Can I Take Benadryl with Zoloft?

If you live with allergies, over-the-counter diphenhydramine (Benadryl) might be a staple in your medicine cabinet. However, anyone prescribed sertraline (Zoloft) should speak with a doctor before also taking Benadryl since there’s an increased  when these drugs are combined. Continue reading to learn about the possible interactions between Benadryl and Zoloft.

Benadryl and Zoloft Interactions: Sedation and CNS Depression

As with most medications, Benadryl and Zoloft are beneficial for treating certain conditions but are also associated with risks.

Benadryl is from the class of drugs called antihistamines. As the name indicates, it is typically used to block allergy-causing histamines. But this medication isn’t just reserved for treating allergies. It can also help manage motion sickness.

A primary side effect of Benadryl is drowsiness, which can be intensified when the drug is combined with certain medications, says Roshini Mullakary, MD, an Allergy and Immunology specialist at Northwell Health Physician Partners in Mount Kisco, NY.

“Benadryl taken by itself can cause drowsiness,” says Dr. Mullakary. “When combined with another medication that may cause sleepiness, such as Zoloft, it can cause worsening sedation.”

 is a selective serotonin reuptake inhibitor, an antidepressant commonly used to treat depression and anxiety disorders. Like Benadryl, common side effects of Zoloft include nausea, dizziness, headaches and dry mouth.

Along with increased drowsiness, individuals who take Benadryl while also on Zoloft have an increased risk of experiencing central nervous system (CNS) depression, says Stefanie Nigro, PharmD, an associate clinical professor in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy.

CNS depression is a condition caused by drugs that slow brain activity, which increases muscle relaxation and drowsiness. Signs of CNS depression can include slower heart rate and breathing, dizziness, confusion, lightheadedness, decreased consciousness and incoordination.

Benadryl itself carries a risk of CNS depression, while Zoloft has a relatively low risk, explains Dr. Nigro. “However, when the two are used in combination, the effects can be additive or enhanced,” she says.

Both Dr. Mullakary and Dr. Nigro recommend consulting with a physician before starting or combining medications.

What Is a Safer Alternative to Benadryl?

To avoid compounded drowsiness, those taking Zoloft might ask their doctors about a second-generation antihistamine for treating allergies, advises Dr. Mullakary.

“[Second-generation antihistamines] are less likely to cross the blood-brain barrier, which means they are less likely to cause sedation,” she explains. “Examples of these medications include cetirizine (Zyrtec), levocetirizine (Xyzal), fexofenadine (Allegra), loratadine (Claritin), and desloratadine (Clarinex).”

Unfortunately, second-generation antihistamines can’t treat motion sickness, Dr. Nigro clarifies. For Benadryl alternatives that fit that need, it’s best to consult a healthcare professional.

Various natural alternatives—including ginger, vitamin C and menthol—might help soothe nausea associated with motion sickness. Individuals who are prone to motion sickness might also consider preventative measures, such as avoiding greasy meals (but bringing simple foods like crackers or carbonated beverages) and hydrating before an experience that may cause the symptom.

Check out two more articles in our interaction series: Can I Take Tums with Metoprolol? and Can I Take Ibuprofen With Prednisone?