Hydroxyzine for Anxiety Management
Hydroxyzine is NOT recommended as a first-line treatment for anxiety disorders and should not be used as a substitute for evidence-based therapies like SSRIs, SNRIs, or cognitive behavioral therapy. 1, 2
Evidence Base and Limitations
The evidence supporting hydroxyzine for anxiety is weak and outdated:
A 2010 Cochrane systematic review found hydroxyzine more effective than placebo for generalized anxiety disorder, BUT concluded it cannot be recommended as a reliable first-line treatment due to high risk of bias in included studies, small sample sizes, and limited number of trials. 3
The most recent controlled trials supporting hydroxyzine efficacy date from the 1990s, showing benefit at 50 mg daily for GAD with early cognitive symptom improvement. 4, 5 However, these studies predate modern anxiety treatment guidelines that prioritize SSRIs and SNRIs.
Current major anxiety treatment guidelines (American Academy of Child and Adolescent Psychiatry 2020, Japanese Society 2023) do not include hydroxyzine as a recommended treatment option, focusing instead on SSRIs and SNRIs as first-line pharmacotherapy. 1
Specific Clinical Concerns
Lack of Evidence for Specific Populations
- The American Academy of Child and Adolescent Psychiatry explicitly states that hydroxyzine lacks evidence for treating anger, irritability, or mood instability in adolescents and should NOT be used as a substitute for adequate antidepressant dosing when depression is present. 2
Cognitive and Safety Issues
Hydroxyzine causes CNS impairment, delirium, and sedation, particularly in older adults due to anticholinergic effects. 2 The Mayo Clinic rates this evidence as moderate strength.
Recent 2025 data shows hydroxyzine is now the most identified antihistamine in impaired driving investigations, associated with incoordination, slurred speech, erratic driving, and crashes. 6 Mean blood concentrations in these cases were 70 ng/mL.
The American Academy of Allergy, Asthma, and Immunology notes that first-generation antihistamines like hydroxyzine are associated with cognitive decline, particularly with long-term use and in elderly populations. 7
Drug Interaction Considerations
Hydroxyzine must be stopped 7-10 days before oral food challenge testing due to antihistamine properties. 2
The American Academy of Child and Adolescent Psychiatry recommends avoiding combining hydroxyzine with other anticholinergic medications to prevent cumulative effects. 7
When Hydroxyzine Might Be Considered (Limited Role)
If hydroxyzine is used despite limited evidence, specific parameters apply:
For benzodiazepine withdrawal support: One 1997 study showed hydroxyzine 50 mg reduced withdrawal symptoms and anxiety during lorazepam discontinuation, though no significant difference from placebo was found. 5
Dosing: 50 mg daily showed more consistent benefit than 25 mg in older trials. 4, 5
Duration: Should be shortest possible to minimize anticholinergic burden and cognitive effects. 7
Monitoring: Watch for daytime sleepiness (more frequent at 50 mg), sedation, and cognitive impairment. 5, 6
Preferred Evidence-Based Alternatives
SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (venlafaxine, duloxetine) are the recommended first-line pharmacological treatments for anxiety disorders in both adults and children/adolescents 6-18 years old, with high-quality evidence showing improvement in anxiety symptoms, treatment response, remission, and global function. 1