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While there are reports of the "hallucinogenic" or "hypnotic" properties of hydroxyzine, several clinical data trials have not reported such side effects from the sole consumption of hydroxyzine, but rather, have described its overall calming effect described through the stimulation of areas within the formatio reticularis.The hallucinogenic or hypnotic properties have been described as being an additional effect from overall central nervous system suppression by other CNS agents, such as lithium or ethanol.

The second-generation antihistamine cetirizine is in fact one of the metabolites of hydroxyzine produced in the human body.Unlike hydroxyzine, cetirizine is not reported to appreciably cross the blood-brain barrier, but it has been reported to be associated with dystonic reactions as well as sedation.In 2015, the European Medicines Agency (EMA) announced a small but definite risk of QT prolongation associated with the use of hydroxyzine.This side effect is more likely to occur in people with pre-existing cardiac disease, or with the use of other medicines known to prolong the QT interval.Today it is used primarily for the symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested.

Other drugs related to hydroxyzine are cyclizine, buclizine, and meclizine, and they share all or most of the benefits, indications, contraindications, cautions, and side effects of hydroxyzine.

Hydroxyzine has also been used to potentiate the analgesia of opioids and to alleviate some of their side effects, such as itching, nausea, and vomiting.

Due to its antagonistic effects on several receptor systems in the brain, hydroxyzine also has anxiolytic, antiobsessive, and antipsychotic activity.

Unlike many other first-generation antihistamines, hydroxyzine has very low affinity for the muscarinic acetylcholine receptors, and in accordance, has low or no propensity for producing anticholinergic side effects.

Hydroxyzine can be administered orally or via intramuscular injection.

Hydroxyzine is prescribed when the onset of an organic disease state manifests through anxiety, as generalized anxiety disorder, or in other more serious cases as psychoneurosis, and is therefore prescribed as a means of regulating normal function.