What is the recommended dosage and usage of Hydroxyzine (HCl) for treating anxiety and insomnia in adults, particularly those with impaired renal or liver function, or a history of seizures, glaucoma, or substance abuse?

Hydroxyzine HCl for Anxiety and Insomnia in Adults

Recommended Dosing for Anxiety

For symptomatic relief of anxiety and tension associated with psychoneurosis, hydroxyzine HCl is dosed at 50-100 mg four times daily in adults. 1

• The FDA-approved dosing for anxiety management is 50-100 mg QID (four times daily), which can be adjusted based on patient response 1
• Clinical trials have demonstrated efficacy at a fixed dose of 50 mg daily for generalized anxiety disorder, showing superiority over placebo from the first week of treatment 2
• Hydroxyzine 50 mg/day produces statistically and clinically significant anxiolytic effects that commence during the first week and are maintained throughout 4 weeks of treatment 3
• A 3-month double-blind study confirmed that hydroxyzine 50 mg/day demonstrated sustained efficacy with a mean Hamilton Anxiety Rating Scale (HAM-A) score reduction of -12.16 compared to -9.64 for placebo (p=0.019) 4

Recommended Dosing for Insomnia

Hydroxyzine is NOT recommended as a first-line treatment for insomnia based on current clinical practice guidelines. 5, 6

• The American Academy of Sleep Medicine explicitly states that over-the-counter antihistamines (including hydroxyzine) are not recommended for insomnia due to lack of efficacy data, strong anticholinergic effects, and safety concerns 5, 6
• When used as a sedative premedication, the FDA-approved dose is 50-100 mg for adults 1
• However, antihistamines cause daytime sedation, confusion, urinary retention, and fall risk, especially in elderly patients 6
• Tolerance to sedative effects develops after only 3-4 days of continuous use 6

Special Population Considerations

Renal Impairment

• Hydroxyzine dosing adjustments for renal impairment are not specifically detailed in the FDA label, but caution is warranted as the medication is metabolized and excreted 1
• Start with lower doses and titrate carefully based on clinical response and tolerability 1

Hepatic Impairment

• Patients with hepatic impairment require dose reduction as hydroxyzine undergoes hepatic metabolism 1
• Consider starting at 25 mg TID or QID rather than the standard 50-100 mg QID 1
• Monitor closely for excessive sedation and anticholinergic effects 1

History of Seizures

• Hydroxyzine should be used with extreme caution in patients with seizure disorders 1
• The medication can lower seizure threshold, particularly at higher doses 1
• If hydroxyzine must be used, start with the lowest effective dose and monitor seizure control closely 1

Glaucoma

• Hydroxyzine is contraindicated or should be avoided in patients with narrow-angle glaucoma due to its anticholinergic properties 1
• The anticholinergic effects can precipitate acute angle-closure glaucoma attacks 1
• If the patient has open-angle glaucoma and hydroxyzine is deemed necessary, use with caution and ophthalmologic monitoring 1

Substance Abuse History

• Hydroxyzine represents a safer alternative to benzodiazepines for patients with substance abuse history as it lacks dependency potential 2, 7
• Clinical experience has shown an absence of dependency with hydroxyzine, unlike benzodiazepines 2
• Hydroxyzine 25-50 mg can be used as transitional support during benzodiazepine withdrawal, with the 50 mg dose showing reduction in withdrawal symptomatology 8
• For anxiety in patients with addiction history, hydroxyzine is preferable to benzodiazepines, which carry significant risk of dependence and abuse 7, 4

Efficacy and Safety Profile

Anxiety Treatment

• Hydroxyzine demonstrated greater and more rapid cognitive improvement compared to lorazepam in controlled trials 2
• The medication shows efficacy maintained throughout 4 weeks of treatment with no rebound anxiety or withdrawal symptoms after abrupt discontinuation 3
• Hydroxyzine 50 mg/day showed comparable efficacy to bromazepam 6 mg/day over 3 months, with responder rates significantly better than placebo (p=0.003) 4

Tolerability

• The most common side effect is transient sleepiness (28% vs 14% with placebo), which appears during the first week and progressively diminishes 3
• Other side effects include weight gain (12%), dry mouth (14%), loss of concentration (9%), and insomnia (9%) 3
• Except for drowsiness, safety profiles are generally favorable with no organ toxicity reported 2, 4
• Drowsiness is more frequent with hydroxyzine 50 mg compared to 25 mg doses 8

Critical Clinical Considerations

When Hydroxyzine May Be Appropriate

• Generalized anxiety disorder in patients who cannot tolerate or have contraindications to SSRIs or benzodiazepines 2, 7, 4
• Anxiety in patients with substance abuse history where benzodiazepines are contraindicated 2, 8
• Transitional support during benzodiazepine withdrawal, using 25-50 mg doses to reduce withdrawal symptoms and anxiety 8
• Short-term anxiolysis as premedication at 50-100 mg doses 1

When to Avoid Hydroxyzine

• Primary insomnia treatment - use evidence-based alternatives like CBT-I, ramelteon, or low-dose doxepin instead 5, 6
• Elderly patients - increased risk of anticholinergic effects, confusion, falls, and urinary retention 6
• Narrow-angle glaucoma - anticholinergic effects can precipitate acute attacks 1
• Severe hepatic impairment - requires significant dose reduction or alternative therapy 1
• Active seizure disorder - can lower seizure threshold 1

Common Pitfalls to Avoid

• Using hydroxyzine as first-line insomnia treatment when evidence-based alternatives (CBT-I, ramelteon, low-dose doxepin) have superior efficacy and safety profiles 5, 6
• Failing to reduce doses in elderly patients or those with hepatic impairment, leading to excessive sedation and anticholinergic toxicity 1
• Prescribing to patients with narrow-angle glaucoma without ophthalmologic consultation 1
• Expecting sustained sedative effects for insomnia when tolerance develops after 3-4 days of continuous use 6
• Not considering hydroxyzine as a benzodiazepine alternative in patients with substance abuse history, where it offers anxiolytic effects without dependency risk 2, 8