June 2009
Reviewer: Jeff C. Huffman, MD
Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: case reports and a review of the literature
Seitz DP, Gill SS
Psychosomatics 2009; 50(1):8-15
Background: NMS is a known adverse event associated with the use of antipsychotics, and antipsychotics are the pharmacologic treatment of choice for delirium/agitation in medical-surgical patients. However, there has been little investigation of NMS when antipsychotics are used for the treatment of delirium/agitation; this is important because it can be an adverse effect of the delirium treatment and because it is a potential etiology of worsening delirium.
Methods: The authors present two cases of NMS associated with use of antipsychotics in patients with delirium, and performed a search of electronic databases (e.g. Medline) and a textbook for additional reports of NMS associated with treatment of delirium and agitation.
Results: The authors identified an additional 23 cases of NMS that occurred during the treatment of delirium/agitation among medically-ill patients. Haloperidol was used (alone or in combination with other agents) in 20 of these 23 cases; atypical antipsychotics were used in only approximately 10% of cases and in only one case did NMS occur with atypical antipsychotic monotherapy. Medication doses were highly variable (and not reported in all cases), but in more than half of cases when doses were reported, dosing exceeded recommended doses in published delirium guidelines. Classic symptoms of NMS (fever, muscle rigidity, abnormal vital signs/autonomic hyperactivity, elevated CPK, and elevated WBC) were seen in most cases, and patients recovered from the episodes with supportive care or specific treatments (bromocriptine used in ~50% of cases, dantrolene in 40%).
Discussion: It is clear that NMS can occur with the use of antipsychotics, including when they are used for treatment of delirium. The number of reported cases was to me somewhat surprising; on review of the cases themselves, most NMS cases occurred when haloperidol was given IM/PO (a route associated with much higher rates of EPS and probably higher rates of NMS) and seemingly less likely to occur when haloperidol was administered IV, a route many of us favor for its rapid impact and relative lack of motor side effects. NMS occurred at higher doses of antipsychotics, consistent with the NMS literature, and seemed to resolve with usual treatments. This review of case reports has the limitations of the case reports themselves, and true prevalence rates cannot be ascertained. Furthermore, NMS with atypical antipsychotics may be more common than this review indicates, since NMS with second-generation antipsychotics can have atypical features (often with fewer motor symptoms) and thus may be less dramatic or more easily overlooked.
In any event, this article is a good reminder that, when using antipsychotics to treat delirium/agitation in medically-ill patients, NMS is a rare but possible adverse effect and may be the cause of a worsening confusional state. One should remain aware of this potential effect, especially in patients getting high doses of typical antipsychotics (e.g., haloperidol) by the intramuscular or oral route, though NMS can occur with intravenous haloperidol or atypical antipsychotics.