In an otherwise healthy adult without severe liver or kidney disease, substance‑use disorder, pregnancy, or benzodiazepine dependence, can hydroxyzine be used PRN for acute anxiety and depression?

Hydroxyzine for PRN Use in Anxiety and Depression

Hydroxyzine can be used PRN for acute anxiety symptoms in otherwise healthy adults, but it should not be used for depression and is not a first-line treatment for anxiety disorders. 1, 2

Evidence for Hydroxyzine in Anxiety

Hydroxyzine is more effective than placebo for generalized anxiety disorder (GAD) but carries significant limitations that restrict its role to adjunctive or short-term use. 2

• A Cochrane systematic review found hydroxyzine superior to placebo for GAD (OR 0.30,95% CI 0.15 to 0.58), with comparable efficacy to benzodiazepines and buspirone. 2
• However, the review concluded that due to high risk of bias in included studies, small sample sizes, and limited evidence, hydroxyzine cannot be recommended as a reliable first-line treatment for GAD. 2
• Hydroxyzine is associated with higher rates of sleepiness/drowsiness compared to other anxiolytics (OR 1.74,95% CI 0.86 to 3.53), which limits its utility for daytime PRN use. 2

First-Line Treatments for Anxiety

SSRIs (sertraline, citalopram, escitalopram, fluoxetine, fluvoxamine, or paroxetine) are the recommended first-line pharmacotherapy for anxiety disorders, not hydroxyzine. 1

• Cognitive behavioral therapy (CBT) is the preferred first-line psychotherapy for anxiety disorders. 1
• Combination therapy with CBT plus SSRI may be offered preferentially over monotherapy for patients with social anxiety, generalized anxiety, separation anxiety, or panic disorder. 1

Role of Hydroxyzine vs. Benzodiazepines for PRN Use

If PRN anxiolytic medication is needed, benzodiazepines are more evidence-based than hydroxyzine for acute anxiety stabilization, but both carry significant caveats. 1, 3

• Benzodiazepines should be reserved for short-term adjunctive use during the initial 6-8 weeks of SSRI treatment to bridge until antidepressant effect is achieved, or for acute stabilization in severe cases. 3
• Benzodiazepines should never be used as monotherapy or long-term treatment due to dependence risk and withdrawal complications. 3
• PRN benzodiazepine use is common in clinical practice but may be associated with increased patient preference for continued use, greater cognitive impairment, and potentially reduced anxiolytic efficacy over time. 4
• Benzodiazepines are absolutely contraindicated in patients with substance use disorder due to high risk of overdose when combined with opioids and significant dependence potential. 3

Hydroxyzine Has No Role in Depression

Neither hydroxyzine nor benzodiazepines should be used for depression. 5

• WHO guidelines explicitly state that neither antidepressants nor benzodiazepines should be used for the initial treatment of individuals with complaints of depressive symptoms in absence of current/prior depressive episode/disorder. 5
• For mild depressive episodes, antidepressants should not be considered for initial treatment. 5
• For moderate to severe depressive episodes, tricyclic antidepressants or fluoxetine should be considered, not hydroxyzine. 5

Clinical Algorithm for PRN Anxiolytic Use

When an otherwise healthy adult presents with acute anxiety:

1. Rule out medical causes such as unrelieved pain, fatigue, delirium, infection, or electrolyte imbalance before initiating anxiolytic treatment. 1

2. Initiate SSRI therapy as first-line pharmacotherapy for anxiety disorders. 1

3. Consider short-term adjunctive benzodiazepine (not hydroxyzine) for acute stabilization during the first 6-8 weeks while waiting for SSRI effect, with the following caveats: 1, 3

   • Limit to 2-4 weeks maximum duration. 6
   • Use lowest effective dose. 6
   • Avoid in elderly due to fall risk and cognitive impairment. 3
   • Avoid in patients with hepatic impairment (or use lorazepam instead of diazepam). 3
   • Avoid in patients with respiratory compromise. 3
   • Absolutely contraindicated in substance use disorder. 3

4. Hydroxyzine may be considered as an alternative to benzodiazepines for PRN use if: 2

   • The patient has contraindications to benzodiazepines (e.g., substance use history). 3
   • Sedation is acceptable or desired. 2
   • The patient understands it is not first-line therapy and has limited evidence. 2

5. Refer for CBT as the preferred first-line psychotherapy, ideally in combination with pharmacotherapy. 1

Common Pitfalls to Avoid

• Do not use hydroxyzine or any anxiolytic for depression—this is ineffective and delays appropriate treatment. 5
• Do not prescribe benzodiazepines long-term—tolerance, dependence, and withdrawal effects become major disadvantages beyond 4 weeks. 6
• Do not use PRN anxiolytics as monotherapy—they should always be adjunctive to SSRIs and/or CBT. 3
• Do not overlook cardiovascular considerations—in patients with cardiovascular disease, sertraline is preferred over citalopram or escitalopram due to lower risk of QTc prolongation. 5