Anxiolytic & Hypnotic Adverse Events · Section 5 · Chapter 13 · Hydroxyzine
Hydroxyzine for Anxiety: QT Prolongation, Anticholinergic Burden and Sedation
Hydroxyzine is labeled in the US for anxiety and is sometimes chosen as a non-controlled alternative to a benzodiazepine. It is a first-generation antihistamine with real risks: QT prolongation and torsade de pointes, strong anticholinergic effects in older adults, added sedation with other CNS depressants, and a rare serious skin reaction. This chapter covers how to recognize and manage each one.
The 30-second version
- QT prolongation. QT prolongation and torsade de pointes have been reported with hydroxyzine, mostly in patients with other risk factors such as heart disease, electrolyte imbalance or other QT-prolonging drugs. It is contraindicated with a prolonged QT interval. Check for risk factors and QT-prolonging drugs, including several psychotropics, before prescribing.
- Older adults. The 2023 Beers Criteria advise avoiding hydroxyzine in older adults: it is strongly anticholinergic, its clearance falls with age, and cumulative anticholinergic exposure is associated with falls, delirium and dementia. If it is used, the US label advises starting at a low dose and observing closely.
- Sedation. Hydroxyzine potentiates other CNS depressants, including opioids and barbiturates. The US label advises against using other CNS depressants at the same time, says their doses should be reduced when they are given together, and cautions against driving or operating dangerous machinery. Sedating drugs may cause confusion and oversedation in older adults.
- Skin and hypersensitivity. Hydroxyzine can rarely cause acute generalized exanthematous pustulosis, a serious skin reaction: stop it at the first sign of a rash and do not restart it if AGEP is suspected. It is contraindicated in known hypersensitivity to hydroxyzine, cetirizine, levocetirizine or any component of the product.
- Dose and overdose. The European Medicines Agency limits adults to 100 mg a day and advises that older adults not use it, or take no more than 50 mg a day; the US label allows up to 400 mg a day for anxiety. Overdose mainly causes heavy sedation; convulsions can occur, and overdose may cause QT prolongation and torsade de pointes, so ECG monitoring is recommended.
At the visit: a patient on hydroxyzine for anxiety
About 2 min to read · the detailed chapter follows below
Do now
- List every QT-prolonging drug, including antipsychotics, citalopram, fluoxetine, methadone and ondansetron.
- Ask about heart disease, fainting, palpitations, a family history of long QT or sudden death, and anything that could lower potassium or magnesium.
- In a patient 65 or older, count every anticholinergic drug.
- List every CNS depressant, including opioids and alcohol.
- Ask about any rash since starting it.
Do not
- Prescribe it to a patient with a prolonged QT interval.
- Add it to another QT-prolonging drug without weighing the risk.
- Treat it as a harmless sleep or anxiety aid in an older adult.
- Restart it after a suspected AGEP reaction.
- Assume the US maximum dose is safe in a patient with risk factors.
Five questions to ask
- Have you ever fainted, had palpitations, or been told your heart rhythm is abnormal? A prolonged QT interval is a contraindication.
- Does anyone in your family have a heart rhythm problem or died suddenly when young? A family history of long QT or sudden cardiac death is a risk factor.
- What other medicines do you take, including for nausea, infections or pain? Many common drugs also prolong the QT interval.
- Any confusion, falls, constipation or trouble passing urine? These can be anticholinergic effects, especially in older adults.
- Any new rash? A rash means stopping it.
Emergency if any of
- Fainting, seizure or palpitations, especially with another QT-prolonging drug
- Suspected overdose, even if the patient seems well
- A spreading rash, especially with fever or feeling unwell
- Marked confusion or sedation, especially in an older adult
Review the prescription now if any of
- Another QT-prolonging drug, heart disease, low potassium or magnesium, or significant bradycardia
- Age 65 or older, or other anticholinergic drugs
- An opioid, barbiturate or other CNS depressant
- A daily dose above 100 mg, the European adult limit (the US label allows more); review the dose against the patient's QT risk
- Any rash
No problems: review the indication
Use the lowest effective dose for the shortest possible time, reassess its usefulness periodically, and recheck risk factors when other drugs are added.
