Virtually all neuroleptics are capable of inducing the syndrome, including the newer atypical antipsychotics. The standard of care for the recognition of neuroleptic malignant syndrome has shifted considerably over the past 15 years. Neuroleptic malignant syndrome belongs in the differential diagnosis of any patient receiving a neuroleptic who develops a high fever or severe rigidity. In addition to measurement of creatinine phosphokinase and white blood cell count, important tests to rule out other etiologies include urinalysis to measure electrolytes, including calcium and magnesium; kidney, liver, and thyroid function tests; lumbar puncture; an electroencephalogram; and a computed tomography or magnetic resonance imaging scan of the head. Although specific treatment remains controversial, supportive treatment such as antipyretics, a cooling blanket, and intravenous fluids to correct dehydration and electrolyte abnormalities is critical and widely supported by consensus. Most patients recover from neuroleptic malignant syndrome in two to 14 days without any cognitive impairment, and new dysfunction usually is attributable to very high fever, hypoxia, or other complications, rather than neuroleptic malignant syndrome per se.

The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

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