Clozapine to Olanzapine

To the Editor: The role of olanzapine in the treatment of severe refractory schizophrenia is unclear. We report our experience in switching five men with refractory schizophrenia and self-induced water intoxication from clozapine to olanzapine.

We stabilized five men with a regimen of clozapine, but they were still too ill to be released from the hospital. We hoped they would have a better response to olanzapine. Their mean age was 40.8 years. Their mean current hospital stay was 13.6 years. The patients were all on a specialized ward for the treatment of self-induced water intoxication. All patients initially had a clozapine blood level greater than 360 ng/ml. One patient also received lithium, and another took valproic acid as an adjuvant to clozapine.

We increased their olanzapine dose and tapered their clozapine dose over a 3-week period. Their mean maximum olanzapine dose was 24 mg/day (range=20–25 mg/day). We obtained an olanzapine blood level on each patient to ensure compliance. We did not alter adjuvant medications. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) was completed by a psychologist before the start of olanzapine and again after 4 months of treatment or at discontinuation, if this occurred earlier.

We had to discontinue olanzapine in two patients after 2 months when they developed rage attacks. We took two other patients off of olanzapine after 4 months when their psychotic symptoms markedly increased. We left one patient taking olanzapine, because clinically he was unchanged from when he was taking clozapine. The mean PANSS score for the five patients increased from 91.4 to 125.8 (paired t test=2.74, df=4, p=0.05).

The fluid consumption of the five patients, as assessed by weight monitoring, did not increase significantly with olanzapine treatment. As a consequence, the clinical deterioration of the four patients resulted directly from an exacerbation of their schizophrenia rather than through a worsening of their self-induced water intoxication.

On the basis of this open-label study of refractory schizophrenic patients with self-induced water intoxication who were only partially responsive to clozapine, switching from clozapine to olanzapine may not be helpful.