Hydroxyzine For Anxiety: Practical Tips From A Clinician
Written By Kobi Nathan, Pharm.D., M.Ed., CDP, BCGP, AGSF
Sleep Disorders
August 13, 2023

Hydroxyzine for anxiety

Anxiety disorders are the most common mental illnesses afflicting people in the United States.

Approximately 40 million people, accounting for 19% of the U.S. population, suffer from this highly treatable medical problem.

Even though this illness can be effectively managed, only about 37% of sufferers seek out treatment.

People with anxiety are six times more likely to be hospitalized than those without it.

This medical condition arises from not just one issue but a complex mix of various risk factors negatively affecting the individual.

These risk factors may include life events, brain chemicals, an individual’s personality, and how they respond to stressors in their lives, and importantly, genetic factors may play a big role in the genesis of anxiety disorders.

Symptoms of anxiety include:

  • Excessive worrying (rumination)
  • Difficulty with concentrating on tasks
  • Sleep disturbances (trouble falling and staying asleep)
  • Feeling irritable
  • Excessive nervousness
  • Excessive fearfulness

Anxiety sufferers also tend to have accompanying depression.

Nearly half of all people with depression are also diagnosed with Anxiety.

There are different types of anxiety disorders.

The table below provides an overview of each disorder, including important facts and figures related to each one.

Anxiety Disorder Types - Facts & Figures

Disorder TypeStatisticsImportant Facts
Generalized Anxiety Disorder (GAD)Affects 6.8 million adults or 3.1% of the U.S. population, only 43.2% are receiving treatmentWomen are twice as likely to be affected as men. GAD often co-occurs with major depression.
Panic Disorder (PD)Affects 6 million adults or 2.7% of the U.S. populationWomen are twice as likely to be affected as men
Social Anxiety Disorder (SAD)Affects 15 million adults or 7.1% of the U.S. populationEqually common among men and women; begins around age 13. 36% of people with social anxiety disorder report - experiencing symptoms for 10 or more years before seeking help.
Specific PhobiasAffect 19.3 million adults or 9.1% of the U.S. populationWomen are twice as likely to be affected than men. Symptoms typically begin in childhood; the average age of onset is 7 years old.
Obsessive-Compulsive Disorder (OCD)Affects 2.5 million adults or 1.2% of the U.S. population. Women are 3x more likely to be affected than men.Average age of onset is 19, with 25% of cases occurring by age 14. One-third of affected adults first experienced symptoms in childhood.
Post-traumatic Stress Disorder (PTSD)Affects 7.7 million adults or 3.6% of the U.S. population. Women are 5x more likely to be affected than men.Rape is most likely trigger of PTSD: 65% of men and 45.9% of women who are raped will develop the disorder.
- Childhood sexual abuse is a strong predictor of the lifetime likelihood of developing PTSD.
Data Source and Credit: https://adaa.org/understanding-anxiety/facts-statistics#Facts%20and%20Statistics. Accessed August 29, 2022.

In addition to Depression, several other disorders tend to co-occur with Anxiety.

The following are some of them:

Anxiety in older adults

Among all of the anxiety disorders mentioned, Generalized Anxiety Disorder (GAD) is the most common among older adults.

Since falls and resulting fractures or surgeries are a known problem among frail older adults, deep, paralyzing anxiety may envelop our older loved ones.

Anxiety sets in once they fall and hurt themselves, and older adults may be very apprehensive and hesitant about putting themselves in similar situations, attempting to prevent future falls and hospitalizations proactively.

The problem with this approach is that the more our older loved ones limit their mobility, the weaker they become due to lack of exercise and conditioning.

This practice becomes a vicious cycle that inevitably leads to more anxiety and negative health-related outcomes for our loved ones.

I talk about this in my article on Geriatric Syndromes.

So, anxiety and depression must be addressed and treated in older adults because the consequences can harm our loved ones.

Treating anxiety with medications in the elderly comes with challenges, and we must tread carefully.

Choosing the right class of prescription drugs is very important.

Inappropriate prescribing can lead to the dangers we want to avoid in our older adults.

I will explain what I mean by this statement later in this article when I discuss using hydroxyzine in older adults.

