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Hydroxyzine Tolerance—Can You Become Resistant to the Drug?

Hydroxyzine Tolerance—Can You Become Resistant to the Drug?

If you’re among the 35% of adults in the U.S. grappling with sleepless nights, your doctor may prescribe hydroxyzine, an antihistamine that can also be a short-term solution for sleeplessness. Still, your body may develop hydroxyzine tolerance, especially if you use the drug beyond the recommended treatment duration.

Learn more about this potential downside to the otherwise effective medication and find out how to prevent it by following the general guidelines for safe and proper use.

What Is Hydroxyzine?

Hydroxyzine is a prescription-only medication typically recommended for treating the symptoms of allergic reactions, anxiety, and tension. The medication’s active component is hydroxyzine dihydrochloride, classified as a histamine H1 antagonist.

The drug is FDA-approved, and it’s not listed in the DEA’s schedule of controlled substances since it doesn’t carry the risk of physical addiction. Still, the possibility of misuse can’t be disregarded, so following the instructions for safe use is essential.

The table below highlights basic details about hydroxyzine:



Active component

Hydroxyzine dihydrochloride

FDA approval 


Controlled Substance


Prescription or OTC


Drug form

Capsule, liquid, tablet

Available doses

10 mg, 25 mg, 50 mg, 100 mg

Suitable for pregnant women


Suitable for children

Yes (only for treating allergies)

Treatment duration

3–4 months maximum

Addiction risk

Low (psychological addiction can’t be ruled out)

How Hydroxyzine Works

Hydroxyzine works in two ways:

  1. It blocks histamine activity at the histamine H1 receptors, reducing your body’s response to allergens and providing relief from itching, sneezing, hives, and other symptoms of allergic reactions
  2. It acts on the serotonergic receptors (5HT2) in the brain, boosting the production of serotonin—a neurotransmitter that regulates mood and increases melatonin production, consequently promoting sleep

Due to its fast action and efficacy, doctors sometimes prescribe this medication for short-term treatment of insomnia.

How Is Hydroxyzine Dosed for Sleep?

Hydroxyzine comes in liquid, tablet, and capsule forms. Check out the table below for details on the available doses for each form:

Hydroxyzine Form

Available Doses

Oral tablet (typically taken for sleep issues)

  • 10 mg

  • 25 mg

  • 50 mg

  • 100 mg

Oral capsule

  • 10 mg

  • 25 mg

  • 50 mg

  • 100 mg

Oral syrup

  • 10 mg

Intramuscular injection

  • 10 mg

  • 25 mg

The average starting dose for adults with insomnia is 50 mg, taken 60 minutes before bed. Your exact dose will depend on your health history and the underlying cause and severity of your sleep problems.

You should consult your doctor for specific dosing guidelines and follow all instructions to reduce the risk of unwanted effects.

Source: Kampus Production

Can You Develop Tolerance to Hydroxyzine?

When using hydroxyzine, you should follow three crucial guidelines:

  1. Only take the prescribed dose—If you miss a dose, don’t combine it with the next one
  2. Take the drug at the recommended time—This gives it enough time to kick in without interfering with your schedule
  3. Take the medicine for the specified duration—If you experience sleepless nights after treatment discontinuation, inform your doctor instead of restarting hydroxyzine

Patients who adhere to the guidelines above rarely develop hydroxyzine tolerance, while those who fail to follow all three guidelines may develop tolerance to this drug. In that case, they may need higher doses to feel its effects, which can lead to psychological addiction.

What Are the Side Effects of Long-Term Hydroxyzine Use?

Hydroxyzine is meant for short-term use, typically a maximum of four months. There’s limited scientific evidence on the side effects of using this drug for long periods. A recent study associates it with a higher risk of dementia and Alzheimer’s disease, especially when administered to older patients. 

Using this medicine in the long term may lead to the following side effects:

  • Headache
  • Severe fatigue
  • Dry mouth
  • Blurry vision
  • Chest pain
  • Difficulty swallowing
  • Heart palpitations
  • Fainting
  • Slow heartbeat
  • Vomiting
  • Nausea
  • Swelling
  • Seizures

The list above isn’t exhaustive, so you should inform your doctor if you experience any unusual body changes while on this medication. If you feel drowsy the next day, avoid activities that require sharp focus, such as driving and operating heavy machinery, until the side effect subsides.

Alternatives to Hydroxyzine for Sleep


Although hydroxyzine is generally safe and effective, it isn’t suitable for everyone. Check out the table below for more details:

Who Should Use Hydroxyzine?

Who Shouldn’t Use Hydroxyzine?

  • Adults (18+)

  • Patients with tension and anxiety

  • Individuals with hives, itching, runny nose, watery eyes, and other symptoms of allergic reactions

  • Individuals with low blood pressure

  • Patients who are pregnant, planning to get pregnant, or breastfeeding

  • Individuals with a history of long QT syndrome

  • Patients with heart disease

  • People who took MAO inhibitors in the past 14 days

  • Patients with glaucoma

  • Individuals with gastrointestinal or urinary tract obstruction

  • People who are allergic to the drug or some of its components

If your doctor decides that the risks of using hydroxyzine outweigh the benefits based on your health history and sleep problems, they may recommend other sleep medications, such as:

Are Hydroxyzine and Its Alternatives Effective in Treating Sleeplessness?

While hydroxyzine and its alternatives can provide relief from sleepless nights, insomnia often stems from complex factors, including your health and sleeping habits. To get a lasting solution, you should visit a sleep specialist.

