Benadryl With Zoloft Interaction

In our latest question and answer, our pharmacist discusses the potential interaction between Benadryl and Zoloft.

Question

How long after taking 12.5 mg of Benadryl can I take Zoloft? My doctor started Zoloft and I’m wondering if I should wait til the next day.

Asked by Sammijojo On Aug 02, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Aug 02, 2022
Last updated Mar 28, 2024

Key points

  • Taking Benadryl with Zoloft could potentially cause additive side effects, most notably, drowsiness.
  • The increased risk of drowsiness is something to be aware of, especially in older adults, due to the risk of falling and the subsequent injuries that can occur.

Answer

Hello and thanks for reaching out to us. I'm more than happy to talk about the safety of combining Benadryl (diphenhydramine) and Zoloft (sertraline).

Benadryl and Zoloft don't interact with one another in terms of either affecting how the other works. However, combining both could lead to some additive side effects, specifically drowsiness. This can be bothersome in its own right and is particularly something to be concerned about in older adults due to the increased risk of falling.

Zoloft Side Effects

Now, Zoloft can affect everyone a little differently in regard to side effects, and side effects from the drug tend to be a little more pronounced when it is first started. The most commonly reported side effects of Zoloft are:

  • Nausea
  • Somnolence (i.e. sleepiness)
  • Sexual dysfunction
  • Insomnia
  • Headaches
  • Restlessness
  • Dizziness

You'll notice some of these side effects seem to conflict with one another (e.g. Zoloft can cause both sleepiness and insomnia). Again, the side effects experienced from the drug do vary from person to person, and can vary even based on how long you have been taking it. Insomnia tends to be a problem when the drug is first started, while sleepiness and dizziness may be more pronounced later.

Benadryl Side Effects

Benadryl is a first-generation antihistamine that can be used for allergy symptoms, but it is also very commonly used as a sleep aid due to its sedative effects.

The most common side effects of Benadryl are:

  • Nausea
  • Dry mouth
  • Sleepiness
  • Constipation

Taking Zoloft With Benadryl

As mentioned, there is no drug interaction between Zoloft and Benadryl in the fact that they don't affect how the other drug works. Nevertheless, combining them could certainly cause some additive side effects such as an increased feeling of drowsiness.

 I do want to point out here as well that combining Zoloft and Benadryl may be particularly risky in older adults due to this increased sedation.

SSRIs (selective serotonin reuptake inhibitors), like Zoloft, have been linked to an increased risk of falling. Some studies, including one published in the New England Journal of Medicine, show that elderly individuals taking an SSRI have around a two-fold increased risk of falling versus those not taking SSRIs. This is of course concerning due to the injuries that can happen when a fall occurs.

How Long To Wait After Taking Benadryl

You asked in your question specifically how long to wait after taking Benadryl to take Zoloft. Benadryl is relatively short-acting, with a duration of action of around 4 to 6 hours per dose, although this can be longer in older adults.

As a rule of thumb, you'll want to wait at least 6 hours after taking Benadryl to take Zoloft if you want to try to avoid the risk of additive side effects from both drugs.

Final Words

Thanks again for reaching out to us and we hope to hear from you again soon!

References

  • Diphenhydramine Monograph, PubChem
  • Sertraline Monograph, PubChem
  • Antidepressants and the risk of falls among nursing home residents, PubMed
  • Zoloft Prescribing Information, AccessFDA
  • PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder, Psychiatry Online

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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