OLANZAPINE - INTERACTION STUDY WITH IMIPRAMINE

Olanzapine is an ''atypical'' antipsychotic agent with a high affinity for serotonin 5HT(2A/C), 5HT(3), 5HT(6), and dopamine D-1, D-2, D-3, D-4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant me dications. Imipramine pharmacokinetics serve as a marker for hepatic C YP2D6, CYP1A2, CYP3A activity. An open-label, three-way randomized cro ssover study was done to determine the safety, pharmacokinetics, and p otential for a drug interaction between olanzapine (5 mg) and imiprami ne (75 mg). Each drug was administered alone and in combination. Nine healthy men, ages 32 to 54 years, enrolled in the study. Psychomotor p erformance capacities, plasma olanzapine, imipramine, desipramine conc entrations, and clinical laboratory tests were measured. Pharmacokinet ic variables, vital signs, subjective tests for liveliness, and psycho motor outcomes were analyzed using a two-way ANOVA. Olanzapine was saf e. Sedation, postural hypotension, and minor vital sign alterations oc curred during all treatments. On the liveliness questionnaire, patient s generally reported poorer (less lively) scores with olanzapine alone or coadministered with imipramine versus baseline scores. These effec ts disappeared within 24 hours after administration. Olanzapine alone and in combination decreased motor-speed tasks (finger tapping and vis ual-arm random reach) compared with baseline or imipramine treatment. Peak 6-hour changes were statistically significant but clinical import ance was only marginal. Olanzapine concentrations were <19% greater th an with imipramine. But olanzapine did not affect the kinetics of imip ramine or desipramine and, therefore, did not show a metabolic drug in teraction involving CYP2D6.