Taking Benadryl With Wellbutrin, Effexor And Gabapentin

In our latest question and answer, the pharmacist discusses whether or not Benadryl interacts with Wellbutrin, Effexor or gabapentin.


I take 100mg Wellbutrin and 37.5mg Effexor in the morning and 600mg gabapentin in the evening, can I take Benadryl with these medications?

Asked by Shawna On Apr 08, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Apr 08, 2018

Benadryl does have reported interactions with some of your medications. However, they are not contraindications, but they should be considered before deciding to take Benadryl with your current medications.

Benadryl, generic name diphenhydramine, is an antihistamine that works by competing with histamine for the binding sites. Benadryl can be used for several indications including:

  • Allergies or allergic reaction
  • Cold/flu symptoms
  • Sleep aid
  • Motion sickness

Side effects of diphenhydramine include symptoms of CNS depression including drowsiness, confusion, dizziness, and dry mouth.

Below, we discuss whether or not Benadryl interacts with the medications in question.

Taking Benadryl With Gabapentin

Gabapentin is used for a wide variety of indications such as neuropathy and epilepsy.

Gabapentin is a CNS depressant. Concurrent use of 2 or more drugs that can cause CNS depression (such as with Benadryl) may increase the chance of side effects, such as:

  • Increased drowsiness
  • Sedation
  • Confusion
  • Respiratory depression

These agents should be used in combination with caution in particularly for patients >65 years old and with certain health conditions. If you choose to take these drugs together, you should start with low doses of Benadryl to see how it affects you.

Taking Benadryl With Effexor

Effexor is an antidepressant, most commonly used for the treatment of major depressive disorder.

Benadryl and Effexor both have the potential to cause QTc prolongation. QTc prolongation can be a marker for potential arrhythmias or irregular heart rate. For most healthy patients this is not a major concern and does not require dose adjustment or holding either medication. However, there are certain people who are at a higher risk for developing this arrhythmia or a more serious complication.

Risk factors for QTc prolongation include:

  • Age >65 years old
  • Bradycardia (slow heart rate)
  • History of heart disease or arrhythmias
  • Electrolyte imbalances such as low potassium or magnesium.

If you have one of these risk factors, talk to your doctor before taking Benadryl and Effexor together.  

Taking Benadryl With Wellbutrin

There is no reported interactions between Benadryl and Wellbutrin. They are considered to be safe to take with each other.


  • There are some reported drug interactions between Benadryl and your current medications (Effexor & gabapentin).
  • In most people, these interactions are not a major concern and taking Benadryl to treat allergies or as a sleep aid is safe.
  • If you are in one of the risk groups listed in the descriptions above, it would be recommended to talk to your doctor before mixing Benadryl with Effexor or gabapentin.

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.

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