Is hydroxyzine (an antihistamine) effective for treating anxiety?

Hydroxyzine for Anxiety

Hydroxyzine is FDA-approved for symptomatic relief of anxiety and tension associated with psychoneurosis, though its effectiveness for long-term use (beyond 4 months) has not been systematically established. 1

Evidence for Efficacy

Hydroxyzine demonstrates anxiolytic efficacy in generalized anxiety disorder (GAD), with several key characteristics:

• Onset of action: Significant reduction in anxiety scores occurs within the first week of treatment at 50 mg/day, with superiority over placebo maintained throughout 4-week trials 2
• Mechanism: Acts as a sedative antihistamine (H1 receptor antagonist) with anxiolytic properties, approved for this use in both Europe and the United States 3
• Comparative effectiveness: Shows equivalent efficacy to benzodiazepines (chlordiazepoxide) and buspirone in head-to-head comparisons, though evidence quality is limited 4

Clinical Positioning

Hydroxyzine should be considered a second-line or adjunctive option rather than first-line treatment for anxiety disorders:

• First-line treatments for GAD remain SSRIs (escitalopram, sertraline, paroxetine) and SNRIs (venlafaxine, duloxetine) based on robust evidence and guideline recommendations 3
• Hydroxyzine is notably absent from major anxiety disorder treatment guidelines (NICE, S3, Canadian CPG, AACAP 2020) as a recommended agent 3
• The 2010 Cochrane review concluded that despite superiority over placebo, high risk of bias in studies and small sample sizes prevent recommending hydroxyzine as a reliable first-line treatment 4

Specific Clinical Scenarios Where Hydroxyzine May Be Useful

Procedural/situational anxiety in children:

• Approved and practical for anxiolysis during medical procedures (imaging, minor interventions) 3
• Available in tablets and syrup with few contraindications in pediatric populations 3

Acute agitation management:

• Used as chemical restraint in psychiatric settings for children and adolescents, though with important caveats 3
• Risk of paradoxical increase in rage exists, which cannot be predicted unless previously documented 3

Benzodiazepine withdrawal support:

• Hydroxyzine 25-50 mg can reduce withdrawal symptoms and anxiety during lorazepam discontinuation 5
• Particularly useful at 50 mg for patients with prominent withdrawal symptomatology 5

Dosing and Administration

• Standard anxiolytic dose: 50 mg/day for GAD 6, 2
• Pediatric procedural anxiety: Dosing varies; consult specific protocols 3
• Duration limitation: FDA label notes effectiveness beyond 4 months has not been systematically assessed 1

Adverse Effects and Precautions

Common side effects:

• Sleepiness/drowsiness (28% vs 14% placebo) - typically transient, appearing in first week and diminishing with continued use 2
• Dry mouth (14% vs 5% placebo) 2
• Weight gain (12% vs 10% placebo) 2

Critical contraindications and warnings:

• Pregnancy: Specifically contraindicated in early pregnancy per UK manufacturer guidelines 3
• Severe liver disease: Should be avoided due to inappropriate sedating effects 3
• Renal impairment: Dose should be halved in moderate-to-severe renal dysfunction 3
• Paradoxical reactions: Risk of increased agitation/rage, particularly in psychiatric populations 3

Key Clinical Pitfalls

• Do not use as PRN chemical restraint - this practice is prohibited per JCAHO standards 3
• Limited evidence base: Scientific support for hydroxyzine in anxiety is substantially weaker than for SSRIs/SNRIs 4, 7
• No withdrawal/rebound: Unlike benzodiazepines, abrupt discontinuation does not produce rebound anxiety or withdrawal symptoms 2
• Sedation profile: More sedating than modern first-line agents, which may impair daytime function 3

Practical Algorithm

For adult GAD:

1. First-line: SSRI (escitalopram, sertraline) or SNRI (venlafaxine, duloxetine) 3
2. If contraindications to antidepressants or patient preference: Consider hydroxyzine 50 mg/day 1, 2
3. Reassess efficacy at 4 weeks; do not continue beyond 4 months without systematic re-evaluation 1

For pediatric procedural anxiety:

1. First attempt: Non-pharmacological strategies (distraction, relaxation) 3
2. If inadequate: Hydroxyzine as approved anxiolytic option 3
3. Alternative: Nitrous oxide (though 20-30% failure rate) 3

For benzodiazepine withdrawal:

1. Progressive withdrawal preferred over abrupt 5
2. Add hydroxyzine 25 mg for marked anxiety or 50 mg for prominent withdrawal symptoms 5
3. Duration: 4 weeks during taper, then discontinue 5