Sertraline and Selegiline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Selegiline
Sertraline
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines should not be taken together. Selegiline is an MAOI, and sertraline is an antidepressant that raises serotonin levels in your brain. When you combine them, serotonin can build up too high. This can cause a dangerous reaction called serotonin syndrome, with symptoms like high blood pressure, fast heartbeat, fever, sweating, shaking, muscle twitching, and confusion. In serious cases it can be life-threatening.
The good news is this is very manageable. Your care team knows to keep these two apart, and there is usually a required waiting period between them. Please talk with your doctor or pharmacist before starting, stopping, or changing either one.
Contraindicated combination. Selegiline (MAO inhibitor) plus sertraline (SSRI) produces additive serotonergic effects; MAO inhibition blocks serotonin metabolism while the SSRI blocks reuptake, risking serotonin syndrome or CNS toxicity.
- Direction: increased serotonergic activity; potentially fatal.
- Evidence: probable; serious and fatal reactions reported.
- Watch for: hypertension, tachycardia, hyperthermia, myoclonus, hyperreflexia, diaphoresis, tremor, altered mental status.
- Management: avoid co-administration. Allow at least 14 days after stopping an MAOI before starting sertraline, and at least 14 days after stopping sertraline before starting an MAOI used for psychiatric indications.
What happens
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes) or CNS toxicity
Interaction Deep Dive
Taking sertraline together with an MAOI is contraindicated. Following the discontinuation of an MAOI used to manage psychiatric conditions, allow a minimum of 14 days to pass before starting sertraline. Likewise, once sertraline has been stopped, at least 14 days should elapse before beginning treatment with an MAOI intended for psychiatric disorders1. Combining these agents, or having their therapies overlap, can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition whose manifestations include restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. There have been reports of severe reactions, some of which were fatal 3465.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of serotonin metabolism by monoamine oxidase
How to manage this interaction
The main rule here is that these two are not used at the same time. Your care team manages this by keeping a washout window between them.
- If switching from selegiline to sertraline, a wait of at least 14 days after stopping the MAOI is typically required before starting sertraline.
- If switching from sertraline to an MAOI, a wait of at least 14 days after stopping sertraline is typically required.
- Keep taking your current medicine exactly as prescribed and do not stop or start either one on your own.
Ask your pharmacist or prescriber to review your list and confirm the safe timing before any switch. Report symptoms like agitation, fever, fast heartbeat, sweating, or muscle twitching right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Using serotonin specific reuptake inhibitors together with monoamine oxidase inhibitors can result in a toxic condition called serotonin syndrome 2.
b) A 26 year old woman who had taken isocarboxazid for eight weeks discontinued the medication for 11 days before starting sertraline. Following a single 100 mg dose of sertraline, she became restless and developed twitching of the legs. She was subsequently brought to the emergency room with diaphoresis, tachycardia, hyperreflexia, and assorted neuromuscular disturbances. She showed no improvement after being treated with diazepam and propranolol. She was then administered two 4 mg doses of cyproheptadine one hour apart, with marked improvement in her symptoms following the second dose 3.
c) A drug interaction was described in a 61 year old woman when sertraline 100 mg twice daily was added to a regimen consisting of lithium, phenelzine, thioridazine, and doxepin. Three hours after her first sertraline dose, she was found in a semicomatose condition, with elevated body temperature, raised pulse, increased respiratory rate, and a blood pressure of 140/110 mmHg. After being taken to the hospital, she was initially misdiagnosed with neuroleptic malignant syndrome (NMS), a diagnosis later revised to serotonin syndrome resulting from an interaction between sertraline and phenelzine. The authors recommend that MAO inhibitor therapy be stopped for at least two weeks before starting a selective serotonin reuptake inhibitor (SSRI), and that prior to beginning a MAOI, SSRI therapy be discontinued for at least 5 half-lives of the parent drug and any active metabolites 4.
d) Two case reports pointed to a possible interaction between FLUoxetine and selegiline. In one case, a first episode of mania was seen roughly 1 month after selegiline was added to fluoxetine therapy. The patient improved 2 months after both medications were stopped, and no additional details were given. The second case involved diaphoresis, vasoconstriction, and cyanosis of the hands occurring in close temporal association with the addition of FLUoxetine and selegiline. Both drugs were stopped, with relatively rapid resolution of symptoms. Rechallenge with FLUoxetine alone took place without any incident 5.
Common questions
Can I take Sertraline and Selegiline together?
Selegiline and sertraline should not be taken together because of the risk of serotonin syndrome; a 14-day washout is needed when switching between them. Talk to your doctor or pharmacist before changing either medication. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Selegiline interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Sertraline and Selegiline interaction managed?
The main rule here is that these two are not used at the same time. Your care team manages this by keeping a washout window between them. If switching from selegiline to sertraline, a wait of at least 14 days after stopping the MAOI is typically required before starting sertraline. If switching from sertraline to an MAOI, a wait of at least 14 days after stopping sertraline is typically required.… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sertraline or Selegiline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Sternbach H: The serotonin syndrome. Am J Psychiatr 1991; 148:705-713. PubMed
- Lappin RI & Auchincloss EL: Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med 1994; 331:1021-1022. PubMed
- Graber MA, Hoehns TB, & Perry PJ: Sertraline-phenelzine drug interaction: a serotonin syndrome reaction. Ann Pharmacother 1994; 28:732-735. DOI
- Suchowersky O & de Vries JD: Interaction of fluoxetine and selegiline (letter). Can J Psychiatry 1990; 35:571-572. PubMed
- Bhatara VS & Bandettini FC: Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993; 12:222-225.
Keep reading about Selegiline
Keep reading about Sertraline
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