Substance
What not to mix with SSRIs (antidepressants)
AntidepressantDrug class
Also calledssri, zoloft, sertraline, lexapro, escitalopram, prozac
Summary
SSRIs is checked against 40 other substances — 5 dangerous, 1 unsafe and 9 caution.
Dangerous
5- SSRIs and AMTHigh risk of death or life-changing injury. Do not combine.
- SSRIs and DiphenhydramineAt recreational doses of diphenhydramine this carries a high risk of serotonin syndrome. Do not combine at recreational doses.
- SSRIs and DXMTogether they carry a high risk of serotonin syndrome. Do not combine.
- SSRIs and MAOIsHigh risk of death or life-changing injury. Do not combine.
- SSRIs and TramadolHigh risk of death or life-changing injury. Do not combine.
Unsafe
1Caution
9- SSRIs and AlcoholAlcohol can hit harder than usual on an SSRI, dulling judgement and coordination more. Drink less than you normally would.
- SSRIs and CodeineSome SSRIs stop codeine working, which tempts redosing, and if the SSRI changes, the same dose can hit far harder. Do not redose to chase the effect.
- SSRIs and IbuprofenTogether they raise the risk of stomach bleeding. If you take an SSRI daily and use ibuprofen often, raise it with your prescriber.
- SSRIs and KratomSome SSRIs raise kratom levels, so your usual dose can hit harder, and serotonin syndrome is possible. Take less kratom than usual.
- SSRIs and MephedroneSSRIs blunt mephedrone, which tempts redosing, and redosing is what raises the serotonin syndrome risk. Do not redose to chase the effect.
- SSRIs and MethadoneSome SSRIs raise methadone levels and can add to its effect on heart rhythm. Talk to whoever prescribes either, rather than stopping them.
- SSRIs and MethamphetamineSSRIs blunt meth, which tempts redosing, while adding serotonin syndrome risk, and some make meth last longer. Do not redose to chase the effect.
- SSRIs and MXEDepending on the SSRI, this can be unpredictable. Take less MXE than usual, and do not use alone.
- SSRIs and PregabalinTogether they cause more drowsiness and dizziness than people expect from two prescriptions. Expect to be more impaired than on either alone.
Low / synergy
1Low / decrease
10Low / no synergy
14Checking more than one?
This page rates SSRIs against one substance at a time. Combinations of three or more carry risks that no pair-by-pair list can show — the checker rates every pair at once and flags the whole-mix ones on top.
Open SSRIs in the checkerOther antidepressants
All combinations →Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety. Combination data from the TripSit drug combination chart, retrieved 2026-08-20.