Reinduction of neuroleptic malignant syndrome by lithium

The psychopharmacologic management of psychotic patients who have had neuroleptic malignant syndrome poses a dilemma for clinicians. Neuroleptic malignant syndrome can recur when neuroleptics are readministered, but there are equal numbers of reports of safe resumption of neuroleptic treatment in patients who have had the syndrome. In an effort to avoid reexposure to neuroleptics, the authors treated two bipolar patients who were clinically recovered from episodes of neuroleptic malignant syndrome with lithium alone. Both patients rapidly developed recurrent neuroleptic malignant syndrome after only 300 and 1,200 mg of lithium, respectively. Possible pathogenetic mechanisms are reviewed, although a definitive explanation for such a sudden and dramatic toxic effect is not available.