Hydroxyzine is intended for short-term use only (less than 4 months) when used to treat anxiety. Using hydroxyzine long-term would be considered an off-label use for the drug because there are no studies looking at the long-term effects of hydroxyzine. Some research suggests a link between long-term use of medications with anticholinergic properties, such as hydroxyzine, and dementia, particularly in older adults. Brain fog has also been reported with long-term use.

Other conditions that hydroxyzine may be prescribed for, such as itchy skin due to an allergy, hives, dermatitis, or eczema, or as a sedative before surgery or other procedures, are generally short-lived and there is no need to prescribe hydroxyzine long-term.