Hydroxyzine (Atarax): A First-Generation Antihistamine with Sedative Properties
Hydroxyzine (Atarax) is a first-generation antihistamine with significant sedative properties that is primarily used for anxiety disorders, pruritus (itching), and as a pre-procedural sedative, but should be used with caution due to its potential for sedation, performance impairment, and anticholinergic effects.
Pharmacology and Mechanism of Action
Hydroxyzine is chemically unrelated to phenothiazines, reserpine, meprobamate, or benzodiazepines 1. It works through:
- Antihistamine effects (H1-receptor antagonism)
- Suppression of activity in key regions of the subcortical central nervous system
- Mild skeletal muscle relaxation
- Bronchodilator activity
- Analgesic effects
- Antiemetic properties
The medication is rapidly absorbed from the gastrointestinal tract with clinical effects usually noted within 15-30 minutes after oral administration 1.
Clinical Indications
Hydroxyzine is indicated for:
Anxiety disorders
Pruritus (itching)
Pre-procedural sedation
- Used for anxiolysis before medical procedures
- Particularly useful in pediatric patients 2
Insomnia
- Considered a weak treatment option compared to other medications 2
Dosing Considerations
- Anxiety: Typically 50mg/day 2
- Insomnia: 25-100mg at bedtime 2
- Pruritus in children: 0.7 mg/kg three times daily has shown efficacy similar to higher doses with less sedation 5
- Reduced dosing required in:
- Elderly patients
- Hepatic impairment
- Renal impairment 2
Important Safety Considerations
Sedation and Performance Impairment
First-generation antihistamines like hydroxyzine have significant potential for:
- Sedation and drowsiness
- Performance impairment (even without subjective awareness of drowsiness)
- Impaired learning and school performance in children
- Driving impairment in adults 6
An epidemiologic study found drivers responsible for fatal accidents were 1.5 times more likely to be taking first-generation antihistamines than drivers killed but not responsible for accidents 6.
Anticholinergic Effects
Hydroxyzine can cause:
- Dry mouth and eyes
- Constipation
- Inhibition of micturition
- Increased risk for narrow-angle glaucoma 6
Special Populations
- Elderly: More sensitive to psychomotor impairment, increased risk for falls, fractures, subdural hematomas, and more susceptible to anticholinergic effects 6
- Children: May impair learning and school performance 6
- Pregnancy: Contraindicated during early pregnancy 2
Alternatives to Consider
- For anxiety: SSRIs, SNRIs, or buspirone may be safer alternatives 2
- For insomnia: Short-acting benzodiazepine receptor agonists or ramelteon may be preferred 2
- For allergic conditions: Second-generation antihistamines (cetirizine, loratadine) with less CNS penetration are safer alternatives 2
Clinical Pearls
Avoid AM/PM dosing regimens: First-generation antihistamines like hydroxyzine have prolonged half-lives and can cause significant daytime drowsiness even when dosed only at bedtime 6.
Monitor for occupational hazards: Workers taking hydroxyzine may exhibit impaired work performance and productivity and are more likely to be involved in occupational accidents 6.
Beware of drug interactions: Concomitant use with other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) may further enhance performance impairment 6.
Inform patients about alternatives: Before prescribing hydroxyzine, ensure patients understand both the potential for adverse effects and the availability of alternative antihistamines with fewer adverse effects 6.
Consider for nighttime pruritus: First-generation antihistamines like hydroxyzine may be considered based on their sedative properties in patients who suffer from pruritus during nighttime 6.