood pressure are sometimes present.  Renal failure has been reported in 57 cases (Ren Fail. 2002 Jul;24(4):539-43).  Although the CPK elevation may only be minor, minor elevations are common in many mental disorders and are also caused by injections, vigorous exercise, and a variety of other factors. Two-thirds of cases start within the first week of starting an anti-psychotic.

The syndrome is caused by anti-psychotic medications (also called neuroleptics) and, if it occurs, it most likely occurs after a sudden increase in medication or during dehydration.  It has been reported after a lithium overdose (Pharmacotherapy. 2003 Jun;23(6):811-5), anti-depressant overdose, or, especially, provoked by the discontinuation of anti-parkinsonian medication in patients with Parkinson's Disease.

NMS is often treated by stopping the anti-psychotic medication, maintaining hydration with IV fluids, cooling the patient, giving amantidine, dantrolene and/or bromocriptine, and giving antibiotics if necessary.  It has been treated with ECT (Psychiatr Prax. 2003 Jul;30(5):279-82).  Patients without any specific medication or ECT treatment for NMS have twice the fatality rate in reported cases: 21% vs 10% (Convuls Ther. 1991;7(2):111-120).  The only controlled study I have found reported with adding pulsed steroids to dantrolene and bromocriptine was of considerable benefit.

NMS has been reported with both traditional and atypical anti-psychotics with case reports involving clozapine, risperidone, olanzapine (more than 50% of reported cases on atypcials), ziprasidone, amisulpride, and quetiapine.

Neuroleptic Malignant Syndrome Rare and Fatalities Very Rare: A study by McGill University of 4861 patients treated with anti-psychotics in hospital in Mexico found only 8 cases (0.165%).  Seven of the eight were being treated with haloperidol. There were no fatalities. Neuroleptic malignant syndrome in Mexico. Montoya A, Ocampo M, Torres-Ruiz A. Can J Clin Pharmacol. 2003 Fall;10(3):111-3

Neuroleptic Malignant Syndrome: A Dysregulated Sympathetic Nervous System Hyperactivity: D2 receptor antagonism may cause the hyperthermia of NMS by blocking heat-loss pathways in hypothalamus. Automonic dysfunction is a core component of NMS. Perif catecholamines are elevated. Catatonia, a harbinger of NMS, is a frontal lobe syndrome. AJP 2/99.

Stopping Meds at First Signs Reported to Help: A study of 657 patients who were watched for early signs of NMS and had it stopped immediately had a much lower rate of NMS (0.2% vs 2.1%) than 197 patients treated without the special precautions. All were treated with atypical anti-psychotics. Israel. Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients. Shiloh R, Valevski A, Bodinger L, Misgav S, Aizenberg D, Dorfman-Etrog P, Weizman A, Munitz H. Int Clin Psychopharmacol. 2003 May;18(3):147-9

Steroid Pulse Therapy Helps: In a DB PC study of 20 Parkinson's patients with NMS, all patients received levodopa, dantrolene, and bromocriptine. The half given pulsed steroids recovered in an average of 7 days vs. 18 days for those on placebo. Japan. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson's disease. Sato Y, Asoh T, Metoki N, Satoh K. J Neurol Neurosurg Psychiatry. 2003 May;74(5):574-6