Selegiline + Sertraline
STOP — Contraindicated
FDA contraindication — do not use together. 14-day washout after stopping selegiline before starting SSRI (and vice versa).
Evidence level: STRONG
What this interaction means
Selegiline (Eldepryl, Emsam) and sertraline (Zoloft) must not be used together. Selegiline is an MAO inhibitor used for Parkinson disease, and combining it with an SSRI can cause dangerous serotonin syndrome.
How it works (mechanism)
Selegiline is an irreversible MAO-B inhibitor (at recommended doses). Combined with SSRI serotonin reuptake inhibition, severe serotonin syndrome risk. FDA labels for both drugs warn against this combination.
Practical advice
A 14-day washout period is required when switching between these medications. Tell all your doctors about every medication you take.
Timing
Take Sertraline at the same time each day — morning is most common to avoid sleep disruption. Selegiline follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Risk factors
Higher risk for: elderly, those on multiple serotonergic drugs, people with liver impairment, CYP2D6 poor metabolizers, recent dose changes, or concurrent use of MAOIs or triptans.
Symptoms to watch for
High fever, muscle rigidity, rapid heart rate, blood pressure instability, agitation, confusion, seizures
What to tell your doctor
Discuss 14-day washout protocol. Ask about depression treatment options compatible with MAO inhibitor therapy.
Safer alternatives
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
Frequently asked questions
Can I take Selegiline and Sertraline together?
Selegiline (Eldepryl, Emsam) and sertraline (Zoloft) must not be used together. Selegiline is an MAO inhibitor used for Parkinson disease, and combining it with an SSRI can cause dangerous serotonin syndrome.
When should I take Selegiline vs Sertraline?
Take Sertraline at the same time each day — morning is most common to avoid sleep disruption. Selegiline follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
What symptoms should I watch for if I combine Selegiline and Sertraline?
High fever, muscle rigidity, rapid heart rate, blood pressure instability, agitation, confusion, seizures
Are there safer alternatives to combining Selegiline with Sertraline?
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
What should I tell my doctor about taking Selegiline and Sertraline?
Discuss 14-day washout protocol. Ask about depression treatment options compatible with MAO inhibitor therapy.
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