Treatment options for anxiety

Treatment Options are plentiful for anxiety and may include:

  • Non-pharmacological Management (Counseling sessions with therapists, Cognitive Behavioral Therapy, grounding techniques, etc)
  • Pharmacological Management (Anxiety medications – SSRIs, Buspirone, benzodiazepines, hydroxyzine, etc)
  • Complementary and alternative treatment (Meditation, Acupuncture, Yoga, etc)
  • Transcranial Magnetic Stimulation (TMS)

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What is Hydroxyzine? (pronounced hye-DROKS-i-zeen)

Hydroxyzine (pronounced hye-DROKS-i-zeen) is a first-generation antihistamine prescription medication (not available over the counter).

It was created in 1955 and is currently still in use.

Hydroxyzine is not a controlled drug.

It is used to treat allergic conditions such as:

  • Pruritis (itching)
  • Urticaria (also known as hives or welts – raised, itchy rash on the skin)
    Hives

    Urticaria (Hives)

  • Dermatoses (any skin irregularity or lesion)

Interesting fact: In breaking it down, the body converts it to the active metabolite cetirizine, more commonly known as “Zyrtec,” the common OTC antihistamine sold in stores!

Cetirizine is responsible for hydroxyzine’s antihistamine effects on the histamine receptors.

Hydroxyzine is also used to treat anxiety symptoms – more on the mechanism by which this drug exerts its calming effect to treat this condition will be discussed later in this article.

Atarax vs Vistaril: Is one better than the other?

There are two different formulations of hydroxyzine – hydroxyzine hydrochloride (HCL), also known as Atarax, and hydroxyzine pamoate, commonly known as Vistaril.

hydrochloride

Hydroxyzine hydrochloride (Atarax)

Hydroxyzine Pamoate

Hydroxyzine Pamoate (Vistaril)

Of the two brand names, Atarax has been discontinued by its manufacturer.

The decision, by all accounts, was strictly due to strategic business reasons.

There were no specific safety or efficacy reasons for the drug’s removal from the market.

 

The generic version of Atarax, hydroxyzine HCL is still being marketed in the United States.

Hydroxyzine pamoate is available as a brand and generic medication.

Here are the available dosage forms for hydroxyzine currently available in the U.S.:

Available Hydroxyzine Formulations

Brand/GenericAvailable Dosage Form
Vistaril/hydroxyzine pamoateCapsule: 25 mg, 50 mg
Liquid: 25 mg/5 mL suspension
Brand name Atarax discontinued/hydroxyzine hydrochlorideTablet: 10 mg, 25 mg, 50 mg
Liquid: 10 mg/5mL suspension
Injection: 25 mg/mL, 50 mg/mL

There is confusion about the indication for each formulation.

Some claim that Atarax (hydroxyzine hydrochloride) is better for managing itchy skin, and Vistaril (hydroxyzine pamoate) is better suited to manage anxiety or insomnia due to its sedating properties.

These contentions are actually myths. There’s no material difference between the two drug formulations; they penetrate the blood-brain barrier equally and enter the brain just as readily.

The only seemingly benign difference between both drug formulations seems to be the dosage form they come in:

Hydroxyzine pamoate comes in capsule and oral suspension form, and hydroxyzine hydrochloride comes in more options, specifically tablets, syrup, and an intramuscular injection solution.

Regardless of the formulation, hydroxyzine is very inexpensive.

Here’s the cost breakdown between both formulations, according to Good Rx (current as of 8/30/22):

 

Good Rx Prices For Hydroxyzine Formulations with Free Coupon

Drug FormulationPharmacyPrice for 25 mg, quantity = 60
Hydroxyzine PamoateWalmart
CVS
Rite Aid
Stop n Shop
Kroger
$12.78
$10.34
$3.28
$9.67
$7.92
Hydroxyzine HydrochlorideWalmart
CVS
Rite Aid
Stop n Shop
Kroger
$7.72
$12.79
$5.18
$12.38
$13.97
As you can see, the price difference between both drug formulations is very minimal.
Source: goodrx.com

 

Hydroxyzine for anxiety

Besides its antihistamine properties, clinical and research evidence suggests hydroxyzine also possesses anti-anxiety properties.

Hydroxyzine has the most clinical evidence for treating general anxiety.

A clinical review published in 2010 concluded that hydroxyzine worked better than a placebo and was comparable to benzodiazepines and buspirone.