Prescriber-side triage for hydroxyzine. Our synthesis of the US label, the 2015 European Medicines Agency recommendations and the 2023 AGS Beers Criteria, not a validated instrument [1][2][3].
Why the risks are missed
- It is not a controlled substance and is seen as mild
- QT-prolonging drugs are often added by other prescribers
- Anticholinergic effects in older adults look like aging or dementia
Record in the chart
- Indication and daily dose
- QT risk factors and QT-prolonging drugs
- ECG and electrolytes, if checked
- Anticholinergic drug count
- CNS depressants
Look up the situation
Tap the situation for what it means and what to do.
Act now
Higher risk
Routine check
Fainting, palpitations or a prolonged QT interval
Act nowHydroxyzine is contraindicated in patients with a prolonged QT interval [1].
What to do
- Emergency care for fainting or a seizure
- ECG, potassium and magnesium
- Stop hydroxyzine and review every other QT-prolonging drug
Keep in mind
- Most reported cases had other risk factors [1][2]
- The European Medicines Agency contraindicates use with other QT-prolonging drugs [2]
An older adult
AvoidBeers 2023: avoid first-generation antihistamines, including hydroxyzine (moderate evidence, strong recommendation) [3].
What to do
- Choose a non-anticholinergic option
- If it is used, start low and observe closely [1]
- Count total anticholinergic drugs [3]
Keep in mind
- Beers advises avoiding anticholinergics with delirium or dementia, and with a history of falls or fractures unless safer alternatives are not available [3]
- The European Medicines Agency advises older adults not to use it [2]
Checking the dose
ReviewThe European limit for adults is 100 mg a day; the US anxiety dose is 50 to 100 mg four times a day [1][2].
What to do
- Use the lowest effective dose for the shortest time [2]
- Reduce the dose of other CNS depressants [1]
- Recheck QT risk factors when new drugs are added
Keep in mind
- Older adults: EU maximum 50 mg a day, if used at all [2]
- The two limits come from different regulators; see the detail below
All three situations on one page (figure)
Figure 1. Hydroxyzine risks when it is used for anxiety, and what to do. Our summary of the US label, the 2015 European Medicines Agency recommendations and the 2023 AGS Beers Criteria [1][2][3].
QT prolongation and torsade de pointes
QT prolongation and torsade de pointes have been reported with hydroxyzine, mostly in patients with other risk factors such as heart disease, electrolyte imbalance or other QT-prolonging drugs. It is contraindicated with a prolonged QT interval. Check for risk factors and QT-prolonging drugs, including several psychotropics, before prescribing.
| Point | Finding | Source |
|---|---|---|
| Reports | QT prolongation and torsade de pointes have been reported after marketing; most reports occurred in patients with other risk factors: pre-existing heart disease, electrolyte imbalance or other arrhythmogenic drugs | US label, precautions [1] |
| Contraindication | Prolonged QT interval | US label [1] |
| Use with caution | Congenital long QT syndrome, family history of long QT, other conditions that predispose to QT prolongation and ventricular arrhythmia, recent myocardial infarction, uncompensated heart failure and bradyarrhythmias | US label, precautions [1] |
| QT-prolonging drugs named in the label | Class 1A (such as quinidine and procainamide) and class III (such as amiodarone and sotalol) antiarrhythmics; antipsychotics such as ziprasidone, iloperidone, clozapine, quetiapine and chlorpromazine; antidepressants such as citalopram and fluoxetine; antibiotics such as azithromycin, erythromycin, clarithromycin, gatifloxacin and moxifloxacin; and methadone, ondansetron, droperidol and pentamidine | US label, precautions [1] |
| European restrictions | Contraindicated in known acquired or congenital QT prolongation, or with a known risk factor for it: cardiovascular disease, significant hypokalemia or hypomagnesemia, a family history of sudden cardiac death, significant bradycardia, or other drugs known to prolong the QT interval or induce torsade de pointes. Use with caution with bradycardia or hypokalemia-inducing drugs. Not recommended in older adults | European Medicines Agency 2015 [2] |
The detail: US caution versus European contraindication
The two regulators read the same risk differently. The US label asks for caution when hydroxyzine is combined with other QT-prolonging drugs [1]. The European Medicines Agency, after a 2014–2015 review that confirmed the known risk, contraindicated it both with other QT-prolonging drugs and in patients with any known QT risk factor, and found that most cases involved other risk factors, electrolyte abnormalities or other treatments that may have contributed [2]. Neither source sets a routine ECG schedule. Our approach: before prescribing it to a patient with a risk factor or another QT-prolonging drug, check an ECG and electrolytes, or choose another option.
