depression
14 interactions related to depression
fluoxetine + sam-e
SAM-e has independent antidepressant and serotonergic activity, and combining it with fluoxetine can additively raise serotonergic tone, increasing the risk of serotonin syndrome and hypomania. Fluoxetine's long half-life means this risk persists for weeks after the last dose.
fluoxetine + saffron
Saffron (Crocus sativus) has independent antidepressant activity, including serotonergic effects demonstrated in randomized controlled trials, and combining it with fluoxetine can theoretically add to serotonergic tone. Fluoxetine's long half-life extends the window of potential interaction for weeks after the last dose.
maoi + tyramine foods
Monoamine oxidase inhibitors block MAO-A in the gut and liver, preventing the breakdown of dietary tyramine. Unmetabolized tyramine triggers a massive release of stored norepinephrine, producing a hypertensive crisis ('cheese reaction') with severe blood pressure spikes, stroke, or death.
maoi + st. john's wort
St. John's Wort inhibits serotonin, dopamine, and norepinephrine reuptake and has weak MAOI activity in vitro. Combined with a prescription MAOI, monoamine clearance is blocked at multiple levels, producing serotonin syndrome and/or 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, intracellular and synaptic serotonin can rise to toxic levels, producing serotonin syndrome.
saffron + antidepressants
Saffron and its constituents crocin and safranal show antidepressant activity by inhibiting serotonin, norepinephrine, and dopamine reuptake and modulating monoamine oxidase, which is additive to SSRIs, SNRIs, and MAOIs and raises the theoretical risk of serotonin syndrome.
alcohol + venlafaxine
Venlafaxine (Effexor) is an SNRI that, like other antidepressants, has additive CNS-depressant effects with alcohol. The FDA-approved label warns patients to avoid alcohol because of worsening drowsiness, dizziness, impaired judgment, and the potential to aggravate the underlying mood or anxiety disorder.
alcohol + duloxetine
Duloxetine (Cymbalta) and heavy alcohol use both can damage the liver. The FDA-approved label explicitly states that Cymbalta should not be prescribed to patients with substantial alcohol use because the combination has been linked to severe, sometimes fatal, hepatotoxicity in clinical trial data.
sertraline + sam-e
SAM-e (S-adenosyl-L-methionine) has its own antidepressant and serotonergic effects, and combining it with the SSRI sertraline can additively raise serotonergic activity and increase the risk of serotonin syndrome. Case reports describe mania and serotonin-toxicity-like presentations in patients combining SAM-e with SSRIs.
bupropion + st. john's wort
Bupropion lowers the seizure threshold and St. John's wort may compound that risk, and the herb's induction of CYP enzymes (particularly the role of CYP2B6 and downstream pathways) can also alter bupropion exposure. Both also influence monoamine signaling, raising the risk of additive CNS effects.
alcohol + sertraline
Sertraline (Zoloft) and alcohol are both central nervous system depressants. Although controlled studies in healthy subjects showed sertraline did not potentiate alcohol's psychomotor impairment, the FDA label still advises against concurrent use because alcohol can worsen depression, anxiety, drowsiness, and judgment in patients being treated for mood disorders.
alcohol + fluoxetine
Fluoxetine (Prozac) and alcohol both depress the central nervous system, increasing drowsiness, dizziness, and impaired judgment. Fluoxetine and its active metabolite norfluoxetine have unusually long half-lives (1 to 4 days and 4 to 16 days), so alcohol effects can be amplified even when the drink and dose are taken hours apart.
fermented foods + maois
Fermented foods accumulate tyramine through microbial decarboxylation of tyrosine during fermentation, and MAOIs block the monoamine oxidase enzyme that normally clears tyramine from the gut and bloodstream. Unmetabolized tyramine then triggers massive norepinephrine release, which can produce a hypertensive crisis with systolic blood pressure spiking above 180 mmHg.
saffron + curcumin
Saffron (Crocus sativus) and curcumin both have antidepressant effects through complementary mechanisms: saffron modulates serotonin reuptake and increases BDNF, while curcumin reduces neuroinflammation and supports monoamine balance via MAO inhibition and HPA-axis modulation. A randomized placebo-controlled trial in major depressive disorder showed the combination was effective in reducing depressive and anxiolytic symptoms.