Sertraline: Drug Interactions

Major Interactions — Avoid or Monitor Closely

• ⚠MAOIs (irreversible and reversible) — risk of life-threatening serotonin syndrome; 14-day washout required between MAOI and SSRI (5 weeks for fluoxetine after stopping it)
• ⚠Linezolid / IV methylene blue — monoamine oxidase inhibition → serotonin syndrome risk
• ⚠Other serotonergic agents (tramadol, triptans, pethidine, St. John's Wort) — additive serotonin syndrome risk

Moderate Interactions — Use With Caution

• •Warfarin / anticoagulants — SSRIs inhibit platelet aggregation; combined use increases bleeding risk 3–15×
• •NSAIDs — combined use increases upper GI bleeding risk; consider PPI co-prescription
• •Tricyclic antidepressants — CYP2D6 inhibition by fluoxetine/paroxetine raises TCA levels
• •Antipsychotics (haloperidol, risperidone) — CYP2D6 inhibition increases plasma levels
• •Lithium — augmentation strategy but requires monitoring for serotonin syndrome and toxicity
• •Benzodiazepines — additive CNS depression; fluvoxamine markedly elevates diazepam levels via CYP3A4

Food & Drink Interactions

• •Grapefruit juice — modest CYP3A4 inhibition; most relevant for high-dose fluvoxamine/escitalopram
• •Alcohol — additive CNS depression; impairs cognitive function and coordination
• •High-tyramine foods — not contraindicated (unlike MAOIs) unless co-prescribed with MAOI

Monitoring Requirements

Bleeding risk in anticoagulated patients; serotonin syndrome signs when combining serotonergic agents; QTc interval with citalopram/escitalopram (dose-dependent QTc prolongation above 40mg/20mg respectively); sodium in elderly (SIADH risk)