Hydroxyzine is a first generation histamine (H1) antagonist that’s been on the market since the 1950’s.1 Its mechanisms of action are unique. Not only does it compete with histamine for H1 receptor sites in the GI tract, blood vessels, and respiratory tract, but it also it exhibits activity at muscarinic, serotonergic, and dopaminergic receptors in various parts of the brain, which may explain its anxiolytic effect.2 Hydroxyzine is available in two different salt forms, hydroxyzine hydrochloride (HCl) (commonly known as Atarax) and hydroxyzine pamoate (commonly known as Vistaril).
It’s often believed that Atarax is better for treating itching and Vistaril is better for treating anxiety or difficulty sleeping. You may have even heard that Vistaril is more lipophilic and, thus, more likely to cross the blood brain barrier. However, hydroxyzine, regardless of which salt preparation it comes from, readily penetrates the CNS and partitions into brain tissue.3
While hydroxyzine is available in two different salts, there’s no evidence to suggest a material difference between the two or that utilization of one over the other is more advantageous.4 So, where do these notions come from?
These (mis)perceptions appear to be based on tradition and anecdote. For one thing, not all products branded as Vistaril are the pamoate salt form.4 The injectable formulation, hydroxyzine HCl, was initially marketed as Vistaril.4 Since the injectable provides a quicker onset of action compared to oral administration, it’s preferred when rapid sedation is needed.2,4 This might help explain how Vistaril became known as the agent of choice for anxiety or sleep.4 When the hydroxyzine pamoate products came out, they were also marketed as Vistaril; and the reputation of being a remedy for anxiety or sleep likely followed.4
Hydroxyzine HCl and hydroxyzine pamoate have the same mechanisms of action, dosing recommendations, and labeled indications (anxiety, management of pruritus due to allergic conditions and histamine mediated causes, and as a sedative when used as premedication to, or following, general anesthesia). 2,5,6
Seemingly the only material difference between the two is dosage form and cost. Hydroxyzine HCl is available as tablets, syrup and solution for intramuscular injection, while hydroxyzine pamoate is only available in capsule form.2 In the hospice setting, hydroxyzine HCl tablets and hydroxyzine pamoate capsules are the most commonly used dosage forms. However, the two vary significantly in price. Pricing for commonly used hydroxyzine products and strengths can be seen in Table 1. Generally speaking, when the desired dose is 25 or 50mg, hydroxyzine pamoate capsules would be the preferred agent from a cost perspective.
Table 1. Hydroxyzine Pricing7
Since there’s no clinical advantage of either formulation over the other, the choice really boils down to preferred dosage form (e.g., tablets or capsules) and cost. The old adage that Atarax is for itch and Vistaril is for anxiety and sleep is nothing more than a myth that has been passed down among generations of practitioners over time.
John Corrigan, PharmD
Clinical Pharmacist, OnePoint Patient Care
- Guaiana G, Barbui C, Cipriani A. Hydroxyzine for Generalised Anxiety Disorder. Cochrane Database of Systematic Reviews. 2010; 12. Art. No.:CD006815. doi:1002/14651858.CD006815.pub.2
- Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Accessed May 20, 2021.
- Chen C. Physicochemical, Pharmacological and Pharmacokinetic Properties of the Zwiterionic Antihistamines Cetirizine and Levocetirizine. Current Medicinal Chemistry. 2008;15(21): 2173-2191. doi: 2174/092986708785747625
- Atarax is for Itch and Vistaril is for Anxiety. Pharmacist’s Letter. 2021. Accessed May 20, 2021. https://pharmacist.therapeuticresearch.com/Content/Articles/PL/2005/Dec/i-Atarax-i-is-for-itch-and-i-Vistaril-i-is-for-anxiety
- Hydroxyzine Hydrochloride. Package Insert. Teva Pharmaceuticals USA Inc.; 2016. Accessed May 19, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80309ec1-e5d5-4454-b8ce-67d7e6805e44
- Hydroxyzine Pamoate. Package Insert. Amneal Pharmaceuticals of New York LLC; 2021. Accessed May 19, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bc82aaaf-30c7-4afe-a908-d138ea1268ef
- AmerisourceBergen. Accessed May 21, 2021.