Older adults and anticholinergic burden
The 2023 Beers Criteria advise avoiding hydroxyzine in older adults: it is strongly anticholinergic, its clearance falls with age, and cumulative anticholinergic exposure is associated with falls, delirium and dementia. If it is used, the US label advises starting at a low dose and observing closely.
| Point | Finding | Source |
|---|---|---|
| First-generation antihistamines | Avoid (moderate evidence, strong recommendation): highly anticholinergic, clearance reduced with advanced age, tolerance develops when used as a hypnotic; cumulative anticholinergic exposure is associated with falls, delirium and dementia, even in younger adults | Beers 2023, Table 2 [3] |
| Delirium, dementia, falls | Avoid anticholinergics in older adults with or at high risk of delirium, with dementia or cognitive impairment, and, unless safer alternatives are not available, with a history of falls or fractures | Beers 2023, Table 3 [3] |
| Combining anticholinergics | Avoid using more than one drug with anticholinergic properties; minimize the number (moderate evidence, strong recommendation) | Beers 2023, Tables 5 and 7 [3] |
| Label advice | Start at the low end of the dosing range; older adults are more likely to have reduced renal function, so take care in dose selection; sedating drugs may cause confusion and oversedation in the elderly; start low and observe closely | US label, geriatric use [1] |
| European advice | Older adults should not use hydroxyzine; if they do, the maximum is 50 mg a day | European Medicines Agency 2015 [2] |
The detail: what the label lists, and what it does not
The US label lists dry mouth as its only anticholinergic adverse reaction [1]. The Beers Criteria nonetheless list hydroxyzine among the drugs with strong anticholinergic properties [3]. In an older adult, confusion, constipation, urinary retention or a fall after starting hydroxyzine is a reason to review it.
Sedation and other CNS depressants
Hydroxyzine potentiates other CNS depressants, including opioids and barbiturates. The US label advises against using other CNS depressants at the same time, says their doses should be reduced when they are given together, and cautions against driving or operating dangerous machinery. Sedating drugs may cause confusion and oversedation in older adults.
| Point | Label wording | Source |
|---|---|---|
| Potentiation | The potentiating action of hydroxyzine must be considered when it is used with CNS depressants such as narcotics, non-narcotic analgesics and barbiturates; their dosage should be reduced | US label [1] |
| Driving and alcohol | Warn patients that drowsiness may occur; caution against driving or operating dangerous machinery; advise against using other CNS depressants at the same time; the effects of alcohol may be increased | US label, precautions [1] |
| Older adults | Sedating drugs may cause confusion and oversedation in the elderly | US label, geriatric use [1] |
| Breathing | Clinically significant respiratory depression has not been reported at recommended doses; the caution about opioids and other CNS depressants still applies | US label, adverse reactions [1] |
Skin reactions and hypersensitivity
Hydroxyzine can rarely cause acute generalized exanthematous pustulosis, a serious skin reaction: stop it at the first sign of a rash and do not restart it if AGEP is suspected. It is contraindicated in known hypersensitivity to hydroxyzine, cetirizine, levocetirizine or any component of the product.
