Mixing Diphenhydramine (Benadryl) and SSRIs (antidepressants)
Dangerous
At recreational doses of diphenhydramine this carries a high risk of serotonin syndrome. Do not combine at recreational doses.
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.
This combination carries bodily risk and can go badly psychologically. The headspace part often arrives first and makes the physical part harder to notice.
Headspace vs physical riskWhat to do
- Say what was taken and how much.Responders need it, and in most US states Good Samaritan laws protect both of you from drug possession charges when you call for an overdose.
- Unresponsive: put them on their side, tilt the head back, and stay until help arrives.Never leave someone alone to “sleep it off”.
- Never Use Alone 1-800-484-3731Stays on the line and sends help if you stop responding.
- Full steps: what to do if it is already happeningOverdose signs, the recovery position, what to say on the call, and whether you can be charged for making it.
- Poison Control 1-800-222-1222Free and 24/7, for “is this bad?” before it becomes an emergency.
Can you mix Diphenhydramine (Benadryl) and SSRIs (antidepressants)?
MixSafe rates mixing Diphenhydramine and SSRIs as "Dangerous" — high risk of death or life-changing injury. Do not combine. Source: TripSit drug combination chart, retrieved 2026-08-20. Educational information, not medical advice.
- Diphenhydramine also called
- benadryl, dph, sleep aid, zzzquil, unisom, doxylamine
- SSRIs also called
- ssri, zoloft, sertraline, lexapro, escitalopram, prozac
TripSit drug combination chart, retrieved 2026-08-20. View the dataset.
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Checking more than two?
Combinations of three or more carry risks that no pair-by-pair chart can show. The checker rates every pair at once and flags the whole-mix ones on top.
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Rated dangerous. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.