With only 1% of physicians trained in sleep medicine and 50–70 million adults in the U.S. grappling with sleep issues, most experts have their hands full. This makes it hard to get an appointment with a sleep doctor.

The good news is that telemedicine platforms can connect you with sleep medicine specialists pretty quickly. Kick, an online performance medicine clinic, lets you consult specialists almost instantly.

Kick—Your Best Night’s Sleep Designed by Experts

Source: Anna Nekrashevich

Designed by a Stanford sleep specialist, Kick’s program connects you with sleep doctors with years of expertise. Our team offers all-encompassing services and guides you throughout the treatment.

Once you join the program, our experts will prescribe two trial medications that you’ll rotate for two weeks to reduce the risk of dependence and tolerance to one drug. Our medications include:

  • Hydroxyzine
  • Doxepin
  • Ramelteon
  • Cyclobenzaprine
  • Trazodone
  • Gabapentin

These gentle yet fast-acting drugs help you get relief from sleepless nights in the shortest time possible. Your doctor will check in frequently and adjust the treatment if necessary, helping you quickly rediscover your best night’s sleep. Our expert will also use cognitive behavioral therapy for insomnia (CBT-i) best practices to help you improve your sleep hygiene. 

Kick’s sleep program is risk-free. If our team decides we don’t have the best solution for your sleep problems, you won’t pay for the initial consultation as per our Doctor Guarantee.

How Kick Works

Kick’s sleep program has helped many patients overcome sleepless nights, which is evidenced by glowing Trustpilot reviews:

“Easy process, great service, and quick delivery. Prescription works great! Happy to order again!”

Peter, M., U.S.

To benefit from Kick’s sleep program, follow these three simple steps:

  1. Navigate to our Sleep Visit page to start your brief consultation
  2. Fill us in on your medical history and sleep issues
  3. Enter your delivery and billing details

The process is discreet and convenient—you can choose between local pharmacy pickup and home delivery.

Our team will review your details within 24 hours and design a personalized treatment for your sleep issues. Join Kick today and experience the efficacy of our groundbreaking sleep program first-hand.

Source: Yan Krukau

Getting Off Hydroxyzine—What To Expect?

While hydroxyzine isn’t addictive when used in the short term, some patients may develop psychological dependence and withdrawal-like symptoms if they don’t use the drug as prescribed. Before stopping this medication, you should consult your healthcare provider. They can provide a safe and effective plan to discontinue the drug, minimizing the risk of unwanted reactions, including:

  • Anxiety
  • Dizziness
  • Headache
  • Irritability
  • Nausea
  • Seizures (in severe cases)

These symptoms can be uncomfortable and often make it difficult to stop taking the medication. If you experience any of these side effects, you should seek immediate medical attention.

Guidelines for Stopping Hydroxyzine Treatment Safely

To reduce the risk of unwanted reactions when discontinuing hydroxyzine, you should follow these steps:

  1. Consult your doctor—You should always talk to your healthcare provider before making changes to your treatment
  2. Taper off gradually—Instead of stopping hydroxyzine abruptly, you should reduce the daily dose gradually
  3. Monitor your symptoms—Watch out for unusual physical changes and inform your doctor if you notice concerning symptoms
  4. Stay hydrated and maintain a healthy diet—Proper hydration and nutrition can help your body cope with the changes
  5. Go for routine consultations—Your doctor will assess your progress and adjust the treatment plan

Hydroxyzine Interactions

Hydroxyzine can interact with food and other substances as outlined in the table below:


Interaction With Hydroxyzine


Antihistamines (e.g., Benadryl, doxylamine)

Can enhance the side effects

You shouldn’t mix hydroxyzine with other antihistamines unless your doctor recommends it

Antidepressants (e.g., Zoloft, trazodone)

Can raise the risk of side effects

Consult your doctor before mixing these medications

Anticonvulsants (e.g., gabapentin)

Can contribute to drowsiness

You should take lower doses if you must combine these medications

Sleep or anxiety medications (e.g., Belsomra, Ativan, Xanax)

Can enhance drowsiness

Consult your doctor for personalized advice

Muscle relaxants (e.g., cyclobenzaprine)

Can contribute to drowsiness and raise the risk of accidental injury

You shouldn’t mix hydroxyzine with cyclobenzaprine without your doctor’s approval

Dietary supplements (e.g., melatonin, St. John’s wort)

Can raise the risk of drowsiness

You shouldn’t combine hydroxyzine with St. John’s wort or melatonin unless instructed by your doctor

Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen)

The potential for interaction is low, but risks can’t be disregarded

You can take hydroxyzine and ibuprofen if your doctor approves it

Hypnotics (e.g., Ambien)

Can add to the risk of drowsiness

Contact your healthcare provider for personalized advice

Depressants (e.g., Valium)

Can enhance drowsiness

Consult a healthcare professional before mixing these medications

Beta-blockers (e.g., propranolol)

Can raise the risk of dizziness

Unless instructed by your doctor, you should avoid mixing hydroxyzine with beta-blockers

Birth control

No known interactions, but risks can’t be ruled out

Talk to your healthcare provider for personalized advice

Grapefruit and grapefruit juice

Can increase hydroxyzine dihydrochloride levels in the blood

You shouldn’t mix hydroxyzine with grapefruit or grapefruit juice


Can reduce hydroxyzine’s efficacy for sleep

You shouldn’t combine hydroxyzine with caffeine

The table above provides general guidelines for combining hydroxyzine with other substances. To prevent unwanted interactions with the drug, consult your doctor before mixing the medication with other substances and follow their instructions.

Featured image source: Polina Kovaleva