| Point | Label wording | Source |
|---|---|---|
| AGEP | May rarely cause acute generalized exanthematous pustulosis, a serious skin reaction; discontinue at the first appearance of a skin rash; do not resume if signs suggest AGEP | US label, precautions [1] |
| Cross-reactivity | Contraindicated in known hypersensitivity to hydroxyzine, cetirizine, levocetirizine or any component of the product; avoid cetirizine or levocetirizine after AGEP or other hypersensitivity reactions with hydroxyzine | US label [1] |
| Other skin reactions | Fixed drug eruptions (postmarketing), pruritus, rash and urticaria | US label, adverse reactions [1] |
Dose limits and overdose
The European Medicines Agency limits adults to 100 mg a day and advises that older adults not use it, or take no more than 50 mg a day; the US label allows up to 400 mg a day for anxiety. Overdose mainly causes heavy sedation; convulsions can occur, and overdose may cause QT prolongation and torsade de pointes, so ECG monitoring is recommended.
| Point | Finding | Source |
|---|---|---|
| US anxiety dose | Adults: 50 to 100 mg four times a day | US label, dosage [1] |
| European limits | Adults: no more than 100 mg a day. Older adults: should not use it; if they do, no more than 50 mg a day. Children up to 40 kg: no more than 2 mg/kg a day. Use the lowest effective dose for the shortest possible duration | European Medicines Agency 2015 [2] |
| Long-term use | Effectiveness as an anxiolytic for more than 4 months has not been assessed in systematic clinical studies; reassess its usefulness periodically | US label, indications [1] |
| Seizures and hallucinations | Involuntary motor activity, including rare tremor and convulsions, has been reported, usually at doses considerably higher than recommended; hallucination is listed among postmarketing reports | US label, adverse reactions [1] |
| Pregnancy | Contraindicated in early pregnancy | US label [1]; see the Perinatal Psychopharmacology series |
| Overdose | The most common manifestation is hypersedation; convulsions, stupor, nausea and vomiting have also been reported. Overdose may cause QT prolongation and torsade de pointes, and ECG monitoring is recommended. Hypotension, though unlikely, may be treated with intravenous fluids and levarterenol or metaraminol; do not use epinephrine, because hydroxyzine counteracts its pressor action. There is no specific antidote, and hemodialysis is doubtful unless other agents such as barbiturates were also taken | US label, overdosage [1] |
The detail: which limit to follow
The US label's anxiety dose allows up to 400 mg a day [1]. The European Medicines Agency's 2015 limit of 100 mg a day for adults was set to reduce the risk of QT prolongation [2]. The European limit does not bind US prescribing, but it reflects the same risk. Our view: for a US patient in whom hydroxyzine remains appropriate after risk assessment, the 100 mg a day limit is the more conservative ceiling. A lower dose does not make it appropriate with a prolonged QT interval, or with the QT risk factors and QT-prolonging drugs that the European Medicines Agency contraindicates. In an overdose, follow current poison center advice; the label's decontamination instructions, which include inducing vomiting, should not be applied without that advice.
Clinical pearls
- Not controlled does not mean low risk.
- A prolonged QT interval is a contraindication.
- Check the QT list before adding it to an antipsychotic, citalopram or methadone.
- Beers: avoid it in older adults.It is strongly anticholinergic.
- Reduce the dose of other CNS depressants when combining.
- A rash means stop.Do not restart it after suspected AGEP.
- The European adult limit is 100 mg a day.
Patient script & EMR note
Counseling script: when prescribing hydroxyzine for anxiety
"This is an older antihistamine that can take the edge off anxiety. It can make you drowsy, so don't drive or operate dangerous machinery while you're taking it. Avoid alcohol and other sedating medicines, and check with me before combining it with pain medicines or other sedatives.
Rarely, it can affect the heart's rhythm. Tell me or your pharmacist before starting any new medicine, including antibiotics or anti-nausea drugs. If you faint, feel your heart racing or pounding, or have a seizure, call 911.
If you get a rash, stop it and call me; if the rash spreads quickly, you get a fever, or you feel unwell with it, go to an emergency department now. Older people can get confused, constipated or unsteady on it, so let me know if that happens."
