Can I take Benadryl (Diphenhydramine) with Nortriptyline?

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From the Guidelines

I strongly advise against taking Benadryl (diphenhydramine) with nortriptyline due to the potential for increased anticholinergic side effects and interactions. While the provided evidence does not directly address the interaction between Benadryl and nortriptyline, it does suggest that diphenhydramine is not recommended for sleep onset and sleep maintenance insomnia in adults 1. This is relevant because both medications have anticholinergic properties, which can compound when taken together. The combination of these medications may increase the risk of side effects like drowsiness, dry mouth, blurred vision, and confusion.

Key Considerations

  • The potential for increased anticholinergic side effects, such as dry mouth, blurred vision, and confusion, when taking Benadryl with nortriptyline
  • The risk of compounded sedation, as both medications can cause drowsiness
  • The importance of consulting with a healthcare provider to determine the best course of treatment for allergies or insomnia while taking nortriptyline
  • Alternative allergy medications, such as non-sedating antihistamines like loratadine or cetirizine, may be recommended to minimize potential interactions

Recommendations for Patients

  • Consult with a healthcare provider before taking Benadryl with nortriptyline
  • Discuss alternative allergy medications or treatments with a healthcare provider
  • Be aware of the potential side effects and interactions when taking these medications together
  • Follow the recommended dosage and timing of medications to minimize interactions, as suggested by a healthcare provider 1.

From the Research

Interaction between Benadryl (Diphenhydramine) and Nortriptyline

  • There are no direct studies on the interaction between Benadryl (Diphenhydramine) and Nortriptyline in the provided evidence.
  • However, studies have shown that diphenhydramine can impair psychomotor performance and cognitive function 2, 3.
  • Nortriptyline is a tricyclic antidepressant that is occasionally used for treating neuropathic pain, and its combination with other medications can have varying effects 4, 5.
  • A study on the central nervous system effects of H1-receptor antagonists in the elderly found that newer H1-receptor antagonists such as cetirizine and loratadine caused less central nervous system dysfunction than older H1-receptor antagonists like diphenhydramine 6.
  • The sedating effects of diphenhydramine can be a concern when combined with other medications, and it is essential to consider the potential risks and benefits of such combinations 2, 3, 6.

Potential Risks and Considerations

  • The combination of diphenhydramine and nortriptyline may increase the risk of sedation, impaired cognitive function, and other adverse effects.
  • Patients taking this combination should be monitored closely for signs of adverse effects, such as somnolence, dry mouth, and constipation 4.
  • The evidence suggests that newer antihistamines may be a safer alternative to diphenhydramine, but more research is needed to fully understand the potential interactions between these medications 2, 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nortriptyline for neuropathic pain in adults.

The Cochrane database of systematic reviews, 2015

Research

Central nervous system effects of H1-receptor antagonists in the elderly.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 1999

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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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