What is the recommended dosing, duration, and precautions for using hydroxyzine to treat anxiety?

Hydroxyzine for Anxiety: Dosing, Duration, and Precautions

Hydroxyzine at 50 mg daily is an effective anxiolytic for generalized anxiety disorder with onset of action within the first week, but it should be used cautiously in older adults due to significant anticholinergic risks and is not recommended as first-line therapy in adolescents.

Recommended Dosing

For adults with generalized anxiety disorder, hydroxyzine 50 mg daily is the evidence-based dose that demonstrates both statistical and clinical efficacy 1, 2. This fixed dose showed superiority over placebo across all anxiety measures starting from the first week of treatment 1.

• The anxiolytic effect begins during the first week and is maintained throughout treatment 1
• For elderly or debilitated patients, lower doses (10-50 mg at night) should be considered due to increased risk of CNS impairment and anticholinergic effects 3
• Hydroxyzine can be dosed up to a maximum of 200 mg daily in divided doses for more severe presentations, though this is more sedating 3

Duration of Treatment

Hydroxyzine has been studied and proven effective for up to 3 months of continuous treatment 2. The 3-month double-blind trial demonstrated maintained efficacy throughout the 12-week period with comparable safety to placebo except for drowsiness 2.

• Efficacy persists after abrupt discontinuation without rebound anxiety or withdrawal symptoms 1
• Unlike benzodiazepines, hydroxyzine does not cause dependency with prolonged use 4
• Treatment duration should be reassessed periodically, though no specific maximum duration is established in guidelines

Critical Precautions and Contraindications

Age-Related Concerns

The Mayo Clinic identifies hydroxyzine as causing CNS impairment, delirium, and sedation in older adults due to anticholinergic effects (moderate strength of evidence) 5. This makes it a problematic choice in geriatric populations despite its efficacy.

• Anticholinergic burden is cumulative and affects memory and cognitive function, particularly concerning with long-term use 6
• In adolescents, hydroxyzine lacks evidence for treating mood instability and should not substitute for adequate antidepressant dosing when depression is present 5

Common Side Effects

The most frequent adverse effect is transient drowsiness/sleepiness, occurring in approximately 28% of patients compared to 14% with placebo 1.

• Drowsiness typically appears during the first week and progressively diminishes with continued treatment 1
• Other side effects include weight gain (12%), dry mouth (14%), loss of concentration (9%), and insomnia (9%) 1
• Hydroxyzine causes more sleepiness than benzodiazepines like bromazepam 2

Drug Interactions and Special Warnings

Hydroxyzine has alpha-adrenergic antagonism activity, which creates a risk of priapism when combined with antipsychotics like risperidone 7. This represents a serious but rare adverse event requiring immediate medical attention.

• Avoid combining with other anticholinergic medications to prevent cumulative cognitive effects 6
• Discontinue hydroxyzine 7-10 days before oral food challenge testing due to antihistamine properties that can interfere with results 5
• Use with caution in patients with cardiac disease, as other antihistamines in its class can affect cardiac conduction 3

Comparative Efficacy

Hydroxyzine demonstrates equivalent efficacy to benzodiazepines (bromazepam, chlordiazepoxide) and buspirone for generalized anxiety disorder 8, 2.

• The advantage over benzodiazepines is the absence of dependency risk and withdrawal symptoms 2, 4
• Hydroxyzine shows greater and more rapid cognitive improvement compared to lorazepam 4
• However, a Cochrane review noted high risk of bias in available studies, limiting the strength of recommendation as first-line therapy 8

Clinical Algorithm for Use

1. First-line consideration: Reserve for adult patients with GAD who cannot tolerate or have contraindications to SSRIs, or as an alternative to benzodiazepines when dependency is a concern 2

2. Avoid in: Older adults (due to anticholinergic burden), adolescents with mood disorders, patients on multiple anticholinergic medications, and those with significant cardiac disease 5, 6

3. Starting approach: Begin with 50 mg daily, taken at bedtime if sedation is problematic 1, 2

4. Monitoring: Assess for drowsiness in first week (typically transient), cognitive effects (especially in elderly), and anxiety response by end of week one 1

5. Duration: Continue for 3 months if effective, then reassess need for ongoing treatment 2