Unlike first-generation antihistamines, hydroxyzine also works on other important brain chemicals responsible for mood regulation.

It is an antagonist of the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the alpha1-adrenergic receptor.

Numerous studies have shown that serotonin 5-HT2A receptor blockade has antipsychotic, anti-anxiety, and anti-depression properties.

Serotonin is a chemical brain messenger that carries signals between nerve cells in your brain and throughout your body.

It plays an important role in regulating mood, digestion, sleep, wound healing, bone health, blood clotting, and sexual desire.

Specifically, it increases serotonin levels in the brain by blocking its reabsorption at the receptor sites in the brain’s nerves.

How long does it take for hydroxyzine to start working?

Hydroxyzine is rapidly absorbed from the GI tract once it is taken and works very fast – the onset of action occurs between 15 and 60 minutes of taking the drug, and its duration of action (how long it exerts its intended pharmacological effect) is between 4 to 6 hours.

The maximum effect will be felt around 2 hours after taking the medication.

How long does hydroxyzine stay in your system?

Hydroxyzine stays in your system for 100 hours since the last dose.

However, its therapeutic effect will wear off before this time.

Its half-life, the time required for its blood concentration to be reduced to 50% of its original value, is around 20 hours.

For any medication to be eliminated from the body, it takes about 5 half-lives.

So, doing the math, hydroxyzine’s half-life is 20 hours x 5 = 100 hours.

 

How to take hydroxyzine for anxiety?

Hydroxyzine may be taken with or without food. If you are prone to stomach upsets, take the medication with food.

The medication may be taken regularly as a standing regimen or as needed.

If you miss a dose, take it as soon as you remember. DO NOT double-dose!

If too much time has passed since your last dose, skip the missed dose and take the next dose at the regularly scheduled time.

That said, medications like hydroxyzine are not meant to be taken long-term for anxiety.

If used to reduce anxiety, most providers will use it as a bridge while a selective serotonin reuptake inhibitor (Lexapro, Zoloft, etc.) is initiated and takes effect over a few weeks.

Hydroxyzine dosing

  • Hydroxyzine for anxiety: 50 mg to 100 mg four times daily
  • Itchy skin (pruritus): 25 mg three or four times daily
  • Premedication for general anesthesia: 50 mg to 100 mg dose before the procedure

**Dosage must be adjusted according to the patient’s response and tolerability, or if they have kidney or liver problems

What are the side effects of hydroxyzine?

Using hydroxyzine for anxiety is generally safe and effective.

Side effects may be mild and transient.

When taken as prescribed, serious side effects are rare.

Can you overdose on hydroxyzine?

Hydroxyzine overdose occurs when an individual takes more than the prescribed dose, intentionally or unintentionally.

To manage hydroxyzine overdose, seek immediate medical attention!

Your doctor may induce vomiting and use a gastric lavage to wash out your stomach contents.

Apart from that, treatment is centered around supportive and symptomatic care.

Hydroxyzine overdose side effects

The tell-tale, classic sign of hydroxyzine overdose is dilated pupils.

This is directly a result of hydroxyzine-induced anticholinergic toxicity.

Here are some other symptoms of overdose:

  • Some people have reported fixed drug eruptions (development of one or more circular or oval red patches on the skin)
  • Shortness of breath
  • Ringing in the ears (tinnitus)
  • Blurred vision/Dry eyes
  • Urinary difficulties
  • Nausea and Vomiting
  • Dry mouth ( classic and common anticholinergic reaction)
  • Drowsiness (hypersedation seen in overdose situations)
  • Tremors and involuntary motor movements
  • Convulsions (rare, usually seen with higher doses)
  • Headaches
  • Hallucinations
  • Skin itchiness, rash, and redness (flushed skin)
  • Irregular heartbeat
  • Possible allergic reaction (rare)

If you experience any of the symptoms above, call your doctor immediately or go to emergency care quickly.

 

Hydroxyzine drug interactions

Many medications can interact with hydroxyzine.

Any central nervous system depressing drugs such as opioids, benzodiazepines, and sleep agents (Ambien, Lunesta, etc.) can increase sedation, cognitive impairment, and risk of falls and hospitalization.

Your healthcare provider must provide oversight with all your medications and will adjust your doses accordingly.

Alcohol, due to its sedative properties, can also worsen the effects of hydroxyzine.

