From the FDA Drug Label
Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine.
The effect of Fluoxetine on serum levels of Haloperidol is an increase in blood levels. This is due to a possible pharmacodynamic and/or pharmacokinetic interaction between Fluoxetine and Haloperidol.
- Key points:
- Elevation of blood levels of Haloperidol has been observed in patients receiving concomitant Fluoxetine.
- This interaction may require caution and dose adjustment when coadministering Fluoxetine and Haloperidol 1.
From the Research
Fluoxetine can significantly increase serum levels of haloperidol by approximately 20-35% when co-administered, and clinicians should consider reducing the haloperidol dose by about 25-30% and monitor patients closely for increased side effects. This interaction occurs because fluoxetine is a potent inhibitor of the CYP2D6 enzyme, which is primarily responsible for haloperidol metabolism 2. When prescribing these medications together, clinicians should consider the following key points:
- Monitor patients closely for increased side effects such as extrapyramidal symptoms, sedation, QTc prolongation, and anticholinergic effects.
- Baseline ECG monitoring is advisable before starting this combination, with follow-up ECGs if symptoms develop.
- Blood level monitoring of haloperidol may be helpful when available.
- The interaction typically begins within 1-2 weeks of starting fluoxetine but can persist for weeks after fluoxetine discontinuation due to its long half-life and active metabolites. Alternative SSRIs with less CYP2D6 inhibition (such as sertraline, citalopram, or escitalopram) should be considered if a patient requires both an antipsychotic and antidepressant medication 3. It is also important to note that the study by 4 found a significant increase in haloperidol concentrations (more than 100 per cent) two weeks after the addition of fluoxetine, which suggests a pharmacokinetic interaction between the two medications. However, the most recent and highest quality study on this topic is 2, which provides the most reliable evidence for the interaction between fluoxetine and haloperidol. In terms of patient management, the following steps can be taken:
- Start with a low dose of haloperidol and gradually increase as needed and tolerated.
- Monitor patients closely for signs of increased haloperidol levels, such as extrapyramidal symptoms or sedation.
- Consider using alternative antipsychotics or antidepressants with less potential for interaction.
- Educate patients about the potential risks and benefits of combining fluoxetine and haloperidol, and inform them of the importance of regular monitoring and follow-up.