Clozapine appears to cause NMS, although the presentation may be different than that of traditional antipsychotics. Levenson's original and Addonizio's modified criteria were more likely to diagnose NMS than were other criteria. Clozapine-associated NMS may present with fewer clinical features. Limitations are the lack of detailed information provided by many of the case reports and the use of "modified" diagnostic criteria for retrospective diagnosis.

We wish to com ment upon the case of neu ro lep tic ma lig nant syn drome (NMS) as so ci ated with queti apine that was reported in the Oc to ber is sue of the Journal (1). The author re ported queti apine use that was fol lowed by 13 days of restless ness, agi ta tion, and dia pho re sis. Loxap ine was then added to the regi men, and the next day the pa tient de vel oped the full ful mi nant syn drome of NMS, meet ing the cri te ria of Leven son (2), Addon izio and oth ers (3), DSM-IV (4), Caroff and oth ers (5), and, proba bly, Pope and oth ers (6). There have been sev eral cases of NMS as so ci ated with the use of atypi cal neu ro lep tics, par ticu larly clozap ine (7). It is strik ing how of ten the pres en ta tion is less ful mi nant with atypical neu ro lep tic use; ex tra py ra mi dal symp toms (EPS), in par ticu lar, are less promi nent. This is not sur pris ing, consid er ing the side-effects pro file of the atypi cals, which show fewer EPS than do clas sic agents.Given the above, we won der whether the author might com ment on the pos si bil ity of loxap ine be ing also a sig nifi cant contrib ut ing cause of the NMS. Loxap ine is a clas sic neu ro lep tic that has been as soci ated with NMS of the more ful mi nant va ri ety (8)-more like the case described by Al-Waneen (1), with prominent EPS and very high cre atine ki nase (CK). We be lieve that, with con comi tant use of loxap ine, it is in cor rect to conclude that queti apine in duced NMS in this case. It is also worth not ing that NMS de vel oped in spite of the use of loraze pam which Fink (9) rec om mends as a treat ment for NMS. Neuroleptic Malignant Syndrome Associated With Quetiapine: A Response Dear Edi tor:In their re view of 32 case re ports of neuro lep tic ma lig nant syn drome (NMS) related to clo zap ine or risperi done, Hasan and Buck ley (1) iden ti fied 20 of those cases as be ing NMS, ap ply ing DSM-IV cri te ria. The clini cal pic ture of NMS in those pa tients re sem bled that usu ally attrib ut able to con ven tional an tipsy chotics. They found that no suf fi cient evi dence ex ists cur rently to sup port the con cept of "atypi cal" NMS with novel an tipsy chot ics.With re gard to the case of Mr D that I described in my origi nal let ter (2), I would like to high light a few points. First, the pa ti ent's pro gres sive symp toms of restless ness, agi ta tion, trem ors, pro fuse sweat ing, and al tered men tal state (the pa tient was alert but ap peared dazed and dis or gan ized in his speech) be gan to develop 13 days into the queti apine trial at a dos age level of 250 mg twice daily. Those fea tures that were ret ro spec tively viewed as early mani fes ta tions of NMS pre ceded the use of loxap ine and lo razepam (taken as needed a few times over the next sev eral hours), dur ing which time the full syn dro mal pic ture evolved. Those 2 agents were ad min is tered to address the mis tak enly di ag nosed increased psy cho sis. Vi tal signs were not checked at the time. Of note, the pa tient re ceived no de pot medi ca tion...

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