Mixing SSRIs (antidepressants) and Tylenol PM
Dangerous
High risk of death or life-changing injury. Do not combine.
What 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 take SSRIs with Tylenol PM?
Tylenol PM contains acetaminophen and diphenhydramine. The most concerning part is SSRIs with Tylenol PM (Diphenhydramine): at recreational doses of diphenhydramine this carries a high risk of serotonin syndrome. Do not combine at recreational doses. MixSafe rates SSRIs with Tylenol PM as "Dangerous" — high risk of death or life-changing injury. Do not combine. Sources: the Drug Facts labels on DailyMed, the TripSit combination chart and MixSafe research. Educational information, not medical advice.
What is in it
- Tylenol PM
- Acetaminophen + Diphenhydramine.
Ingredient by ingredient
SSRIs + Tylenol PM (Diphenhydramine)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.
Source: TripSit drug combination chart
SSRIs + Tylenol PM (Acetaminophen)Low risk, no synergy
Neither substance is expected to meaningfully change the other. Both still carry their own individual risks.
No specific interaction is documented. Acetaminophen's main risk is dose-dependent liver injury, so the thing to watch in any combination is total daily intake across all products (roughly 4g/24h) and anything else straining the liver.
Sources: Prescott LF. Paracetamol, alcohol and the liver. Br J Clin Pharmacol. 2000 · Acetaminophen: A Liver Killer or Thriller
- Tylenol PM Extra Strength, Drug Facts label. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce58105b-f010-47af-8f31-6dd4ce4e9cba
Ingredient lists checked 2026-09-27. Formulas change and store brands differ, so the Drug Facts box on your own packet is the final word.
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