antidepressant
20 interactions related to antidepressant
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.
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.
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.
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.
saffron + antidepressants
Saffron's active constituents (crocin and safranal) show antidepressant-like activity in laboratory and animal studies, partly through monoamine reuptake and monoamine-oxidase inhibition. This overlaps with how SSRIs, SNRIs, and MAOIs work, raising a theoretical concern about additive serotonergic effects. In practice, human trials combining standardized saffron with fluoxetine or sertraline reported no serotonin syndrome and no serious adverse events, and there are no documented human cases from this combination.
alcohol + venlafaxine
Venlafaxine (Effexor) is an SNRI antidepressant, and alcohol is a central nervous system depressant. The FDA-approved label advises avoiding alcohol because the combination can add to drowsiness and dizziness and can worsen the mood or anxiety disorder being treated. The concern is about additive sedation, blood pressure, and undermined treatment rather than a dramatic pharmacokinetic clash, which is why it is rated moderate.
alcohol + duloxetine
Duloxetine (Cymbalta) can occasionally cause liver injury, and its FDA label advises against prescribing it to people with substantial or chronic alcohol use or existing liver disease, because both substances stress the liver. Documented cases have generally been reversible after stopping the drug, with no clear pattern of alcohol-linked liver failure in the published case series.
alcohol + amitriptyline
Amitriptyline is a sedating tricyclic antidepressant with strong antihistaminic and anticholinergic effects. Combining it with alcohol — also a central nervous system depressant — produces additive drowsiness, impaired coordination and reaction time, and a greater risk of falls and accidents. The FDA label warns explicitly that amitriptyline may enhance the response to alcohol.
alcohol + trazodone
Trazodone and alcohol both depress the central nervous system, producing additive sedation, dizziness, orthostatic hypotension, and impaired coordination. The FDA label states trazodone may enhance the response to alcohol, and combining the two raises the risk of falls and accidents. Rarely, trazodone is associated with QT prolongation, orthostatic syncope, and priapism.
alcohol + mirtazapine
Mirtazapine and alcohol both depress the central nervous system, producing additive sedation, drowsiness, and impaired coordination and judgment. Mirtazapine's strong H1-antihistamine activity makes the sedative interaction with alcohol particularly pronounced, and the FDA label specifically advises avoiding alcohol during treatment.
caffeine + sertraline
Caffeine and sertraline do not share a receptor, but their side-effect profiles overlap. Both can cause anxiety, jitteriness, insomnia, stomach upset and headache, so these symptoms can stack — most noticeably during the first few weeks of sertraline treatment. Unlike fluvoxamine, sertraline does not meaningfully slow caffeine clearance.
cbd + sertraline
CBD inhibits CYP2C19, one of several enzymes that help break down sertraline, so adding CBD can raise sertraline exposure. A single published case report describes low sodium (hyponatremia) and cognitive decline in an older intermediate-metabolizer patient who added over-the-counter CBD to long-standing sertraline. The evidence is limited to this one report, so treat it as a reason for caution and prescriber discussion rather than a strong contraindication.
coffee + sertraline
Sertraline is a weak inhibitor of CYP1A2, the enzyme that clears caffeine, so it can slow caffeine metabolism mildly. More relevant in practice, caffeine can add to the jitteriness, palpitations, anxiety, and insomnia that often appear in the first weeks of sertraline. The pharmacokinetic effect is far smaller than with fluvoxamine and is usually minor.
alcohol + sertraline
Sertraline (Zoloft) and alcohol both act on the central nervous system. Controlled studies in healthy volunteers did not show sertraline worsening alcohol's effects on thinking or coordination, but the FDA label still advises against drinking on sertraline because alcohol can deepen depression and anxiety, worsen drowsiness and sleep, and blunt the medication's benefit in people being treated for a mood disorder.
alcohol + fluoxetine
Fluoxetine (Prozac) is an SSRI antidepressant, and alcohol is a central nervous system depressant. The FDA-approved Prozac label states that alcohol use is not recommended while taking fluoxetine. Fluoxetine and its active metabolite norfluoxetine also have unusually long half-lives, so the drug stays in your system for weeks once you reach steady state — there is no simple "timing window" that avoids the interaction. Notably, a controlled human study found that alcohol did not measurably increase fluoxetine's psychomotor impairment, so the combined sedative effect is more modest than once assumed; the precaution remains sensible but is not an 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).
saffron + curcumin
Saffron (Crocus sativus) and curcumin (from turmeric) both have antidepressant effects through partly complementary mechanisms: saffron modulates serotonin and dopamine reuptake and increases BDNF, while curcumin reduces neuroinflammation, supports monoamine balance, and normalizes the HPA axis. A randomized, double-blind, placebo-controlled trial found a saffron plus curcumin combination significantly improved depressive symptoms versus placebo in adults with major depression.