Extreme Elevation of Creatinine Phosphokinase Levels in Neuroleptic Malignant Syndrome Associated With Atypical Antipsychotics

To the Editor: Neuroleptic malignant syndrome may develop subsequent to treatment with typical or atypical antipsychotics (1) . An elevated level of creatinine phosphokinase is not required for a DSM-IV diagnosis of neuroleptic malignant syndrome, but it is common. During the past 5 years, creatinine phosphokinase has typically been reported at levels between 1,000 U/l and 10,000 U/l in cases of neuroleptic malignant syndrome (2, 3) . A creatinine phosphokinase level of 800,000 U/l was reported for a patient who was being treated with a conventional antipsychotic (3) . We report a case involving the use of the atypical antipsychotic clozapine and a creatinine phosphokinase level that exceeded 390,000 U/l.

In our patient, clozapine may not have been the sole cause of neuroleptic malignant syndrome, since risperidone (2) and aripiprazole (2), despite their discontinuance, may have contributed. In addition, the concomitant use of valproate (4) and lithium (1) has been reported as a risk factor.

Some authors have noted that patients being treated with atypical antipsychotics may present with atypical features of neuroleptic malignant syndrome (1, 2) . Other investigators have reported typical neuroleptic malignant syndrome features from treatment with atypical antipsychotics (4) . Although our patient presented with neck stiffness, no rigidity was found, and no fever was initially noted. Additionally, he did not manifest a number of symptoms associated with neuroleptic malignant syndrome, such as altered mental status, tremor, diaphoresis, mutism, incontinence, and sialorrhea.

Many patients who develop neuroleptic malignant syndrome with high creatinine phosphokinase levels develop renal failure, which is often a main cause of death. In the present case, despite extreme elevations of creatinine phosphokinase levels, renal function was preserved, although cardiac and pulmonary complications emerged. Nearly all reports of neuroleptic malignant syndrome within the past 5 years involved a creatinine phosphokinase level ≤10,000 U/l. Why do creatinine phosphokinase levels vary so markedly? Some investigators have suggested that the creatinine phosphokinase level is a prognostic indicator (3) . If this is the case, our patient’s total recovery is striking.