What is the recommended dosing and effectiveness of hydroxyzine (an antihistamine) for anxiety?

Hydroxyzine Dosing and Effectiveness for Anxiety

Hydroxyzine is effective for generalized anxiety disorder at a dose of 50 mg daily, demonstrating superiority over placebo with onset of anxiolytic effects within the first week of treatment. 1, 2

Recommended Dosing

The standard therapeutic dose for anxiety is 50 mg daily, which can be administered as a single dose or divided throughout the day. 1, 2

• Starting dose: 25 mg may be appropriate for elderly patients or those sensitive to sedative effects 3
• Standard adult dose: 50 mg daily has been validated in controlled trials for generalized anxiety disorder 2
• Bedtime dosing: 50-100 mg at bedtime can provide dual benefits for patients with comorbid anxiety and insomnia 3
• Onset of action: Effects begin approximately 15-30 minutes after oral administration, lasting 4-6 hours 3

Clinical Effectiveness

Hydroxyzine demonstrates statistically significant anxiolytic efficacy compared to placebo, with particular effectiveness on cognitive symptoms of anxiety. 4, 5, 2

• Anxiety reduction is evident from the first week of treatment and maintained throughout 4 weeks 2
• The medication shows superiority over placebo on all anxiety rating scales (HARS, Zung) 2
• Hydroxyzine targets cognitive components of anxiety more rapidly than some comparators, with greater and more rapid cognitive improvement than lorazepam in one trial 5
• Efficacy is maintained after abrupt discontinuation without rebound anxiety or withdrawal symptoms 2
• The medication is equivalent in efficacy to benzodiazepines (chlordiazepoxide) and buspirone 4

However, the evidence base has significant limitations: A Cochrane review concluded that due to high risk of bias in included studies, small sample sizes, and limited number of trials, hydroxyzine cannot be recommended as a reliable first-line treatment despite showing superiority over placebo 4

Special Clinical Considerations

Hydroxyzine's anticholinergic effects may provide better control of somatic anxiety symptoms (trembling, physical tension) compared to second-generation antihistamines. 3

• The sedative properties make it particularly useful for patients with comorbid anxiety and insomnia 3
• It can serve as a transitional agent during benzodiazepine withdrawal, with the 50 mg dose reducing withdrawal symptomatology 6
• The FDA label indicates effectiveness has not been assessed for long-term use beyond 4 months 1

Tolerability and Side Effects

The most common side effect is transient sleepiness (28% vs 14% with placebo), which typically appears during the first week and progressively diminishes with continued treatment. 2

• Other reported side effects include: dry mouth (14%), weight gain (12%), loss of concentration (9%), and insomnia (9%) 2
• Overall acceptability is comparable to placebo, with no significant difference in discontinuation rates 4
• Hydroxyzine demonstrates an absence of dependency and lack of organ toxicity 5

Contraindications and Precautions

Hydroxyzine should be used with caution in elderly patients due to increased susceptibility to anticholinergic effects. 7, 3

• Contraindicated: Closed-angle glaucoma, prostatic hypertrophy (use with caution) 3
• Avoid in: Severe liver disease (sedating effect is inappropriate), severe renal impairment (dose should be halved in moderate renal impairment) 7
• Pregnancy: Specifically contraindicated during early pregnancy per UK manufacturer guidelines 7
• Elderly considerations: Higher risk of cognitive impairment and anticholinergic effects 3

Practical Prescribing Algorithm

For new patients with generalized anxiety disorder:

• Start with 50 mg daily (or 25 mg in elderly/sensitive patients) 2, 3
• Assess response at 1 week (when anxiolytic effects should be evident) 2
• If insomnia is prominent, administer the dose at bedtime 3
• Continue for up to 4 weeks for acute symptom management 1, 2
• Reassess periodically if considering use beyond 4 months 1