Sertraline and Aripiprazole: 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
Aripiprazole
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.
Aripiprazole (Abilify) and sertraline (Zoloft) are often prescribed together, but there are two things worth knowing. First, both can slightly affect your heart's rhythm (something called QT prolongation). Second, sertraline slows down a liver enzyme that clears aripiprazole, so the aripiprazole level in your body can climb higher, which may bring more side effects like drowsiness, restlessness, or shakiness.
The good news: this combo is used successfully all the time. Your care team can pick the right aripiprazole dose for you and keep an eye on how you feel. Please don't stop or change either medicine on your own, just talk with your doctor or pharmacist about any concerns.
Effect: Additive QTc prolongation plus increased aripiprazole exposure. Sertraline is a moderate CYP2D6 inhibitor; aripiprazole is a CYP2D6 (and CYP3A4) substrate, so inhibition raises aripiprazole AUC/Cmax and increases dose-related adverse effects. Both agents independently prolong QTc.
- Direction: Increased aripiprazole effect/toxicity; increased arrhythmia risk.
- Severity/evidence: Major; probable.
- Onset: Unspecified.
- Management: Consider reduced aripiprazole dosing (per labeling, roughly halve when a strong CYP2D6 inhibitor is present); dose is individualized. Monitor ECG/QTc and electrolytes in at-risk patients, watch for EPS/akathisia/sedation, and re-evaluate dose if sertraline is stopped.
What happens
Increased risk of QT interval prolongation and an increased CYP2D6 substrate exposure
Interaction Deep Dive
Do not combine sertraline, which acts as both a CYP2D6 inhibitor and an agent that prolongs the QT interval, with medications that are QT prolonging substrates of CYP2D6. When drugs that lengthen the QTc interval are taken together, the likelihood of QTc prolongation and/or ventricular arrhythmias rises. It may be necessary to lower the dose of the CYP2D6 substrate. On the other hand, should sertraline be stopped, the dosage of the CYP2D6 substrate may need to be raised1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP2D6-substrate metabolism by sertraline
How to manage this interaction
This pairing is common and manageable when your care team tailors it to you.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your aripiprazole dose may need to be adjusted and individualized by your care team because sertraline can raise its level.
- Your team may monitor you more closely, which can include checking your heart rhythm (ECG) and electrolytes, especially if you have heart concerns.
- Tell your doctor or pharmacist if you notice fainting, palpitations, severe dizziness, unusual restlessness, or heavy drowsiness.
- If sertraline is ever stopped, remind your prescriber, as the aripiprazole dose may need adjusting again.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When risperiDONE 4 to 8 mg/day (a CYP2D6 substrate) was given together with PARoxetine 20 mg/day, its mean plasma concentrations rose by roughly 4-fold 2.
Common questions
Can I take Sertraline and Aripiprazole together?
Taking aripiprazole with sertraline can raise aripiprazole levels and add to heart-rhythm (QT) risk, so your care team may adjust the aripiprazole dose and monitor you; keep taking both as prescribed and report fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Aripiprazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Aripiprazole interaction managed?
This pairing is common and manageable when your care team tailors it to you. Keep taking both as prescribed unless your prescriber tells you otherwise. Your aripiprazole dose may need to be adjusted and individualized by your care team because sertraline can raise its level. Your team may monitor you more closely, which can include checking your heart rhythm (ECG) and electrolytes, especially if y… 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 Aripiprazole 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 (2)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.
Keep reading about Aripiprazole
Keep reading about Sertraline
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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