INTERACTION BETWEEN FLUOXETINE AND HALOPERIDOL - PHARMACOKINETIC AND CLINICAL IMPLICATIONS

The extent and clinical significance of the pharmacokinetic interactio n between fluoxetine and haloperidol was studied in 13 schizophrenic p atients with prominent negative symptoms. Patients stabilized on chron ic low-dose haloperidol (3-8 mg day(-1)) received additional fluoxetin e (20 mg day(-1)) for 12 consecutive weeks. Mean plasma concentrations of haloperidol increased significantly from 6.5+/-2.4 nmol l(-1) at b aseline to 8.8+/-3.6 nmol l(-1) (P< 0.01) at week 12 of fluoxetine tre atment, but this effect was not associated with an increase in mean ex trapyramidal side effects score on the Simpson and Angus Scale, The im provement in negative symptomatology, as measured by the Scale for Ass essment of Negative Symptoms, did not correlate significantly with the increase in plasma haloperidol levels. Though our findings confirm th at fluoxetine impairs haloperidol clearance, this interaction is unlik ely to have adverse clinical consequences, at least in patients chroni cally stabilized on a low dosage of haloperidol. As fluoxetine is a po tent inhibitor of cytochrome P450 (CYP) 2D6, these results also provid e indirect evidence for an involvement of CYP2D6 in the metabolism of haloperidol. (C) 1997 The Italian Pharmacological Society.