What are the potential interactions between Duloxetine (Cymbalta) and Hydroxyzine (Vistaril)?

Duloxetine and Hydroxyzine Interaction

Duloxetine and hydroxyzine can be used together with caution, but monitoring for increased sedation and potential QT interval prolongation is necessary, especially in patients with other risk factors for cardiac arrhythmias.

Pharmacological Properties and Mechanism of Interaction

• Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor (SNRI) used for generalized anxiety disorder, depression, and various pain conditions 1
• Hydroxyzine (Vistaril) is an antihistamine medication with anxiolytic properties 2
• No direct significant pharmacokinetic interaction between duloxetine and hydroxyzine has been documented in major guidelines 3
• Both medications can cause sedation as individual agents, with potential for additive sedative effects when combined 4, 2

Potential Risks and Concerns

• QT interval prolongation is a concern as hydroxyzine is listed among medications that can prolong QT interval 3
• Duloxetine is extensively metabolized by CYP1A2 and CYP2D6 enzymes, but hydroxyzine is not known to significantly inhibit these pathways 5, 6
• Combination may lead to increased risk of:
  • Sedation and drowsiness (additive effect) 4, 2
  • Potential anticholinergic effects, especially in older adults 3
  • Theoretical risk of QT interval prolongation, particularly if other QT-prolonging medications are used concurrently 3

Evidence on Combined Use

• A study in mice showed that combining duloxetine with hydroxyzine did not provide additional anxiolytic benefits compared to either medication alone 4
• The combination did not show synergistic effects on brain monoamine levels in animal models 4
• No major drug interaction warnings between these specific medications appear in recent clinical practice guidelines 3

Recommendations for Clinical Practice

• Assess for other medications that might interact with either drug:

  • Avoid adding other QT-prolonging medications to this combination 3
  • Be cautious with other CNS depressants that could increase sedation 3, 2

• Monitor patients for:

  • Excessive sedation or drowsiness, especially during initial combination therapy 4, 2
  • Signs of cognitive impairment, particularly in older adults 3
  • Cardiovascular effects in patients with pre-existing cardiac conditions 3

• Consider dose adjustments:

  • Start with lower doses of both medications when using in combination 4
  • Adjust based on patient response and tolerability 1, 2

Special Populations and Considerations

• Older adults (>65 years):

  • Use with extra caution due to increased sensitivity to sedative and anticholinergic effects 3
  • Tricyclic antidepressants are potentially inappropriate for older adults due to anticholinergic effects, making duloxetine a potentially better choice in this population 3

• Patients with cardiac conditions:

  • Exercise caution in patients with pre-existing QT prolongation or those taking other medications that affect cardiac conduction 3
  • Consider ECG monitoring in high-risk patients 3

Clinical Decision Algorithm

1. Assess necessity of combination therapy (consider if monotherapy with either agent would be sufficient)
2. Screen for contraindications:
   • History of QT prolongation
   • Concurrent use of other QT-prolonging medications
   • Severe hepatic or renal impairment
3. If no contraindications exist, consider starting with lower doses of both medications
4. Monitor for sedation, cognitive effects, and cardiovascular parameters
5. Titrate doses based on efficacy and tolerability

While this combination can be used with appropriate monitoring, clinicians should remain vigilant for potential additive sedative effects and cardiac concerns, especially in vulnerable populations 3, 4, 2.