Hydroxyzine Dosage for Generalized Anxiety in Adults
For generalized anxiety disorder in adults without hepatic or renal impairment, the standard off-label dose of hydroxyzine is 50-100 mg divided into four times daily (QID), with most evidence supporting 50 mg daily as the effective starting dose. 1
FDA-Approved Dosing for Anxiety
The FDA label specifies that for symptomatic relief of anxiety and tension associated with psychoneurosis, the adult dose is 50-100 mg four times daily (QID) 1. This translates to a total daily dose range of 200-400 mg, though clinical practice typically uses lower doses.
Evidence-Based Dosing from Clinical Trials
The most robust evidence supports 50 mg daily as an effective dose for GAD:
Multiple controlled trials demonstrated that hydroxyzine 50 mg/day (administered as 12.5 mg morning and midday, 25 mg evening) produces statistically and clinically significant anxiolytic effects beginning in the first week of treatment 2, 3
This dosing regimen showed superiority over placebo on all anxiety measures from week one, with efficacy maintained throughout 4 weeks of treatment 2
The 50 mg daily dose did not produce rebound anxiety or withdrawal symptoms upon abrupt discontinuation 2
Practical Dosing Algorithm
Start with 50 mg daily divided as:
- 12.5 mg in morning
- 12.5 mg at midday
- 25 mg in evening 3
If inadequate response after 1 week, titrate to:
- 25 mg three times daily (75 mg total)
- Maximum: 25 mg QID (100 mg total daily) 1
The evening dose should be higher to address nighttime anxiety and promote sleep, while lower daytime doses minimize sedation 3.
Efficacy Timeline and Monitoring
- Onset of action: Significant anxiety reduction occurs within the first week of treatment 2
- Peak effect: Maintained throughout 4 weeks with continued improvement 2
- Early target symptoms: Hydroxyzine preferentially improves the cognitive component of anxiety (worry, concentration difficulties) 4
Common Pitfalls and Side Effects
Transient sedation is the most common side effect:
- Occurs in approximately 28% of patients (vs 14% with placebo) 2
- Appears during the first week and progressively diminishes with continued treatment 2
- This tolerance to sedation is critical to communicate to patients to prevent premature discontinuation
Other side effects include:
- Dry mouth (14% vs 5% placebo) 2
- Weight gain (12% vs 10% placebo) 2
- Loss of concentration (9% vs 8% placebo) 2
Comparative Efficacy
When compared head-to-head with benzodiazepines and buspirone:
- Hydroxyzine demonstrated equivalent anxiolytic efficacy to lorazepam and buspirone 5, 3
- Hydroxyzine showed greater and more rapid cognitive improvement compared to lorazepam 4, 6
- Unlike benzodiazepines, hydroxyzine has no dependency potential and no withdrawal syndrome upon discontinuation 4, 2
Duration of Treatment
Clinical trials evaluated 4-week treatment periods with maintained efficacy throughout 2, 3. For chronic GAD, treatment duration should be based on symptom response, but hydroxyzine's lack of dependency makes it suitable for longer-term use compared to benzodiazepines 4.
Important Caveats
While hydroxyzine shows efficacy, the evidence base has limitations:
- A Cochrane review noted high risk of bias in included studies and small overall sample size 5
- The review concluded hydroxyzine cannot be recommended as a reliable first-line treatment despite being more effective than placebo 5
In clinical practice, hydroxyzine is best positioned as:
- An alternative when SSRIs/SNRIs are contraindicated or not tolerated
- Adjunctive therapy for acute anxiety symptoms
- Short-term use while initiating first-line antidepressant therapy