Long-Term Effects of Vistaril (Hydroxyzine)
Hydroxyzine should be avoided for long-term use due to significant risks of persistent cognitive impairment, anticholinergic complications, and increased falls/fractures, particularly in older adults, with guideline consensus recommending it only for short-term management.
Central Nervous System Impairment
Long-term hydroxyzine use causes persistent cognitive and psychomotor deficits that extend beyond subjective awareness of sedation 1:
- Performance impairment persists longer than plasma drug levels due to prolonged half-lives of hydroxyzine and its active metabolites, meaning cognitive deficits continue even after the drug feels like it has "worn off" 1
- Drivers taking hydroxyzine are 1.5 times more likely to be responsible for fatal automobile accidents compared to non-users 1
- Even bedtime-only dosing causes significant daytime drowsiness, decreased alertness, and performance impairment the following day 1
- Workers experience impaired work performance, reduced productivity, and increased occupational accident risk 1
- Children may experience impaired learning and school performance 1
Anticholinergic Toxicity
Chronic anticholinergic exposure from hydroxyzine leads to cumulative adverse effects 2, 1:
- CNS impairment including delirium and slowed comprehension 2
- Impaired vision and increased risk for narrow-angle glaucoma provocation 1
- Urinary retention and inhibition of micturition 1
- Chronic constipation 1
- Dry eyes and dry mouth 1
Geriatric Complications
Hydroxyzine is specifically identified in polypharmacy management guidelines as a medication to avoid in older patients 2:
- Older adults demonstrate heightened sensitivity to psychomotor impairment from hydroxyzine 1
- Increased risk for sedation, falls, and injurious fractures 2, 1
- Anticholinergic burden contributes to cognitive decline and delirium risk 2
- The Mayo Clinic guidelines explicitly list hydroxyzine among antihistamines causing "CNS impairment: delirium, slowed comprehension; impairs vision, urine retention, constipation, sedating, falling" 2
Special Population Risks
Pregnancy and Neonatal Effects
- Hydroxyzine is contraindicated during early pregnancy 1
- Maternal use can cause neonatal withdrawal syndrome with tremors, irritability, hyperactivity, jitteriness, shrill cry, myoclonic jerks, hypotonia, increased respiratory and heart rates, feeding problems, and clonic movements 1
- Withdrawal symptoms in neonates may persist up to 5 weeks even with treatment 1
Renal and Hepatic Impairment
- Dose must be halved in moderate renal impairment and avoided entirely in severe renal impairment 1
- Should be avoided in severe liver disease due to inappropriate sedating effects 1
Drug Interaction Concerns
Concomitant use with other CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) further enhances performance impairment 1. This creates compounding cognitive deficits that are particularly dangerous in real-world settings.
Clinical Context: Short-Term Use Only
While hydroxyzine demonstrates efficacy for generalized anxiety disorder in short-term trials (4 weeks), with superiority over placebo beginning in the first week 3, 4, 5, there is no evidence supporting long-term efficacy or safety. The clinical trials establishing hydroxyzine's anxiolytic effects were limited to 4-week durations 5, and the drug's side effect profile makes extended use problematic.
Common pitfall: Prescribers may continue hydroxyzine indefinitely after initiating it for acute anxiety or insomnia, failing to recognize that the cognitive impairment and anticholinergic burden accumulate over time while tolerance to therapeutic effects may develop.
Alternative Considerations
For delirium management specifically, recent evidence suggests hydroxyzine may have a role in acute settings 6, but this does not translate to chronic use recommendations. The ESMO guidelines note that hydroxyzine is listed among medications that should be used short-term only for symptom management 2.