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Neuroleptic Malignant Syndrome Associated With Atypical Antipsychotics in Pediatric Patients: A Review of Published Cases

Paul E. Croarkin, D.O.; Graham J. Emslie, M.D.; and Taryn L. Mayes, M.S.

Objective: To retrospectively examine published cases of neuroleptic malignant syndrome (NMS) in patients aged 18 and below who had been treated with atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole).

Data Sources: Information was collected via MEDLINE searches in February 2006 and May 2007. The term neuroleptic malignant syndrome was used and cross-referenced with individual atypical antipsychotics. The authors also contacted (by telephone and in writing) pharmaceutical companies that produce and market atypical antipsychotics for any data on NMS.

Study Selection: Twenty case reports (written in English only and published from 1991-2007) were identified and reviewed. These publications all described symptoms of NMS in patients aged 18 or younger who had been treated with atypical antipsychotics.

Data Extraction: Data were reviewed and compared with 3 diagnostic criteria (DSM-IV-TR, Levenson's, and Caroff and Mann's) for NMS. Interventions and outcomes were also reviewed.

Data Synthesis: Twenty case reports were identified and presented with a descriptive approach. Sixteen cases met criteria for NMS, with at least 1 of the diagnostic sets utilized. The majority of cases involved male subjects. All patients recovered.

Conclusions: Young patients can develop NMS during treatment with atypical antipsychotics. Symptoms of this disorder are consistent with those described in adults. Although NMS is rare in this population, clinicians should maintain a high index of suspicion. Appropriate caution in treating children and adolescents with any antipsychotic is warranted.


(J Clin Psychiatry 2008;69:1157-1165. Online Ahead of Print June 17, 2008.)

Received Nov. 14, 2007; accepted Jan. 9, 2008. From the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.

Dr. Croarkin received second place in the 2006 Neuroleptic Malignant Syndrome Information Service (NMSIS) "Promising New Investigators Competition" for this manuscript. This involved a monetary award/partial travel costs for the 2006 annual meeting of the American Psychiatric Association.

This manuscript was presented as an abstract/poster during the 53rd annual meeting of the American Academy of Child and Adolescent Psychiatry, Oct. 24­29, 2006, San Diego, Calif.

Dr. Emslie has received research grants from Eli Lilly, Forest, Somerset, Shire, and Biobehavioral Diagnostics; is a consultant for Eli Lilly, GlaxoSmithKline, Wyeth-Ayerst, Shire, and Biobehavioral Diagnostics; and is on the speakers' bureau for McNeil Consumer and Specialty Pharmaceuticals. Dr. Croarkin and Ms. Mayes report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Paul Croarkin, D.O., Children's Medical Center Pediatric Psychiatry Outpatient Clinic, 6330 Harry Hines, Suite 1200, Dallas, TX 75235 (e-mail: