Can hydroxyzine be added to sertraline (Zoloft) for a patient with generalized anxiety disorder?

Yes, hydroxyzine can be safely added to sertraline (Zoloft) for generalized anxiety disorder

Hydroxyzine is an effective and well-tolerated augmentation option for GAD when added to sertraline, with demonstrated efficacy superior to placebo and a favorable safety profile that includes minimal drug interactions and no abuse potential. 1, 2

Evidence for Hydroxyzine in GAD

Hydroxyzine has demonstrated clear efficacy in treating generalized anxiety disorder:

• Controlled trials show hydroxyzine is significantly more effective than placebo (odds ratio 0.30,95% CI 0.15 to 0.58), with benefits appearing as early as the first week of treatment and maintained throughout 4 weeks 1, 2
• The medication targets the cognitive component of anxiety effectively, with particular benefit for early symptom reduction 2
• Fixed dosing at 50 mg daily has been validated in clinical trials, though typical regimens use 12.5 mg morning and midday with 25 mg evening 3

Safety of Combining Hydroxyzine with Sertraline

The combination presents minimal safety concerns compared to other augmentation strategies:

• Both medications can prolong the QTc interval, requiring baseline ECG monitoring in patients with cardiac risk factors, electrolyte abnormalities, or concurrent use of other QTc-prolonging medications 4
• Unlike combinations involving multiple serotonergic agents (e.g., adding buspirone or tricyclics to SSRIs), hydroxyzine does not increase serotonin syndrome risk since it works via antihistamine mechanisms 5
• Hydroxyzine demonstrates equivalent efficacy to benzodiazepines and buspirone but with no dependency potential or organ toxicity 2, 6

Practical Implementation

Start hydroxyzine while continuing sertraline at its current dose:

• Initiate hydroxyzine at 25 mg at bedtime to assess tolerability, then increase to 12.5 mg twice daily plus 25 mg at bedtime (total 50 mg/day) after 3-7 days 3
• The primary side effect is sedation/drowsiness, which can be beneficial for anxiety-related insomnia but may require dose timing adjustments 1
• Therapeutic response typically appears within 1 week, with maximal benefit by 4 weeks 2

Advantages Over Alternative Augmentation Strategies

Hydroxyzine offers several practical benefits in this clinical scenario:

• No risk of serotonin syndrome unlike adding buspirone, tricyclics, or switching to SNRIs 4, 5
• No abuse potential unlike benzodiazepines, making it appropriate for long-term use 2, 6
• Rapid onset of action (within 1 week) compared to buspirone which requires 2-4 weeks 2, 3
• Lower discontinuation rates due to side effects compared to other augmentation options 1

Monitoring Requirements

• Obtain baseline ECG if the patient has cardiac risk factors, takes other QTc-prolonging medications, or has electrolyte abnormalities 4
• Assess anxiety symptoms using standardized scales (e.g., Hamilton Anxiety Scale) at weeks 1,2, and 4 3
• Monitor for excessive sedation, particularly during the first week, and adjust timing of doses if needed 1

Common Pitfalls to Avoid

• Do not combine hydroxyzine with multiple other sedating medications without careful monitoring for excessive CNS depression 1
• Do not assume treatment failure before allowing 4 weeks at the target dose of 50 mg daily 2, 3
• Do not overlook the need for ECG monitoring in at-risk patients, as both sertraline and hydroxyzine can affect cardiac conduction 4