What is the interaction between Hydroxyzine and Fluoxetine?

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Last updated: March 3, 2025View editorial policy

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From the Guidelines

Hydroxyzine and fluoxetine can be used together, but caution is advised due to the potential risk of serotonin syndrome, a potentially life-threatening condition caused by elevated brain serotonin levels, as noted in the 2020 clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.

Key Considerations

  • When combining hydroxyzine and fluoxetine, patients should be closely monitored for signs of serotonin syndrome, which can include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity.
  • The risk of serotonin syndrome is higher when serotonergic medications are combined, and symptoms can arise within 24 to 48 hours after combining medications.
  • Treatment of serotonin syndrome requires hospitalization, discontinuation of all serotonergic agents, and supportive care with continuous cardiac monitoring.

Potential Side Effects

  • Increased sedation and anticholinergic effects are possible when taking hydroxyzine and fluoxetine together.
  • Both medications can cause QT interval prolongation, so caution is warranted in patients with heart conditions or those taking other QT-prolonging medications.
  • Common side effects may include increased drowsiness, dry mouth, constipation, and blurred vision.

Recommendations

  • Patients should avoid alcohol and be cautious when driving or operating machinery until they know how this combination affects them.
  • If excessive sedation occurs, hydroxyzine could be taken at bedtime rather than during the day.
  • Close monitoring by a healthcare provider is essential when combining hydroxyzine and fluoxetine to minimize the risk of adverse effects and ensure safe use.

From the Research

Interaction between Hydroxyzine and Fluoxetine

  • The interaction between hydroxyzine and fluoxetine is not directly addressed in most of the provided studies 2, 3, 4, 5.
  • However, one study suggests that anxiolytic drugs such as hydroxyzine might be better in coadministration with antidepressants, particularly with specific serotonin reuptake inhibitors like fluoxetine 6.
  • This study found that the reversal of helpless behavior by fluvoxamine or fluoxetine was not modified by daily coadministration of hydroxyzine, suggesting a potential beneficial interaction between hydroxyzine and fluoxetine 6.
  • It is essential to note that fluoxetine can raise serum levels of other medications, and caution is advised when prescribing low doses of other medications, such as hydroxyzine, and monitoring serum levels closely 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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