Substance
What not to mix with SSRIs
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 DiphenhydramineThere is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The…
- SSRIs and DXMHigh risk of serotonin syndrome.
- 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 may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system…
- SSRIs and CodeineFluoxetine and paroxetine strongly inhibit CYP2D6, the enzyme that turns codeine into morphine. The usual result is that codeine stops working, which…
- SSRIs and IbuprofenSSRIs deplete platelet serotonin and impair clotting; NSAIDs damage the gastric mucosa. Combined, they measurably increase the risk of upper…
- SSRIs and KratomTwo problems at once. Several SSRIs inhibit CYP2D6, which shifts how mitragynine is cleared and can raise levels from an unchanged dose. Kratom is…
- SSRIs and MephedroneSSRIs blunt mephedrone's effects (which invites redosing) while raising serotonin syndrome risk. The blunting is the more common outcome; the…
- SSRIs and MethadoneSeveral SSRIs inhibit the enzymes that clear methadone, raising levels from an unchanged dose, and some independently prolong the QT interval that…
- SSRIs and MethamphetamineSSRIs blunt methamphetamine's effect, which invites redosing, while adding serotonin toxicity risk. Some SSRIs also inhibit CYP2D6 and slow its…
- SSRIs and MXEDepending on the SSRI this combination can be unpredictable
- SSRIs and PregabalinAdditive sedation and dizziness. No serotonergic interaction, but the combined impairment is more than people expect from a prescribed pair.
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.