What is the role of hydroxyzine in treating anxiety?

Hydroxyzine for Anxiety

Hydroxyzine is not recommended as a first-line treatment for anxiety disorders in adults or children, as it is notably absent from all major anxiety disorder treatment guidelines and lacks robust evidence for long-term efficacy. 1, 2

Guideline-Recommended First-Line Treatments

The evidence-based first-line treatments for anxiety disorders are:

• SSRIs (selective serotonin reuptake inhibitors) have the strongest evidence base for treating anxiety disorders in both adults and children, with considerable empirical support for safety and efficacy 1
• SNRIs (serotonin-norepinephrine reuptake inhibitors) have additional empirical support as a treatment option 1, 2
• Cognitive-behavioral therapy (CBT) is recommended as first-line treatment for mild to moderate anxiety, particularly in children 3

Limited Role of Hydroxyzine

FDA-Approved Indication

Hydroxyzine is FDA-approved for "symptomatic relief of anxiety and tension associated with psychoneurosis," but the FDA label explicitly states: "The effectiveness of hydroxyzine as an antianxiety agent for long term use, that is more than 4 months, has not been assessed by systematic clinical studies." 4

Evidence Quality

• A Cochrane systematic review found hydroxyzine more effective than placebo for generalized anxiety disorder (GAD), but concluded it cannot be recommended as a reliable first-line treatment due to high risk of bias in studies, small sample size, and limited number of trials 5
• Older studies from the 1990s showed some efficacy at 50 mg/day, but these had methodological limitations 6, 7

Appropriate Clinical Scenarios

Hydroxyzine may have a role in these specific situations:

• Short-term or situational anxiety management as an alternative to benzodiazepines 3, 2
• Anxiolysis during medical procedures in pediatric populations 2
• Adjunct to SSRIs for milder cases or as bridging therapy 3
• Benzodiazepine withdrawal support, where hydroxyzine 25-50 mg showed reduction in withdrawal symptoms and anxiety improvement 8

Safety Profile and Adverse Effects

Common side effects include:

• Drowsiness/sedation (28% vs 14% with placebo) - most common and typically transient, appearing in the first week 7, 3
• Dry mouth (14% vs 5% with placebo) 7
• Weight gain, loss of concentration, and insomnia 7

Important Contraindications

• Contraindicated in early pregnancy per UK manufacturer guidelines 2
• Avoid in severe liver disease due to inappropriate sedating effects 2
• Use lowest effective dose to minimize sedation 3
• Avoid combination with other anticholinergic medications 3

Critical Pitfalls to Avoid

• Do not use hydroxyzine as sole treatment for severe, chronic anxiety disorders where SSRIs/SNRIs would be more appropriate 3, 2
• Do not use as PRN chemical restraint in psychiatric settings - this practice is prohibited per JCAHO standards 2
• Be cautious about long-term use due to potential tolerance development and lack of evidence beyond 4 months 3, 4
• Do not assume hydroxyzine will reduce acute pain - a 2021 randomized trial showed adding hydroxyzine to morphine in prehospital settings did not reduce pain or anxiety 9

Clinical Algorithm

For new-onset anxiety disorders:

1. Start with SSRIs or SNRIs as first-line pharmacotherapy 1, 2
2. Consider CBT, especially for mild-moderate cases in children 3
3. Reserve hydroxyzine only for short-term situational anxiety or as adjunct therapy 3, 2

For benzodiazepine-dependent patients:

1. Consider hydroxyzine 25-50 mg as transitional support during withdrawal 8
2. Use progressive rather than abrupt withdrawal when possible 8

The sedation profile may impair daytime function, limiting its utility in patients requiring normal cognitive performance 2, 7