What is the best antihistamine for anxiety? A look at hydroxyzine and other options

October 6, 2025 •

3 min read

With more than 30% of adults experiencing an anxiety disorder at some point in their lives, many seek different treatment options. The question, 'What is the best antihistamine for anxiety?', has a clear answer, but it's important to understand the role these medications play in symptom relief, particularly as a short-term solution.

Quick Summary

Hydroxyzine is the only FDA-approved antihistamine for short-term anxiety relief. While it's a fast-acting option, it is not for long-term use. Other over-the-counter options like Benadryl are not recommended for managing anxiety symptoms.

Key Points

Hydroxyzine is the best antihistamine for anxiety: It is the only antihistamine that is specifically FDA-approved and widely studied for the short-term treatment of anxiety.
Not a long-term solution: Hydroxyzine is intended for short-term, as-needed anxiety relief, typically no longer than four months, because tolerance can develop.
Other OTC antihistamines are not recommended: Medications like Benadryl (diphenhydramine) and Unisom (doxylamine) are not approved for anxiety and are less effective and potentially riskier for this purpose.
Drowsiness is a common side effect: Hydroxyzine and other first-generation antihistamines cause sedation, which can help with anxiety-related insomnia but also impairs daytime alertness.
Consult a healthcare provider: It is essential to speak with a doctor before using any antihistamine for anxiety, as it may not be appropriate for everyone and can interact with other medications.
Not habit-forming like benzodiazepines: Hydroxyzine is not a controlled substance and does not carry the same risk of dependence as benzodiazepines.
Consider other treatment options: For chronic anxiety, SSRIs, SNRIs, and therapy are more effective long-term solutions, and hydroxyzine may be used temporarily alongside them.

Understanding Antihistamines for Anxiety

Antihistamines are primarily known for treating allergic reactions by blocking histamine. They are categorized into first-generation (sedating) and second-generation (non-drowsy) types. While second-generation antihistamines are typically preferred for allergies, first-generation antihistamines can cross the blood-brain barrier and cause drowsiness, leading some to explore their use for temporary anxiety relief. This calming effect can offer symptomatic relief for acute anxiety, but it doesn't address the underlying causes. Sedation can make first-generation antihistamines unsuitable for daytime use. It is crucial to distinguish between medically prescribed antihistamine use for anxiety and unadvised use of over-the-counter products.

Hydroxyzine: The Prescription Antihistamine for Anxiety

Hydroxyzine is the only antihistamine specifically approved by the FDA for treating anxiety. Available by prescription as Vistaril (pamoate) and Atarax (hydrochloride), it's used for anxiety and tension. Its anxiolytic effects are thought to be due to blocking histamine and increasing serotonin levels in the brain. Unlike benzodiazepines, hydroxyzine is not habit-forming, making it a safer short-term option. However, its long-term effectiveness for anxiety disorders isn't established, and tolerance can develop.

Over-the-Counter (OTC) Antihistamines for Anxiety

Using OTC antihistamines like diphenhydramine (Benadryl) or doxylamine (Unisom) for anxiety is not recommended. They are not FDA-approved for anxiety and lack the same mechanism of action as hydroxyzine. Their sedative effects can cause unwanted side effects like drowsiness and cognitive impairment, and they can even paradoxically worsen anxiety in some cases. Non-drowsy second-generation antihistamines are also not effective for anxiety as they do not provide a sedative effect.

Antihistamine Use: Potential Side Effects and Safety

Using any antihistamine for anxiety requires awareness of potential side effects and safety considerations, highlighting the importance of medical supervision.

Common Side Effects:

Drowsiness
Dry mouth
Dizziness
Constipation

Serious Side Effects:

Heart rhythm changes (rare, especially with hydroxyzine)
Cognitive issues with long-term use
Urinary retention

Drug Interactions:

Increased sedation with alcohol
Interactions with other medications like CNS depressants and some antidepressants

Hydroxyzine vs. OTC Antihistamines for Anxiety: A Comparison


Feature	Hydroxyzine (Vistaril/Atarax)	OTC Antihistamines (e.g., Benadryl)
FDA Approval for Anxiety	Yes.	No.
Availability	Prescription only.	Over-the-counter.
Primary Purpose	Short-term anxiety relief.	Allergy relief; sedation is a side effect.
Mechanism for Anxiety	Blocks histamine and increases serotonin.	Primarily relies on sedative effects.
Potential for Dependence	No.	Low risk.
Duration of Action	Longer half-life.	Shorter half-life.
Safety Profile	Generally well-tolerated short-term under medical supervision; risks in elderly.	Not recommended for anxiety due to limited efficacy and safety concerns; risks with long-term use.

Best Practices for Taking an Antihistamine for Anxiety

If an antihistamine is part of your anxiety treatment, follow these guidelines:

Consult a physician before use.
Follow the prescribed dosage for hydroxyzine.
Use hydroxyzine as needed for acute episodes rather than continuously.
Avoid driving or operating machinery due to drowsiness.
Avoid alcohol and inform your doctor of all other medications.
Monitor for side effects and contact your doctor if unusual symptoms occur.

Conclusion: When is an Antihistamine the Right Choice?

For the question, 'What is the best antihistamine for anxiety?', hydroxyzine is the recommended option due to its FDA approval and studies for short-term anxiety relief. However, it is a short-term solution and not a primary treatment for anxiety disorders. OTC antihistamines are not recommended for anxiety. For chronic or severe anxiety, long-term treatments like SSRIs, SNRIs, and cognitive behavioral therapy (CBT) are more effective. Hydroxyzine may be used as a temporary measure alongside these treatments. Always consult a healthcare professional to determine the best treatment plan for your needs.

For more information on anxiety and its treatment options, visit the National Alliance on Mental Illness (NAMI) website(https://www.nami.org/about-mental-illness/treatments/mental-health-medications/types-of-medication/hydroxyzine-vistaril/).

Frequently Asked Questions

No, it is not recommended to take Benadryl (diphenhydramine) for anxiety. It is not FDA-approved for anxiety and has limited efficacy, and its sedative effects can cause unwanted side effects like impaired cognitive function.

No, unlike some other anti-anxiety medications such as benzodiazepines, hydroxyzine is not considered habit-forming or addictive. It is not a controlled substance.

Hydroxyzine is intended for short-term use, typically for acute episodes of anxiety. The manufacturer's studies have not assessed its effectiveness for longer than four months, as tolerance can develop.

No, non-drowsy antihistamines like Claritin (loratadine) and Zyrtec (cetirizine) do not significantly cross the blood-brain barrier and therefore do not provide a calming or sedative effect for anxiety relief.

Common side effects include drowsiness, dry mouth, blurred vision, dizziness, and constipation. These effects can impact daily activities like driving and should be monitored.

Hydroxyzine should be used with caution in older adults. They are more susceptible to side effects like extreme sedation, confusion, and urinary issues. A lower dose or alternative treatment is often recommended.

Yes, hydroxyzine can interact with many other medications, including alcohol, certain antidepressants, heart medications, and other sedatives. It is essential to discuss all medications and supplements with a doctor to avoid dangerous interactions.