What is the recommended dosage and formulation of hydroxyzine (HCl or pamoate) for treating anxiety?

Hydroxyzine for Anxiety: Formulation and Dosing Recommendations

For anxiety treatment, hydroxyzine HCl and pamoate are equivalent formulations, with the FDA-approved dosage being 50-100 mg four times daily for adults, though current evidence suggests hydroxyzine should be considered a second-line or adjunctive option rather than first-line therapy. 1

FDA-Approved Dosing for Anxiety

Adults:

• 50-100 mg four times daily (QID) for symptomatic relief of anxiety and tension associated with psychoneurosis 1
• Dosage should be adjusted according to patient response 1

Pediatric Dosing:

• Children under 6 years: 50 mg daily in divided doses 1
• Children over 6 years: 50-100 mg daily in divided doses 1

HCl vs. Pamoate: No Clinically Significant Difference

The two salt forms (hydroxyzine hydrochloride and hydroxyzine pamoate) are bioequivalent and can be used interchangeably 1. The choice between formulations is typically based on availability rather than clinical superiority, as both deliver the same active medication.

Evidence for Efficacy in Generalized Anxiety Disorder

Hydroxyzine demonstrates efficacy superior to placebo in controlled trials, with anxiety reduction beginning within the first week of treatment at 50 mg daily 2, 3. The medication shows particular effectiveness for the cognitive component of anxiety 4. However, the quality of evidence is limited by high risk of bias in available studies, small sample sizes, and lack of long-term data 2.

When compared head-to-head with benzodiazepines and buspirone, hydroxyzine showed equivalent efficacy but was associated with higher rates of drowsiness 2. One trial demonstrated greater and more rapid cognitive improvement compared to lorazepam 4.

Current Clinical Position: Second-Line or Adjunctive Use

Hydroxyzine is not recommended as first-line treatment for anxiety disorders. Modern guidelines prioritize:

1. First-line: SSRIs (escitalopram, sertraline) or SNRIs (venlafaxine, duloxetine) 5, 6
2. First-line non-pharmacological: Cognitive behavioral therapy 7, 6
3. Second-line: Buspirone for mild-to-moderate anxiety (5 mg twice daily, maximum 20 mg three times daily, requiring 2-4 weeks for effect) 7, 5

Hydroxyzine is specifically recommended in these contexts:

• Pediatric anxiolysis for medical procedures: Approved for anxiolytic use in children undergoing diagnostic imaging or procedures, with few contraindications 7
• Benzodiazepine withdrawal support: Hydroxyzine 25-50 mg daily can reduce withdrawal symptoms and anxiety during lorazepam discontinuation 8
• Acute agitation management: As an adjunctive sedative agent in emergency settings 7
• Elderly patients requiring short-term anxiolysis: When benzodiazepines must be avoided due to fall risk or cognitive concerns 5

Practical Dosing Strategy

For GAD (when used):

• Start with 50 mg daily (the dose studied in controlled trials) 2, 3
• Can divide into 2-4 doses throughout the day 1
• Anxiolytic effect begins within the first week 3
• Maximum studied dose: 50 mg daily; FDA label allows up to 100 mg QID (400 mg/day total) 1, 3

For benzodiazepine withdrawal:

• Hydroxyzine 25 mg daily for markedly anxious patients 8
• Hydroxyzine 50 mg daily for patients with withdrawal symptomatology 8
• Use for 4-week withdrawal period 8

Side Effect Profile and Tolerability

Most common adverse effect: Transient daytime sleepiness/drowsiness (28% vs 14% placebo), which typically appears during the first week and progressively diminishes 2, 3

Other reported effects:

• Weight gain (12% vs 10% placebo) 3
• Dry mouth (14% vs 5% placebo) 3
• Loss of concentration (9% vs 8% placebo) 3
• Insomnia (9% vs 6% placebo) 3

Advantages over benzodiazepines:

• No dependency or withdrawal syndrome upon abrupt discontinuation 4, 3
• No rebound anxiety after stopping 3
• Lack of organ toxicity 4
• No tolerance development 7

Critical Limitations and Cautions

Why hydroxyzine is not first-line:

• Limited high-quality evidence (high risk of bias in available studies) 2
• Small number of controlled trials with small sample sizes 2
• Sedation can impair daytime functioning 2, 3
• Less effective than SSRIs/SNRIs for long-term anxiety management 6, 9

Special populations:

• Elderly: Use with extreme caution; sedation increases fall risk. Consider lower doses if used 7
• Patients with premature ventricular contractions: Use with caution (though this applies more to trazodone) 7
• Patients requiring cognitive performance: Sedation and concentration difficulties may be problematic 3

When to Choose Hydroxyzine Over Other Options

Consider hydroxyzine specifically when:

• Patient has contraindications to SSRIs/SNRIs 7
• Rapid anxiolysis needed for medical procedures in children 7
• Supporting benzodiazepine discontinuation 8
• Patient has history of substance use disorder (no addiction potential) 4
• Short-term anxiolysis needed (< 4 weeks) and benzodiazepines should be avoided 7, 2

Do not use hydroxyzine when:

• Long-term anxiety management is needed (use SSRIs/SNRIs instead) 6, 9
• Patient requires optimal daytime alertness 3
• First-line treatment has not been attempted 2