Combination

Mixing Diphenhydramine and SSRIs

DeliriantAntidepressant
Diphenhydramine also called
benadryl, dph, sleep aid, zzzquil, unisom
SSRIs also called
ssri, zoloft, sertraline, lexapro, escitalopram, prozac
Verdict

Dangerous

There is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The combination may increase each other's side effects, such as dizziness and drowsiness.

Risk / Physical + headspace

This combination carries bodily risk and can go badly psychologically. The headspace part often arrives first and makes the physical part harder to notice.

Can you mix Diphenhydramine and SSRIs?

High risk of death or life-changing injury. Do not combine.

Source

TripSit drug combination chart, retrieved 2026-08-20. View the dataset.

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Rated dangerous. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.