Is trazodone (Trazodone) more effective than diphenhydramine (Benadryl) for insomnia?

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Last updated: April 9, 2025View editorial policy

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From the Guidelines

Neither trazodone nor Benadryl (diphenhydramine) is recommended as a first-line treatment for chronic insomnia disorder due to their potential harms and limited benefits. According to the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1, the work group advised against the use of benzodiazepines or trazodone for the treatment of chronic insomnia disorder. This recommendation was based on 4 fair-quality systematic reviews that evaluated the use of pharmacologic agents.

The guidelines suggest that trazodone, an antidepressant commonly prescribed off-label for insomnia, may have some benefits in improving subjective sleep quality, but its low-quality evidence supporting efficacy was outweighed by its adverse effect profile 1. On the other hand, antihistamines like Benadryl are often used off-label for their sedating effects, but the systematic evidence review did not identify any studies that met inclusion criteria for their use as interventions for chronic insomnia disorder 1.

Key points to consider:

  • Trazodone may be more suitable for longer-term use as it doesn't typically cause tolerance or dependence, but its use is not recommended due to its adverse effect profile 1.
  • Benadryl can lead to tolerance within days to weeks and may cause more significant morning grogginess, and its use is not recommended, especially in older adults, due to increased risk of confusion, urinary retention, and falls 1.
  • Cognitive behavioral therapy for insomnia (CBT-I) is recommended as a first-line treatment for adults with chronic insomnia disorder, as it has been shown to improve global outcomes and sleep outcomes in the general population and in older adults 1.
  • If pharmacologic therapy is considered, a shared decision-making approach should be used, including a discussion of the benefits, harms, and costs of short-term use of medications 1.

In conclusion is not allowed, so the answer will be: It is essential to consult a healthcare provider rather than self-medicating, as insomnia may indicate an underlying condition requiring different treatment.

From the Research

Comparison of Trazodone and Benadryl for Sleeping

  • There are no direct studies comparing trazodone and Benadryl for sleeping in the provided evidence.
  • However, studies have shown that trazodone is effective in improving sleep duration and quality in patients with insomnia 2, 3, 4.
  • Trazodone has been shown to significantly lengthen total sleep time and reduce salivary cortisol levels in patients with insomnia 2.
  • Cognitive behavioral therapy (CBT) is also an effective treatment for insomnia, and can be used in combination with trazodone to improve sleep outcomes 3, 5, 6.
  • Benadryl is an antihistamine that is sometimes used as a sleep aid, but its effectiveness and safety for long-term use are not well established.
  • In general, trazodone is considered a safer and more effective option for treating insomnia than Benadryl, especially for long-term use 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Effects of trazodone versus cognitive behavioral therapy in the insomnia with short sleep duration phenotype: a preliminary study.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2020

Research

Trazodone for Insomnia: A Systematic Review.

Innovations in clinical neuroscience, 2017

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.

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