Is hydroxyzine or propranolol better for treating anxiety?

Hydroxyzine vs Propranolol for Anxiety: Evidence-Based Recommendation

For treating generalized anxiety disorder, hydroxyzine is superior to propranolol based on controlled trial evidence demonstrating anxiolytic efficacy, while propranolol lacks proven central anxiolytic effects and only addresses peripheral somatic symptoms.

Primary Recommendation

Hydroxyzine should be the preferred choice for anxiety treatment when comparing these two agents. 1, 2 The FDA has approved hydroxyzine specifically for "symptomatic relief of anxiety and tension associated with psychoneurosis," whereas propranolol is not FDA-approved for anxiety disorders. 1

Evidence Supporting Hydroxyzine

• Proven anxiolytic efficacy: Hydroxyzine demonstrates statistically significant superiority over placebo for generalized anxiety disorder (OR 0.30,95% CI 0.15 to 0.58), with benefits appearing within the first week of treatment at 50 mg/day. 2, 3

• Rapid onset: Anxiety score reductions become significant by the end of week one and are maintained throughout 4 weeks of treatment, with no rebound anxiety or withdrawal symptoms upon abrupt discontinuation. 4, 3

• Cognitive benefits: Hydroxyzine targets the cognitive component of anxiety and demonstrates greater and more rapid cognitive improvement compared to benzodiazepines in controlled trials. 4

• Acceptable tolerability: The most common side effect is transient sleepiness (28% vs 14% placebo), which typically appears during the first week and progressively resolves with continued treatment. 3

Evidence Against Propranolol

• Lack of central anxiolytic action: In controlled CO2 anxiety provocation studies, propranolol 40 mg failed to reduce subjective anxiety measures despite significantly decreasing heart rate, supporting that its effects are purely peripheral rather than centrally anxiolytic. 5

• Limited clinical utility: Beta-blockers like propranolol are deprecated by Canadian guidelines for social anxiety disorder based on negative evidence. 6

• Narrow indication: Propranolol only ameliorates somatic symptoms such as palpitations and tremor, not the core cognitive and emotional components of anxiety. 7

Clinical Context Where Propranolol May Be Considered

Propranolol has a specific but limited role in anxiety management:

• Performance anxiety with prominent somatic symptoms: When palpitations, tremor, or tachycardia are the primary concern (e.g., public speaking, musical performance), propranolol may address these peripheral manifestations. 8, 7

• Post-acute sequelae of COVID-19 with orthostatic intolerance: Low-dose beta-blockers including propranolol may help control debilitating symptoms in hyperadrenergic states, particularly when coexisting anxiety or migraine is present. 8

• Adjunctive use: Propranolol may be added to address residual somatic symptoms in patients already receiving appropriate anxiolytic therapy. 7

Important Caveats and Monitoring

For Hydroxyzine:

• Duration limitation: The FDA label notes that effectiveness as an antianxiety agent for long-term use (more than 4 months) has not been assessed by systematic clinical studies, requiring periodic reassessment. 1

• Sedation management: Expect transient sleepiness during the first week; counsel patients that this typically resolves with continued treatment. 3

• Dosing: Standard effective dose is 50 mg/day for generalized anxiety disorder. 4, 3

For Propranolol:

• Blood pressure monitoring: When used for any indication, monitor for hypotension and bradycardia. 8

• Contraindications: Avoid in patients with asthma, heart block, or severe bradycardia. 8

• Not a substitute for anxiolytics: Do not use propranolol as monotherapy for generalized anxiety disorder or other primary anxiety disorders. 5

First-Line Treatment Context

Neither hydroxyzine nor propranolol represents optimal first-line pharmacotherapy for anxiety disorders:

• SSRIs/SNRIs are first-line: Escitalopram, sertraline, duloxetine, and venlafaxine have the strongest evidence base for anxiety disorders with favorable safety profiles. 6

• Combination with CBT: Optimal outcomes require combining pharmacotherapy with cognitive behavioral therapy specifically targeting anxiety patterns. 6

• Hydroxyzine as alternative: When SSRIs/SNRIs are contraindicated, not tolerated, or in patients with previous substance dependence history, hydroxyzine represents a reasonable non-benzodiazepine option. 2, 7