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Olanzapine: interaction study with imipramine

J T Callaghan1, B J Cerimele, K J Kassahun

  • 1Lilly Laboratory for Clinical Research, Wishard Memorial Hospital, Indianapolis, IN 46202, USA.

Journal of Clinical Pharmacology
|March 20, 1998
PubMed
Summary
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This study found that olanzapine, an atypical antipsychotic, is safe for use with imipramine in depressed patients. While olanzapine caused mild sedation and reduced motor speed, it did not significantly alter imipramine pharmacokinetics or show a metabolic drug interaction.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Clinical Trials

Background:

  • Psychotic depression often requires combined antipsychotic and antidepressant treatment.
  • Olanzapine is an atypical antipsychotic with broad receptor affinity.
  • Imipramine pharmacokinetics can indicate hepatic enzyme activity (CYP2D6, CYP1A2, CYP3A).

Purpose of the Study:

  • To evaluate the safety and pharmacokinetics of olanzapine and imipramine when used alone and in combination.
  • To determine the potential for drug interactions between olanzapine and imipramine.

Main Methods:

  • An open-label, three-way randomized crossover study involving nine healthy male participants.
  • Administration of olanzapine (5 mg) and imipramine (75 mg) individually and concurrently.

Related Experiment Videos

  • Measurement of psychomotor performance, plasma drug concentrations, and clinical laboratory tests.

    • Main Results:

    • Olanzapine was safe, with transient sedation and postural hypotension observed.
    • Olanzapine slightly decreased motor-speed performance, but effects were marginally significant.
    • Olanzapine did not alter imipramine or desipramine pharmacokinetics, indicating no significant metabolic interaction via CYP2D6.

    Conclusions:

    • Olanzapine can be safely coadministered with imipramine in patients with psychotic depression.
    • The combination does not appear to pose a significant metabolic drug interaction risk.
    • Further research may explore long-term effects and broader patient populations.