Can You Take Benadryl And Paxil Together?

In our latest question and answer, the pharmacist discusses whether or not there is a drug interaction between Paxil (paroxetine) and Benadryl (diphenhydramine).

Apr 09, 2018

Bryan asked

Can you take Benadryl and Paxil together? I have been on Paxil for years and need to take Benadryl to sleep. I can't find any problem with the two medications online but just wanted to check.


There is not a drug interaction between Benadryl (diphenhydramine) and Paxil (paroxetine). However, using both medications together can increase the risk of sedation and drowsiness.

Therefore, due to the risk of additive sedation, the combination should be used with caution. In most cases, Benadryl administration should only be done in the evening.

Paxil (Paroxetine)

Paxil (paroxetine) is classified as a selective serotonin re-uptake inhibitors (SSRI), indicated for the treatment of major depressive disorder.

There is a small risk of sedation and cognitive impairment with the use of SSRI medications, including Paxil.

According to the package insert for Paxil, drowsiness occurred in 9-24% of individuals during clinical trials. Other cognitive effects, such as altered concentration and memory impairment can have occurred as well, but far less often.

Benadryl (Diphenhydramine)

Benadryl (diphenhyramine) is a first-generation antihistamine, which are associated with prounounced sedation and drowinsess. Benadryl, in addition to its use for allergies, is commonly used as a nighttime sleep aide.

Caution is always advised when combining Benadryl with other medications that can cause sedation due to the risk of additive effects.

Paxil - Benadryl Information

Since SSRIs, like Paxil, are associated with a low potential of cognitive impairment, caution is advised when using with CNS depressants or other medications that cause sedation, like Benadryl (diphenhyramine).

In those who tolerate Paxil well, and do not become sedated by it, use of Benadryl should be safe.

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