serotonin syndrome
23 interactions related to serotonin syndrome
adderall + st. john's wort
Adderall (mixed amphetamine salts) raises synaptic norepinephrine, dopamine, and to a lesser extent serotonin. St. John's Wort inhibits reuptake of those same monoamines. Together they can push the serotonergic system far enough to risk serotonin syndrome and can add cardiovascular strain. Separately, St. John's Wort strongly induces the CYP3A4 enzyme and P-glycoprotein, which can blunt the effect of many co-taken medicines.
methylphenidate + st. john's wort
Methylphenidate treats ADHD by inhibiting reuptake of dopamine and norepinephrine. St. John's Wort adds its own monoamine reuptake activity and is a strong inducer of the CYP3A4 drug-metabolising enzyme. A small published observation suggests St. John's Wort can blunt methylphenidate's effect on ADHD symptoms. There is also a theoretical, additive serotonergic risk, mainly relevant if other serotonergic drugs are present, but no confirmed serotonin syndrome cases have been reported for this specific pair.
sertraline + st. john's wort
Sertraline is an SSRI that blocks serotonin reuptake, and St. John's wort independently raises central serotonin through constituents such as hyperforin and hypericin. Combining them can trigger serotonin syndrome, a potentially life-threatening reaction marked by altered mental status, autonomic instability, and neuromuscular hyperactivity. St. John's wort also induces CYP3A4 and CYP2C19, which can lower sertraline levels and undermine treatment.
sertraline + 5-htp
Sertraline blocks serotonin reuptake and 5-HTP (5-hydroxytryptophan) is the immediate precursor of serotonin, so it directly increases serotonin synthesis. Combining the two stacks production and reuptake blockade, which can precipitate serotonin syndrome.
fluoxetine + sam-e
SAM-e has its own serotonergic and mood-elevating activity, so combining it with fluoxetine can add to your overall serotonin tone. In theory this can raise the risk of serotonin syndrome, and in vulnerable people it can tip mood into hypomania or mania. Because fluoxetine clears slowly, this caution lingers for weeks after the last dose. The evidence is mostly case reports involving other antidepressants and general guidance about combining SAM-e with serotonin-raising drugs, rather than fluoxetine-specific data.
duloxetine + st. john's wort
Duloxetine and St. John's wort both increase serotonergic activity, and combining them can raise serotonin to levels associated with serotonin syndrome.
fluoxetine + tryptophan
Fluoxetine blocks serotonin reuptake while tryptophan supplies the raw material for serotonin synthesis, and the combination can produce an excitatory reaction or serotonin syndrome. Fluoxetine's long-acting active metabolite means this risk persists for weeks after the last dose.
fluoxetine + st. john's wort
Fluoxetine and St. John's wort both increase serotonin activity, and combining them can add to the same effect and contribute to serotonin syndrome.
tramadol + st. john's wort
Tramadol inhibits serotonin and norepinephrine reuptake, and St. John's Wort increases central serotonergic activity, so combining them can add together and raise the risk of serotonin syndrome. St. John's Wort also induces CYP3A4 and CYP2B6, enzymes involved in tramadol metabolism, which may lower levels of tramadol's active M1 metabolite and weaken pain relief.
maoi + st. john's wort
St. John's Wort raises brain serotonin, norepinephrine, and dopamine through reuptake inhibition and shows weak monoamine oxidase inhibition. Layered on a prescription MAOI, which blocks the breakdown of those same monoamines, the combination can push monoamine signaling to dangerous levels and is contraindicated because of the risk of serotonin syndrome and hypertensive crisis.
maoi + 5-htp
5-HTP is the direct precursor to serotonin and bypasses the rate-limiting step of serotonin synthesis. Combined with an MAOI, which blocks serotonin breakdown, serotonin can rise to dangerous levels and trigger serotonin syndrome, a potentially life-threatening reaction.
paroxetine + st. john's wort
Paroxetine is an SSRI that raises serotonin by blocking its reuptake. St. John's wort independently raises serotonin and also induces drug-metabolizing enzymes and P-glycoprotein. Taken together, the additive serotonin effect can precipitate serotonin syndrome, and paroxetine is among the most frequently implicated SSRIs in published St. John's wort case reports.
