What is the role of hydroxyzine in treating a patient with anxiety?

Hydroxyzine for Anxiety Treatment

Primary Recommendation

Hydroxyzine is FDA-approved for symptomatic relief of anxiety and tension associated with psychoneurosis and can be used as adjunctive therapy in organic disease states where anxiety is manifested, though its effectiveness for long-term use (beyond 4 months) has not been established by systematic clinical studies. 1

Evidence-Based Efficacy

Hydroxyzine demonstrates statistically significant anxiolytic effects compared to placebo in generalized anxiety disorder (GAD):

• Hydroxyzine 50 mg daily shows superiority over placebo beginning in the first week of treatment (OR 0.30,95% CI 0.15 to 0.58), with anxiety reduction maintained throughout 4 weeks and persisting after abrupt discontinuation without rebound or withdrawal symptoms 2, 3

• The anxiolytic effect targets cognitive components of anxiety specifically, including worry, tension, and apprehension, with early symptom improvement 4

• Hydroxyzine demonstrates equivalent efficacy to benzodiazepines (chlordiazepoxide) and buspirone for GAD treatment (OR 0.75,95% CI 0.35 to 1.62 vs chlordiazepoxide; OR 0.76,95% CI 0.40 to 1.42 vs buspirone) 2

Clinical Context and Positioning

Hydroxyzine occupies a limited niche role in anxiety management rather than serving as first-line treatment:

• Current anxiety disorder guidelines recommend SSRIs, SNRIs, or psychotherapy as first-line interventions for GAD, social anxiety disorder, separation anxiety disorder, and panic disorder 5

• Hydroxyzine is primarily reserved for acute anxiolysis in specific clinical scenarios: pediatric procedural anxiety (approved for anxiolytic use in children), acute agitation management, or as adjunctive therapy during benzodiazepine withdrawal 5, 6

• The medication lacks the robust evidence base supporting SSRIs/SNRIs for anxiety disorders, with high risk of bias in available studies and small overall sample sizes 2

Dosing and Administration

Standard dosing for anxiety treatment:

• Hydroxyzine 50 mg daily (divided doses or single dose) for GAD in adults 1, 3, 4
• Hydroxyzine 25 mg daily may be considered for markedly anxious patients or as support during benzodiazepine withdrawal 6
• Pediatric dosing for procedural anxiolysis follows institutional protocols with appropriate weight-based calculations 5

Adverse Effect Profile

The most common adverse effect is transient sedation:

• Sleepiness/drowsiness occurs in 28% of patients (vs 14% placebo), typically appearing during the first week and progressively diminishing with continued treatment 3
• Other side effects include dry mouth (14% vs 5% placebo), weight gain (12% vs 10%), loss of concentration (9% vs 8%), and insomnia (9% vs 6%) 3
• Hydroxyzine demonstrates higher rates of sedation compared to benzodiazepines and buspirone (OR 1.74,95% CI 0.86 to 3.53) 2

Critical safety consideration:

• Both hydroxyzine and escitalopram (or other SSRIs) can prolong the QTc interval, requiring caution when used together, particularly in patients with cardiac risk factors, electrolyte abnormalities, or concurrent use of other QTc-prolonging medications 7
• Baseline ECG monitoring may be warranted in high-risk patients receiving combination therapy 7

Acceptability and Tolerability

Hydroxyzine demonstrates acceptable tolerability profiles:

• Treatment discontinuation rates are equivalent to placebo (OR 1.00,95% CI 0.63 to 1.58) 2
• Side effect-related discontinuation occurs at similar rates to placebo (OR 1.49,95% CI 0.92 to 2.40) 2
• Hydroxyzine lacks abuse potential, dependence risk, and withdrawal symptoms—critical advantages over benzodiazepines 1, 3, 4

Duration of Treatment

The FDA label explicitly states that hydroxyzine's effectiveness as an antianxiety agent for long-term use (more than 4 months) has not been assessed by systematic clinical studies, and physicians should periodically reassess the drug's usefulness for individual patients 1

Specific Clinical Scenarios

Benzodiazepine withdrawal support:

• Hydroxyzine 50 mg daily reduces withdrawal symptomatology and anxiety during lorazepam discontinuation, with significant improvement in side effects compared to placebo 6
• Hydroxyzine 25 mg daily can be offered to markedly anxious patients during benzodiazepine taper 6

Pediatric procedural anxiety:

• Hydroxyzine is approved for anxiolytic use in children and is commonly used for procedural sedation in nuclear medicine and imaging procedures 5
• Available in tablets and syrup formulations with few contraindications in pediatric populations 5

Acute agitation management:

• Hydroxyzine serves as a less commonly used alternative to benzodiazepines and antipsychotics for chemical restraint in pediatric behavioral emergencies, though controlled trial data are limited to adult populations 5

Critical Limitations

Due to high risk of bias in available studies, small number of trials, and overall small sample sizes, hydroxyzine cannot be recommended as a reliable first-line treatment for GAD 2

The evidence base consists primarily of older studies (1990s) with methodological limitations, and hydroxyzine is notably absent from contemporary anxiety disorder treatment guidelines as a primary intervention 5

Drug Interactions

Hydroxyzine may potentiate meperidine and barbiturates when used as premedication or following general anesthesia, requiring individualized dose modification 1

Hydroxyzine does not interfere with digitalis action and may be used concurrently 1

Atropine and other belladonna alkaloids are not affected by hydroxyzine 1