What is a reasonable starting dose of hydroxyzine (antihistamine) for an adult patient with generalized anxiety disorder?

Hydroxyzine Dosing for Generalized Anxiety Disorder in Adults

For an adult patient with generalized anxiety disorder, start hydroxyzine at 50 mg four times daily (total 200 mg/day), which is the FDA-approved dosing regimen that has demonstrated efficacy in controlled trials. 1

Standard Dosing Regimen

• The FDA-approved dose for anxiety and tension associated with psychoneurosis is 50-100 mg four times daily in adults 1
• Clinical trials demonstrating efficacy used a fixed dose of 50 mg daily (likely divided), showing superiority over placebo from the first week of treatment 2, 3
• The onset of action occurs within 15-30 minutes after oral administration, with effects lasting 4-6 hours 4, 5

Dose Modifications for Special Populations

Elderly or sedation-sensitive patients:

• Start with 25 mg to assess tolerance, particularly due to increased susceptibility to anticholinergic effects 4, 5
• The elderly are more vulnerable to cognitive impairment and anticholinergic side effects 4

Patients with comorbid insomnia:

• Consider administering 50-100 mg at bedtime to provide dual benefits for both anxiety and sleep disturbance 4, 5
• Hydroxyzine's sedative properties make it particularly useful when insomnia accompanies anxiety 4

Clinical Efficacy Profile

• Hydroxyzine demonstrates statistical superiority over placebo on all anxiety rating measures, with benefits appearing within the first week 2, 3
• The medication targets cognitive components of anxiety effectively 3
• Efficacy is maintained throughout 4 weeks of treatment and persists after abrupt discontinuation without rebound anxiety or withdrawal symptoms 2
• Compared to benzodiazepines (chlordiazepoxide) and buspirone, hydroxyzine shows equivalent efficacy 6

Tolerability and Side Effects

Common adverse effects:

• Sleepiness/drowsiness occurs in 28% of patients (vs 14% with placebo), typically appearing during the first week and progressively diminishing with continued treatment 2
• Dry mouth affects 14% (vs 5% placebo) 2
• Weight gain occurs in 12% (vs 10% placebo) 2
• Hydroxyzine causes more sedation than other anxiolytics like buspirone or benzodiazepines 6

The anticholinergic effects may actually provide better control of somatic anxiety symptoms (trembling, autonomic symptoms) compared to second-generation antihistamines 4, 5

Absolute Contraindications

Hydroxyzine must be avoided in:

• Closed-angle glaucoma 4, 5
• Prostatic hypertrophy 4, 5
• Early pregnancy (per UK manufacturer guidelines) 4
• Severe liver disease 4
• Severe renal impairment 4

Critical Prescribing Caveats

• Hydroxyzine should not be used as monotherapy for major depressive disorder—it does not constitute adequate treatment for comorbid depression 4
• Paradoxical agitation can occur, particularly in younger patients, though this is rare 4
• The medication requires dose adjustment according to individual patient response 1
• While effective, the evidence base has high risk of bias and small sample sizes, limiting the strength of recommendation as a first-line agent 6

Position in Treatment Algorithm

Hydroxyzine represents an alternative to benzodiazepines when short-term anxiolytic treatment is needed, particularly valuable in patients with:

• Comorbid insomnia requiring sedation 4
• Prominent somatic anxiety symptoms 4, 5
• Cognitive or addictive problems where benzodiazepines should be avoided 7
• Need for non-addictive anxiolytic without dependency risk 3

However, for chronic GAD requiring long-term treatment, SSRIs or SNRIs remain preferred first-line options based on current evidence 8, 7.