amitriptyline + st. john's wort
St. John's wort induces the cytochrome P450 enzymes (and the P-glycoprotein transporter) that clear amitriptyline, measurably lowering amitriptyline blood levels and reducing its antidepressant and pain-relieving effect. Because both also raise serotonin signaling, combining them adds a theoretical risk of serotonin syndrome. The net effect can be a weaker antidepressant plus an added safety concern.
venlafaxine + st. john's wort
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). St. John's wort independently inhibits serotonin (and to a lesser extent norepinephrine and dopamine) reuptake. Combining them can drive synaptic serotonin higher and trigger serotonin syndrome, and St. John's wort can also reduce venlafaxine exposure by inducing drug-metabolizing enzymes such as CYP3A4.
trazodone + 5-htp
Both trazodone and 5-HTP raise serotonin activity, but through different routes. Trazodone is a serotonin antagonist and reuptake inhibitor that keeps more serotonin in the synapse, while 5-HTP is a direct precursor that increases how much serotonin the body makes. Stacking the two adds up, and major drug-interaction databases flag the pairing as a serious interaction because of the risk of serotonin syndrome.
alcohol + tramadol
Tramadol combined with alcohol produces additive central nervous system and respiratory depression, and the combination lowers the seizure threshold, increasing the risk of convulsions, serotonin-related reactions, and life-threatening overdose. Tramadol's serotonergic and noradrenergic activity makes this pairing more hazardous than alcohol with a typical opioid.
sertraline + sam-e
SAM-e (S-adenosyl-L-methionine) has its own antidepressant and serotonergic activity, so combining it with the SSRI sertraline can add serotonergic effects on top of each other. Case reports describe serotonin-toxicity-like presentations and treatment-emergent mania in patients combining SAM-e with serotonergic antidepressants.
cannabis + ssris
Cannabinoids inhibit liver enzymes (including CYP2C19) that clear several SSRIs such as sertraline, citalopram, and escitalopram, which can raise SSRI plasma levels. Cannabinoids also touch the serotonin system, and case reports describe serotonin syndrome precipitated by high-potency cannabis in patients on serotonergic regimens.
fluoxetine + 5-htp
Fluoxetine is an SSRI that blocks serotonin reuptake, and 5-HTP is a direct precursor the body converts into serotonin. Combining them can push serotonin to levels associated with serotonin syndrome, and fluoxetine's long-lived active metabolite norfluoxetine extends this risk for weeks after the last dose.
tramadol + 5-htp
Tramadol blocks the reuptake of serotonin, and 5-HTP is a direct precursor that raises serotonin production in the brain. Stacking the two can push serotonin activity too high and trigger serotonin syndrome, a potentially life-threatening reaction.
escitalopram + st. john's wort
Escitalopram is a selective SSRI cleared mainly by CYP2C19 and CYP3A4. St. John's wort independently raises serotonin tone and is a strong inducer of those same enzymes and P-glycoprotein. Taken together, the combination can add to serotonergic effects and, through enzyme induction, lower escitalopram levels and blunt its antidepressant effect. Documented serotonin syndrome cases with St. John's wort involve other SSRIs rather than escitalopram specifically, so the combination is best avoided rather than treated as a guaranteed emergency.
sertraline + tryptophan
Sertraline is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin signaling, and L-tryptophan is the dietary precursor your body converts into serotonin. Taking them together can push serotonergic activity too high, raising the risk of serotonin syndrome (agitation, tremor, sweating, fast heart rate, and in severe cases fever, rigidity, and seizures).
cacao + maois
Raw or ceremonial cacao carries a somewhat higher load of biogenic amines such as tyramine than fully processed chocolate. Dietary analyses show that the tyramine content of cocoa and chocolate is generally low, and there is no documented human case of a hypertensive crisis from cacao on a monoamine oxidase inhibitor (MAOI). The sensible approach is moderation with raw or ceremonial cacao rather than blanket avoidance, reviewed with your prescriber.