EMR note: copy, paste and edit
HYDROXYZINE – REVIEW
Indication: [ ] Daily dose: [ ] mg
Age: [ ] (65+: Beers avoid)
QT risk factors (heart disease, long QT,
family history, bradycardia): [ ]
QT-prolonging drugs: [ ]
K / Mg: [ ] ECG / QTc: [ ]
Anticholinergic drugs (count): [ ]
CNS depressants / opioids / alcohol: [ ]
Rash / prior AGEP / hypersensitivity to
hydroxyzine, cetirizine, levocetirizine
or a product component: [ ]
Confusion, falls, constipation,
urinary retention: [ ]
Plan:
[ ] Continue; lowest dose, shortest time
[ ] Reduce to: [ ] (EU max if used: adults
100 mg/day; older adults 50 mg/day)
[ ] Stop; alternative: [ ]
[ ] ECG / electrolytes: [ ]
[ ] Next review: 2026
Clinician: [ ] Date/time: [ ]
Case: Friday, 10:00 am
A 71-year-old woman with generalized anxiety takes citalopram and was started on hydroxyzine 25 mg three times a day a month ago. She also takes furosemide, and her potassium last week was 3.2 mmol/L. Her daughter says she has been confused in the evenings and nearly fell getting up at night. She has had no fainting or palpitations.
By the end of this chapter you should be able to name the problems and what to change.
Case resolution
The Beers Criteria advise avoiding hydroxyzine in older adults, and her new confusion and near-fall add clinical reasons to stop and reassess it [3]; the European Medicines Agency advises that older adults not use it, and at most 50 mg a day if they do, while she takes 75 mg [2]. Citalopram is named in the US label as a QT-prolonging drug [1]. Under the European restrictions, the combination with citalopram is a contraindication, use is not recommended at her age, and her low potassium is a QT risk factor that needs correcting; the agency contraindicates use with significant hypokalemia but does not define a threshold [2]. Her evening confusion and near-fall fit the label's warning that sedating drugs may cause confusion and oversedation in the elderly [1].
Hydroxyzine is stopped. Neither source gives tapering instructions for hydroxyzine, so how to stop it is clinical judgment. An ECG is checked, her potassium and magnesium are measured and corrected if low with her primary care clinician, and her other medicines are reviewed for anticholinergic and QT effects. Her anxiety treatment is reviewed without adding another anticholinergic or sedating drug, and her daughter is told to call 911 if she faints.
Why it matters
Hydroxyzine is often chosen because it is not a benzodiazepine and not controlled. It can end up alongside antipsychotics, antidepressants and opioids, and in older adults. Its QT and anticholinergic risks are in the label and the Beers Criteria, but they are easy to miss when the drug is seen as mild. A check of the QT list, the patient's age and the other sedating drugs takes a minute.
References (3)
- Hydroxyzine hydrochloride tablets, USP [US prescribing information]. Aurobindo Pharma Limited. Indications and usage, contraindications, warnings, precautions (including geriatric use), adverse reactions, overdosage and dosage. DailyMed listing revised March 2026 (label text dated October 2021). Source type: US product label.
- European Medicines Agency. New restrictions to minimise the risks of effects on heart rhythm with hydroxyzine-containing medicines. 27 March 2015. Source type: regulatory communication (EU).
- By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052–2081. doi:10.1111/jgs.18372. Tables 2, 3, 5 and 7. Author manuscript: PMC12478568. Source type: consensus criteria (peer-reviewed).
Last reviewed October 2026. Part of the Psychiatry Education Forum Academy, Managing Anxiolytic & Hypnotic Adverse Events · Section 5 · Chapter 13.
Managing Anxiolytic & Hypnotic Adverse Events
The rest of the course applies the same rapid-decision format to the serious adverse effects of other anxiolytics and hypnotics.
This chapter is educational material for licensed prescribers and prescribers in training. It is not a substitute for clinical judgment, local protocols, poison center advice or the current prescribing information. Do not prescribe hydroxyzine with a prolonged QT interval; fainting, a seizure or a suspected overdose needs emergency care. Psychiatry Education Forum Academy is not a CME provider and this chapter does not carry CME credit.
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