From the Guidelines
Long-term use of hydroxyzine is associated with significant adverse effects, including anticholinergic effects, cognitive impairment, and QT interval prolongation, and its use should be avoided in older adults and monitored closely in all patients, as recommended by the 2019 Beers Criteria 1.
Adverse Effects of Hydroxyzine
The adverse effects of long-term hydroxyzine use can be categorized into several key areas, including:
- Anticholinergic effects, such as confusion, constipation, urinary retention, and blurred vision, which are particularly concerning in elderly patients 1
- Cognitive impairment, including memory problems and decreased concentration, which can impact daily functioning and quality of life
- QT interval prolongation, which can increase the risk of serious cardiac arrhythmias, especially in patients with pre-existing heart conditions or those taking other QT-prolonging medications
- Tolerance and dependence, which can lead to increased dosages and withdrawal symptoms when attempting to stop the medication
- Masking of underlying conditions, which can delay diagnosis and treatment of other health issues
Recommendations for Use
Given the potential risks associated with long-term hydroxyzine use, it is recommended that patients use the lowest effective dose for the shortest possible duration, and that healthcare providers closely monitor patients for adverse effects and evaluate the need for continued use 1. Regular follow-up appointments can help identify potential issues early on and ensure that patients receive appropriate care. Additionally, alternative treatment options should be considered, especially for older adults, to minimize the risk of adverse effects and optimize outcomes.
From the FDA Drug Label
THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, NON-NARCOTIC ANALGESICS AND BARBITURATES. QT Prolongation/Torsade de Pointes (TdP): Cases of QT prolongation and Torsade de Pointes have been reported during post-marketing use of hydroxyzine. Since drowsiness may occur with use of this drug, patients should be warned of this possibility and cautioned against driving a car or operating dangerous machinery while taking hydroxyzine. Acute Generalized Exanthematous Pustulosis (AGEP) Hydroxyzine may rarely cause acute generalized exanthematous pustulosis (AGEP), a serious skin reaction characterized by fever and numerous small, superficial, non-follicular, sterile pustules, arising within large areas of edematous erythema Skin and Appendages: Oral hydroxyzine hydrochloride is associated with Acute Generalized Exanthematous Pustulosis (AGEP) and fixed drug eruptions in post marketing reports. Side effects reported with the administration of hydroxyzine hydrochloride are usually mild and transitory in nature. Anticholinergic: Dry mouth Central Nervous System: Drowsiness is usually transitory and may disappear in a few days of continued therapy or upon reduction of dose. Involuntary motor activity including rare instances of tremor and convulsions have been reported, usually with doses considerably higher than those recommended. In post-marketing experience, the following additional undesirable effects have been reported: Cardiac System: QT prolongation, Torsade de Pointes. Body as a Whole: Allergic reaction. Nervous System: Headache. Psychiatric: Hallucination. Skin and Appendages: Pruritus, rash, urticaria.
The adverse effects of long-term hydroxyzine use include:
- Drowsiness which may be transitory
- QT prolongation and Torsade de Pointes
- Acute Generalized Exanthematous Pustulosis (AGEP), a serious skin reaction
- Anticholinergic effects such as dry mouth
- Involuntary motor activity including tremor and convulsions
- Allergic reactions
- Headache
- Hallucination
- Pruritus, rash, and urticaria 2 2
From the Research
Adverse Effects of Long-Term Hydroxyzine Use
The adverse effects of long-term hydroxyzine use can be significant. Some of the reported side effects include:
- Drowsiness or sleepiness, which was found to be more common with hydroxyzine compared to other anxiolytic agents 3
- QT prolongation, which can lead to torsade de pointes (TdP), a potentially life-threatening arrhythmia 4
- Sedation, which can be problematic in elderly patients or those with a history of substance abuse 5, 6
- Cognitive impairment, including attention and memory deficits, although some studies suggest that hydroxyzine may preserve memory and attention better than other sedative medications 5
Comparison to Other Medications
Hydroxyzine has been compared to other medications, including benzodiazepines and buspirone, in terms of its efficacy and safety. Some studies suggest that hydroxyzine is equivalent to these medications in terms of efficacy, but may have a more favorable side effect profile 3, 7. However, other studies have raised concerns about the potential for hydroxyzine to cause QT prolongation and TdP, particularly when used in combination with other medications or in patients with underlying heart conditions 4.
Special Considerations
When using hydroxyzine, particularly for long-term treatment, it is essential to consider the following:
- Monitor electrolyte levels and perform regular electrocardiograms to minimize the risk of QT prolongation and TdP 4
- Use the lowest effective dose and avoid drug interactions to reduce the risk of adverse effects 4
- Exercise caution in patients with underlying repolarization abnormalities or a history of TdP 4
- Consider alternative medications or treatment options, particularly in patients who are at high risk for adverse effects or who have a history of substance abuse 6, 7