Hydroxyzine's Role in Treating Anxiety
Hydroxyzine is an effective second-line treatment option for anxiety disorders, particularly for short-term management, but should not be used as first-line therapy due to its limited long-term efficacy data and sedative effects.
Mechanism and FDA Approval
Hydroxyzine is a first-generation antihistamine that has FDA approval for the "symptomatic relief of anxiety and tension associated with psychoneurosis" 1. Its anxiolytic effects are believed to be related to its antihistaminic properties and central nervous system depression.
Efficacy in Anxiety Disorders
Evidence for Effectiveness
- Hydroxyzine has demonstrated superiority over placebo in generalized anxiety disorder (GAD), with significant improvement in anxiety symptoms beginning within the first week of treatment 2
- A Cochrane review found hydroxyzine more effective than placebo for GAD (odds ratio 0.30,95% CI 0.15 to 0.58) 3
- Hydroxyzine showed comparable efficacy to benzodiazepines and buspirone in some studies 3
Limitations of Evidence
- The FDA label notes that "the effectiveness of hydroxyzine as an antianxiety agent for long-term use (more than 4 months) has not been assessed by systematic clinical studies" 1
- The Cochrane review highlighted concerns about the high risk of bias in available studies, small number of studies, and small sample sizes 3
Clinical Applications
Appropriate Use Cases
- Short-term management of anxiety symptoms
- Adjunctive therapy for breakthrough anxiety during initiation of first-line treatments
- Patients who cannot tolerate or have contraindications to first-line treatments (SSRIs/SNRIs)
- Patients with comorbid pruritus or allergic conditions who may benefit from hydroxyzine's antihistaminic properties
Not Recommended For
- First-line treatment of anxiety disorders
- Long-term management of chronic anxiety
- Primary treatment when more evidence-based options are available and appropriate
Treatment Approach
Dosing and Administration
- Typical starting dose: 25-50 mg daily, divided into multiple doses
- Can be titrated based on response and tolerability
- Available in tablet and syrup formulations
Monitoring
- Assess for sedation, particularly during initial treatment
- Monitor for anticholinergic side effects
- Evaluate treatment response within 1-2 weeks
Comparison to First-Line Treatments
Current guidelines recommend SSRIs and SNRIs as first-line pharmacotherapy for anxiety disorders 4, 5:
- SSRIs (escitalopram, sertraline, paroxetine, fluoxetine) have stronger evidence for long-term efficacy
- SNRIs (venlafaxine) show comparable efficacy to SSRIs
- Cognitive behavioral therapy (CBT) is highly effective and recommended as first-line treatment, either alone or in combination with medication 5
Side Effects and Precautions
Common Side Effects
- Sedation/drowsiness (more common than with other anxiolytics) 3
- Dry mouth
- Dizziness
- Weight gain
- Cognitive impairment
Special Populations
- Use with caution in elderly patients due to increased risk of falls and anticholinergic effects
- May be useful in pediatric patients for anxiolysis during medical procedures 4
- Use caution in patients with cardiac conditions due to potential QT prolongation
Clinical Pearls
- Hydroxyzine's sedative effects can be beneficial for patients with anxiety-related insomnia
- Unlike benzodiazepines, hydroxyzine does not cause dependence or withdrawal symptoms upon discontinuation 2
- Can be used as a bridge therapy while waiting for SSRIs/SNRIs to reach full effectiveness (typically 4-6 weeks)
- May be particularly useful in situations requiring short-term anxiolysis, such as medical procedures 6
Conclusion
While hydroxyzine has demonstrated efficacy for anxiety, current guidelines favor SSRIs, SNRIs, and CBT as first-line treatments for anxiety disorders due to their stronger evidence base 4, 5. Hydroxyzine should be considered a second-line or adjunctive option, particularly for short-term management or in patients who cannot tolerate first-line treatments.