Effect of fluoxetine added to haloperidol in treatment-resistant schizophrenic patients

To assess the effect of fluoxetine added to haloperidol, we measured repeatedly the changes of plasma haloperidol concentrations and clinical effects in 8 treatment-resistant schizophrenic patients who taking haloperidol. Fluoxetine 20mg/day was added for the first one month, and dose was increased up to 60mg/day with a month interval according to clinical responses of each subject. The scores of PANSS and its sub-scales tend to be lowered after adding fluoxetine without respect to the dose, though the differences were not significant statistically. Three of 8 patients showed 30% or more decrease in positive symptom subscale and/or general psychopathology subscale of PANSS after adding fluoxetine 40mg or higher dose. Parkinsonian symptoms were newly developed or aggravated in two patients at 40mg and four at 60mg dose of fluoxetine. Plasma haloperidol levels did not show any change after adding fluoxetine, even in patient who showed clinical responses. Reduced haloperidol concentrations increased up to 250% of baseline level(mean: 2.67 ng/ml/10mg dose) according to the increase of plasma concentration of fluoxetine and norfluoxetine. These results suggest that fluoxetine added to haloperidol can produce therapeutic effect and/or side effect in some treatment-resistant schizophrenic patients, and these effects seem to be not related to the plasma haloperidol level.