Can Hydroxyzine (Atarax) and Trazodone Be Given Together?
Yes, hydroxyzine and trazodone can be safely co-administered for insomnia and anxiety, but this combination requires cardiac monitoring due to additive QTc prolongation risk and careful attention to sedation.
Cardiac Safety Considerations
Both hydroxyzine and trazodone prolong the QTc interval, and their combined use creates additive arrhythmic risk, including torsades de pointes and sudden cardiac death. 1
Obtain a baseline electrocardiogram before initiating combination therapy and monitor the QTc interval continuously; discontinue both medications immediately if QTc exceeds 500 ms or increases by more than 60 ms from baseline. 1
Screen for additional QTc-prolonging risk factors including female sex, age >65 years, electrolyte abnormalities (hypokalemia, hypomagnesemia), bradycardia, and concurrent use of other QT-prolonging drugs (macrolides, fluoroquinolones, antiarrhythmics). 1
Central Nervous System Depression
The combination produces additive CNS depression, significantly increasing the risk of respiratory depression, cognitive impairment, falls, fractures, and complex sleep behaviors (sleep-driving, sleep-walking). 1
This additive sedative effect is especially hazardous in older adults, where it markedly amplifies psychomotor impairment and fall risk. 1
During the first 24–48 hours after initiation, closely observe for excessive sedation, confusion, falls, and respiratory depression. 1
Dosing Strategy When Combination Is Necessary
Start with lower doses of each medication:
Elderly patients or those with hepatic impairment require even lower starting doses due to increased sensitivity to sedative effects. 1
Avoid combining with other CNS depressants including alcohol, benzodiazepines, or opioids due to compounded respiratory depression risk. 1
Monitoring Requirements
Regular follow-up every 2–4 weeks during initial treatment to assess efficacy, monitor for side effects, and check blood pressure for orthostatic hypotension. 1
Monitor blood pressure regularly, particularly when initiating therapy or adjusting doses, as both medications can cause orthostatic hypotension. 1
Patients should be cautioned about activities requiring alertness (driving, operating machinery) until the effects of the combination are known. 1
Safer Alternative Approaches
For Anxiety Management
- If hydroxyzine is being used primarily for anxiety, replace it with an SSRI (sertraline) or buspirone, both of which lack QTc-prolonging properties and are safer when combined with trazodone. 1
For Insomnia Management
The American Academy of Sleep Medicine explicitly recommends against trazodone for insomnia due to minimal benefit (only ~10 minutes reduction in sleep latency, ~8 minutes reduction in wake after sleep onset) with no improvement in subjective sleep quality, and harms outweigh benefits. 2, 3
The American Academy of Sleep Medicine recommends against over-the-counter antihistamines (including hydroxyzine) for insomnia due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation), and rapid tolerance development within 3–4 days. 2
First-line insomnia treatment should be Cognitive Behavioral Therapy for Insomnia (CBT-I), which provides superior long-term efficacy compared to medications. 2, 3
If pharmacotherapy is needed after CBT-I initiation, evidence-based options include:
Common Pitfalls to Avoid
Prescribing this combination without baseline ECG and ongoing QTc monitoring exposes patients to preventable arrhythmic death. 1
Using this combination in elderly patients without dose reduction dramatically increases fall and fracture risk. 1
Failing to counsel patients about avoiding alcohol and other CNS depressants can lead to fatal respiratory depression. 1
Continuing this combination long-term without reassessing the need for both agents and exploring safer alternatives. 1