Which antipsychotics do not interact with tamoxifen (Nolvadex)?

Antipsychotics That Don't Interact with Tamoxifen

Aripiprazole, ziprasidone, and olanzapine are the preferred antipsychotics for patients taking tamoxifen as they have minimal to no interaction with the CYP2D6 enzyme system that metabolizes tamoxifen to its active form. 1

Understanding the Interaction Concern

Tamoxifen is metabolized by the CYP2D6 enzyme to its active metabolite endoxifen, which is responsible for its anticancer effects. Medications that inhibit CYP2D6 can reduce tamoxifen's efficacy and potentially increase the risk of breast cancer recurrence.

CYP2D6 Inhibition Classification of Antipsychotics

• Minimal/No CYP2D6 Inhibition (Preferred options):

  • Aripiprazole
  • Ziprasidone
  • Olanzapine
  • Lurasidone
  • Paliperidone

• Moderate CYP2D6 Inhibition (Use with caution):

  • Risperidone
  • Quetiapine (lower doses)

• Strong CYP2D6 Inhibition (Avoid):

  • Chlorpromazine
  • Haloperidol
  • Perphenazine
  • Thioridazine

Evidence-Based Recommendations

The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines emphasize careful selection of medications for patients taking tamoxifen, considering the potential impact of CYP2D6 inhibition on tamoxifen efficacy 1. While these guidelines focus primarily on antidepressants, the same pharmacological principles apply to antipsychotics.

Similar to antidepressants, where paroxetine and fluoxetine are strongly contraindicated due to their potent CYP2D6 inhibition 1, 2, certain antipsychotics should also be avoided based on their metabolic profiles.

Clinical Application

When selecting an antipsychotic for a patient on tamoxifen:

1. First-line options: Aripiprazole, ziprasidone, olanzapine

   • These have minimal interaction with CYP2D6 and are least likely to interfere with tamoxifen metabolism

2. Second-line options: Lurasidone, paliperidone

   • These also have favorable metabolic profiles regarding CYP2D6

3. Use with caution: Risperidone, quetiapine

   • Monitor for reduced tamoxifen efficacy if these must be used

4. Avoid: Chlorpromazine, haloperidol, perphenazine, thioridazine

   • These significantly inhibit CYP2D6 and may substantially reduce tamoxifen's effectiveness

Monitoring Recommendations

• Regular assessment of breast cancer treatment response is crucial when any antipsychotic is prescribed concurrently with tamoxifen
• Monitor for psychiatric symptom control and antipsychotic side effects
• Consider the overall medication regimen, as multiple medications with even mild CYP2D6 inhibition can have additive effects

Important Considerations

The American Society of Clinical Oncology specifically notes that CYP2D6 genetic testing is not recommended to guide therapy when prescribing tamoxifen 3. Instead, the focus should be on avoiding known strong CYP2D6 inhibitors whenever possible.

While most research has focused on antidepressant-tamoxifen interactions 1, 2, the same pharmacological principles apply to antipsychotics that inhibit CYP2D6, as both medication classes can potentially reduce the conversion of tamoxifen to its active metabolites.