Fluvoxamine dose-dependent interaction with haloperidol and the effects on negative symptoms in schizophrenia

Augmentation with low-dose fluvoxamine (50-100 mg/day) to antipsychotic treatment may improve the negative symptoms in schizophrenic patients, but involves a risk of drug-drug interaction. We studied the effects of fluvoxamine on plasma concentrations of haloperidol and reduced haloperidol, and their clinical symptoms, in haloperidol treated patients. Twelve schizophrenic inpatients with prevailingly negative symptoms receiving haloperidol 6 mg/day were additionally treated with incremental doses of fluvoxamine for 6 weeks (25, 75 and 150 mg/day for 2 weeks each). Plasma drug concentrations were monitored together with clinical assessments before and after each phase of the three fluvoxamine doses. Geometric mean of haloperidol concentrations during coadministration of fluvoxamine 25, 75 and 150 mg/day were 120% (95%CI; 114-127%), 139% (95%CI; 130-149%), and 160% (95%CI; 142-178%) of those before fluvoxamine coadministration, respectively. We found positive correlations between increase in plasma haloperidol concentrations and plasma fluvoxamine concentrations. Scores in negative symptoms were significantly reduced after fluvoxamine coadministration, whereas no changes were observed in the other psychiatric symptoms or any subgrouped side effects. Therefore, this study indicates that fluvoxamine increases plasma haloperidol concentrations in a dose-dependent manner. However, relatively small elevations in haloperidol concentration did not lead to the development of extrapyramidal symptoms under the conditions of this study.