What is the recommended treatment for anxiety using antihistamines, such as hydroxyzine (Selective Histamine H1 Receptor Antagonist) or diphenhydramine (Diphenhydramine Hydrochloride)?

Treatment of Anxiety with Antihistamines

Antihistamines are not recommended as first-line treatment for anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) being the preferred pharmacological options. 1, 2

Role of Antihistamines in Anxiety Treatment

Hydroxyzine (Vistaril)

• FDA-approved for "symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested" 3
• Can be used as an adjunctive treatment rather than monotherapy
• Effectiveness for long-term anxiety management (beyond 4 months) has not been established by systematic clinical studies 3
• Potential benefits:
  • Rapid onset compared to SSRIs/SNRIs
  • Non-addictive alternative to benzodiazepines
  • May be particularly helpful when anxiety is accompanied by insomnia or pruritus 3

Diphenhydramine (Benadryl)

• Not FDA-approved specifically for anxiety
• First-generation antihistamines like diphenhydramine should be used cautiously due to sedative effects 4
• May be useful for nighttime symptoms but not recommended for daytime anxiety management

Evidence for Antihistamine Use in Anxiety

Hydroxyzine has shown some efficacy for generalized anxiety disorder (GAD):

• More effective than placebo in controlled trials 5
• Comparable efficacy to benzodiazepines and buspirone in limited studies 5
• However, evidence quality is low with high risk of bias in available studies 5

Treatment Algorithm for Anxiety

1. First-line treatments (strongest evidence):

   • SSRIs (e.g., sertraline)
   • SNRIs (e.g., venlafaxine extended release)
   • Cognitive behavioral therapy (CBT) 1, 2

2. Second-line treatments:

   • Hydroxyzine may be considered when:
     • First-line treatments are ineffective or contraindicated
     • Rapid symptom relief is needed
     • Patient has comorbid insomnia or pruritus
     • Benzodiazepines are contraindicated

3. Dosing considerations for hydroxyzine:

   • Start at lower doses in elderly patients
   • Use caution in patients with risk factors for QT prolongation
   • Monitor for sedation and cognitive impairment 3

Important Precautions with Antihistamines

• Sedation risk: Hydroxyzine and diphenhydramine cause drowsiness; patients should be warned about driving or operating machinery 3
• Potentiation of CNS depressants: Dose reduction of narcotics, non-narcotic analgesics, and barbiturates may be needed when used with hydroxyzine 3
• QT prolongation: Hydroxyzine should be used with caution in patients with risk factors for QT prolongation or congenital long QT syndrome 3
• Elderly patients: Start with lower doses due to increased risk of confusion and oversedation 3

Monitoring and Follow-up

• Assess response within 1-2 weeks of initiating therapy
• Monitor for side effects, particularly sedation and cognitive impairment
• Reassess periodically for continued usefulness of the medication 3
• Consider transitioning to first-line treatments for long-term management

Conclusion

While hydroxyzine has some evidence supporting its use in anxiety disorders, it should generally be considered as an adjunctive or alternative treatment when first-line options (SSRIs, SNRIs, CBT) are not suitable. The sedative properties of antihistamines may be beneficial for short-term management of anxiety with insomnia, but their cognitive side effects and limited evidence for long-term efficacy make them suboptimal for primary treatment of anxiety disorders.