Is hydroxyzine (an antihistamine) effective for treating chronic nausea and vomiting?

Hydroxyzine for Chronic Nausea and Vomiting

Hydroxyzine is not recommended as a first-line treatment for chronic nausea and vomiting, but may be considered as an adjunctive antihistamine therapy in specific situations when other more established antiemetics have failed. 1, 2

Evidence-Based Treatment Algorithm for Chronic Nausea and Vomiting

First-Line Treatments:

• Dopamine receptor antagonists should be initiated first:
  • Haloperidol
  • Metoclopramide
  • Prochlorperazine 2

Second-Line Options (if first-line fails):

1. Add a 5-HT3 antagonist (e.g., ondansetron)
2. Add an anticholinergic agent (e.g., scopolamine)
3. Add an antihistamine:
   • Meclizine (preferred)
   • Hydroxyzine (alternative) 2, 1

Third-Line Options:

• Add corticosteroids (e.g., dexamethasone)
• Consider continuous IV/SC infusion of antiemetics 2

Hydroxyzine's Role and Evidence

Hydroxyzine has demonstrated antiemetic effects in laboratory testing as noted in the FDA label 1, but clinical evidence for its effectiveness in chronic nausea and vomiting is limited. The FDA label states that "antiemetic effect, both by the apomorphine test and the veriloid test, has been demonstrated," but this does not translate to strong clinical evidence for chronic nausea and vomiting management.

The NCCN Palliative Care guidelines (2009) mention antihistamines (including hydroxyzine) as a potential add-on therapy for persistent nausea and vomiting, but only after first trying dopamine receptor antagonists and 5-HT3 antagonists 2.

A recent study (2024) showed that hydroxyzine may be effective for postoperative nausea and vomiting prevention 3, but this evidence is:

• Limited to the postoperative setting
• Based on a retrospective study rather than a randomized controlled trial
• Not specific to chronic nausea and vomiting

Special Considerations

Opioid-Induced Nausea and Vomiting

If nausea and vomiting are opioid-related:

• Metoclopramide is recommended as first-line therapy
• Hydroxyzine or diphenhydramine may be considered for pruritus management, which could indirectly help with nausea 2

Advantages of Hydroxyzine

• Mild sedative properties may be beneficial for patients with anxiety-related nausea
• May help with pruritus if present alongside nausea
• Generally affordable and accessible

Disadvantages and Cautions

• Sedation may be problematic for some patients
• Not as well-studied for chronic nausea as other antiemetics
• May cause anticholinergic side effects (dry mouth, constipation, urinary retention)
• Limited evidence for efficacy in chronic nausea and vomiting

Monitoring and Follow-up

When using hydroxyzine or any antiemetic for chronic nausea and vomiting:

• Assess response within 48 hours to determine effectiveness
• Monitor for sedation, which is common with hydroxyzine
• Consider adding alternative therapies if nausea persists
• Evaluate for underlying causes of chronic nausea that may require specific treatment 2, 4

Conclusion

While hydroxyzine has some antiemetic properties, the evidence supports using dopamine receptor antagonists as first-line therapy for chronic nausea and vomiting, with hydroxyzine potentially serving as an adjunctive therapy in specific cases. The limited evidence for hydroxyzine's effectiveness in chronic nausea and vomiting suggests it should not be used as monotherapy but may be considered as part of a stepwise approach when other options have failed.