 

Is it safe for the elderly to take hydroxyzine?

Some suggest hydroxyzine does not negatively affect older adults as much as other first-generation antihistamines, such as Benadryl (diphenhydramine).

They contend that its mechanism of action does not result in high anticholinergic activity (anticholinergic drugs are a big no-no for older adults).

I would argue that it does.

My reasoning is that it still has anticholinergic properties, and the fact that it causes sedation is a big risk factor for falls, impaired cognition, and worsening of underlying cognitive impairment.

The liver breaks down hydroxyzine into the active metabolite cetirizine (Zyrtec), and approximately 70% of this by-product is cleared unchanged by the kidneys.

If the drug is not cleared quickly enough, it accumulates in the body, causing extra sedation, cognitive impairment, and increasing the risk of falls, fractures, and premature death.

Older adults’ kidney function decreases over time, and many have chronic kidney disease.

Taking hydroxyzine can be dangerous in this setting as it will accumulate in their bodies.

Another reason is that hydroxyzine acts as a subcortical CNS depressant.

The subcortical region of the brain is responsible for the more basal and vital functioning of the brain, such as memory, emotion, pleasure, information processing speed, the ability to respond quickly to emerging threats and changes, and hormone synthesis.

Hydroxyzine’s ability to suppress these functions is why it possesses anti-anxiety effects.

There is also a negative impact of hydroxyzine’s action on the subcortical region of the brain – as stated above, memory is affected, and the ability to respond to immediate threats while driving, for example, may end up harming our older loved ones.

The manufacturer of Vistaril states in the package insert that sufficient numbers of participants aged 65 and over were not included in the clinical studies.

As such, they cannot clearly state that there may be a difference in response to the drug between younger and older patients.

With regard to starting doses in older adults, I will always defer to my geriatric mantra: Start Low, Go Slow! 

We must always be mindful that our older adults have chronic diseases, compromised liver and kidney function, and are on other maintenance medications that could interact with hydroxyzine.

If you are an older adult taking it as prescribed, don’t stop taking hydroxyzine simply because of what you read here.

ALWAYS treat what you read online as guidance, and talk to your doctor before making any medication-related decisions.

Do not take it more often or for a longer time than your doctor ordered it.

In other words, you should follow professional medical advice at all times.

Hydroxyzine precautions

People with the following medical problems should exercise caution and talk to their healthcare provider before starting hydroxyzine:

  • Past or current electrolyte imbalance (sodium, potassium, magnesium).
  • History of heart attack.
  • Heart disease.
  • Heart failure.
  • Heart rhythm problems or family history of heart problems (eg, long QT syndrome, slow heartbeat) – Can be caused by hydroxyzine or worsen underlying problems – use with caution.
  • Heart rhythm problem (prolonged QT interval) – Do not use in patients with this condition.
  • Skin problems—Use with caution. Conditions can be worsened.

Hydroxyzine use during pregnancy

Hydroxyzine is contraindicated during the first trimester of pregnancy due to the risk of fetal defects.

Out of an abundance of caution, hydroxyzine should also not be used during the second and third trimesters.

Hydroxyzine FAQs:

What is hydroxyzine used for?

Hydroxyzine is typically used to treat anxiety, skin itch, allergic symptoms, and sleep problems.

Is hydroxyzine habit-forming?

No, it is not a controlled substance or a narcotic.

Unlike other anti-anxiety medications, discontinuation has no withdrawal symptoms and can be stopped immediately.

Does hydroxyzine cause weight gain?

In clinical studies, weight gain was not reported as a side effect of hydroxyzine.

How fast does hydroxyzine work to help you fall asleep?

You start to feel drowsy in as little as 15-30 minutes.

Can I take hydroxyzine long-term?

It is not meant for long-term use, especially as an anti-anxiety medication.

Better options are Selective serotonin reuptake inhibitors such as Lexapro and Zoloft.

Why was Atarax discontinued?

For business reasons. No concerns were noted for safety or efficacy.

Is there a difference between hydroxyzine pamoate (Atarax) and hydrochloride (Vistaril)?

No. Both formulations work the same way.

Is hydroxyzine excreted in breast milk?

It is not known if hydroxyzine is excreted in human breast milk.

As a precaution, infants should not be breastfed while the mother is taking hydroxyzine.

 

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