Benadryl Amitriptyline Drug Interaction

The pharmacist discusses the potential drug interaction between Benadryl and amitriptyline.

Question

I take amitriptyline to help sleep once in awhile but it often doesn't do the trick. Is it okay to take with Benadryl?

Asked by Johnathan On Jul 03, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jul 03, 2018

There is a moderate drug interaction between Benadryl and Amitriptyline. The use of these medications together may not be ideal as the side effects of each can be additive and result in potentially harmful outcomes.


Amitriptyline is a tricyclic antidepressant, and is used for the treatment of depression (becoming less and less used as new and safer drugs are becoming available). It works by increasing various neurotransmitters in the brain (e.g. serotonin) that may be altered in individuals suffering from depression. Some of the common side effects of this medication are:

  • Constipation
  • Less urinary frequency
  • Abdominal cramping
  • Drowsiness


Benadryl is an antihistamine that is also known to have drying side effects due to its anticholinergic properties. Some of the common side effects associated with the use of Benadryl are:

  • Dry mouth
  • Constipation
  • Difficulty urinating
  • Decrease in mucus production
  • Sedation
  • Drowsiness


Additive Side Effects Of Benadryl And Amitriptyline

Despite not having the same use, Benadryl and amitriptyline have similar side effects which can be additive when used together. These additive toxicities must be considered before starting or recommending the use of Benadryl as serious complications including severe constipation, drowsiness and confusion can occur. In addition, be sure to ask your doctor regarding the use of the medications if you have a history of:

  • BPH (enlarged prostate)
  • Narrow angle glaucoma

About the Pharmacist

Dr. Hayden Gharibyar

Dr. Hayden Gharibyar is a Doctor of Pharmacy graduate from the University of Colorado. His areas of expertise include pharmacovigilance and drug safety.

About Benadryl (Diphenhydramine)

Benadryl (diphenhydramine) is a first generation, sedating antihistamine (H1-blocker) of the ethanolamine class. It is available in oral, topical, and parenteral product forms. Benadryl is well known to cause significant sedation in most individuals and is commonly used in night-time sleep aids. Benadryl also has potent "drying" effects in most patients, which is why is causes dry mouth, dry eyes and constipation. The onset of action of Benadryl is around 15-30 minutes after taking by mouth, with peak effects occurring 1 to 3 hours later. The duration of action is around 4 to 6 hours, with this being prolonged in the elderly and in those with liver disease.

About Elavil (Amitriptyline)

Elavil (amitriptyline) is a tricyclic antidepressant (TCA), which is metabolized in the body to the active metabolite nortriptyline. The exact mechanism of action of amitriptyline is not fully understood, but is thought to increase levels of of norepinephrine and serotonin. Amitriptyline is used for a wide range of indications including depression, anxiety and insomnia. Compared to other antidepressants, amitriptyline is generally more sedating and has greater anticholinergic effects, which increases the risk of side effects such as constipation, dry mouth and confusion, especially in the elderly.

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