What is the interaction between Trazodone (an antidepressant) and Alprazolam (Xanax, a benzodiazepine)?

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Last updated: March 24, 2025 • View editorial policy

From the Guidelines

I strongly advise against combining trazodone and Xanax (alprazolam) without medical supervision due to potentially dangerous interactions. Both medications affect the central nervous system and when taken together can cause excessive sedation, dizziness, confusion, difficulty breathing, and impaired coordination. Trazodone is primarily used for depression and insomnia, while Xanax treats anxiety disorders.

Key Considerations

  • The combination of these medications can lead to serious adverse effects, including respiratory depression, which can be life-threatening 1.
  • Trazodone and Xanax have different mechanisms of action, with trazodone affecting serotonin receptors and Xanax enhancing GABA activity in the brain 1.
  • If you're struggling with both anxiety and sleep issues, consult your healthcare provider who might prescribe one medication or carefully manage both with appropriate dosing and timing.
  • A healthcare provider might recommend taking trazodone (50-100mg) at bedtime for sleep and a low dose of Xanax (0.25-0.5mg) during the day for anxiety, with careful monitoring 1.
  • The choice of medication and dosage should be directed by symptom pattern, treatment goals, past treatment responses, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and side effects 2.
  • It's essential to follow the recommended sequence of medication trials, starting with short-intermediate acting benzodiazepine receptor agonists or ramelteon, and then considering sedating antidepressants like trazodone if necessary 2.

From the Research

Interaction between Trazodone and Alprazolam

There are no direct studies on the interaction between Trazodone and Alprazolam in the provided evidence. However, some studies provide information on the use of Trazodone as an alternative anxiolytic in patients dependent on benzodiazepines, such as Alprazolam.

Trazodone as an Alternative Anxiolytic

  • A study published in 1993 3 found that Trazodone can be used as an alternative anxiolytic in benzodiazepine-dependent patients, with minimal withdrawal phenomena occurring during the benzodiazepine taper period.
  • The study also found that patients remained off benzodiazepines and showed no evidence of abuse of Trazodone during a 1-year follow-up period.
  • The dose of Trazodone was significantly reduced, and ratings of anxiety and depressive symptoms improved during follow-up.

Pharmacology and Clinical Practice

  • A review of the clinically relevant evidence pertaining to the use of Trazodone in major depressive disorder, published in 2019 4, found that Trazodone is an antidepressant with a favorable profile for the treatment of depression.
  • The review also found that Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain, and sexual side effects.
  • Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety, or psychomotor agitation.

Limitations

  • There are no direct studies on the interaction between Trazodone and Alprazolam in the provided evidence.
  • The studies provided do not specifically address the interaction between Trazodone and Alprazolam, but rather the use of Trazodone as an alternative anxiolytic in patients dependent on benzodiazepines.

References

Guideline

clinical guideline for the evaluation and management of chronic insomnia in adults.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2008

Guideline

clinical guideline for the evaluation and management of chronic insomnia in adults.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2008

Research

Trazodone in benzodiazepine dependence.

The Journal of clinical psychiatry, 1993

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.