Atomoxetine and Sertraline: 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
Sertraline
No brand names on recordAtomoxetine
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.
Here's what's going on. Atomoxetine (Strattera) is cleared from your body by a liver enzyme called CYP2D6. Sertraline can slow that enzyme down. When the enzyme works slower, atomoxetine can build up in your system, and that may mean stronger effects and more side effects, like a faster heartbeat, trouble sleeping, dry mouth, stomach upset, or feeling jittery.
The good news: this is mostly a theoretical concern, not something proven to happen in everyone. Your care team can manage it easily by choosing the right atomoxetine dose for you and watching how you feel. Keep taking both as prescribed, and let your pharmacist or doctor know if you notice new or stronger side effects.
Mechanism: Sertraline is a moderate CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate (not a prodrug). Inhibition reduces atomoxetine clearance, increasing its AUC and Cmax.
Direction: Increased atomoxetine exposure, so enhanced pharmacodynamic and adverse effects (tachycardia, hypertension, insomnia, GI upset, decreased appetite).
- Evidence: theoretical; magnitude not quantified on file.
- Onset: unspecified.
- Management: if coadministration is required, atomoxetine dose may be reduced and individualized; monitor for adverse effects and hemodynamic changes. On sertraline discontinuation, an atomoxetine dose increase may be needed.
Note atomoxetine labeling already provides dosing guidance for use with strong CYP2D6 inhibitors and poor metabolizers.
What happens
Increased CYP2D6 substrate exposure
Interaction Deep Dive
Taking sertraline (which inhibits CYP2D6) alongside a CYP2D6 substrate can raise the exposure of that substrate. When the two must be given together, lower the CYP2D6 substrate dose as needed; on the other hand, discontinuing sertraline may call for raising the CYP2D6 substrate dose1.
Why it happens (mechanism)
Inhibition of CYP2D6 substrate metabolism by sertraline
How to manage this interaction
What your care team may do:
- Choose an atomoxetine dose that is right for you, since combining it with sertraline can raise atomoxetine levels. The dose may be adjusted and individualized by your care team.
- Monitor you more closely for side effects such as fast heartbeat, higher blood pressure, trouble sleeping, or reduced appetite.
- Revisit the atomoxetine dose if sertraline is ever stopped, since levels may then drop.
What you should do: Keep taking both medications exactly as prescribed. Tell your pharmacist or prescriber about any new or stronger side effects, and do not change either dose on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction studies, PARoxetine produced the following effects on medications metabolized by CYP2D6. At steady-state, PARoxetine 20 mg once daily raised the Cmax, AUC, and t(1/2) of a single 100 mg dose of desipramine by roughly 2-, 5-, and 3-fold, respectively. Among patients stabilized on risperiDONE 4 to 8 mg/day, PARoxetine 20 mg daily increased mean risperiDONE plasma concentrations by 4-fold, reduced 9-hydroxyrisperiDONE concentrations by 10%, and raised concentrations of the active moiety by 1.4-fold. In healthy volunteers who were extensive CYP2D6 metabolizers, steady-state atomoxetine AUC values were 6- to 8-fold higher and Cmax values were 3- to 4-fold higher when PARoxetine was given concomitantly compared with atomoxetine alone. Mean digoxin steady-state AUC fell by 15% when PARoxetine was present. In a study using propranolol 80 mg twice daily for 18 days, the steady-state plasma concentrations of propranolol were unchanged during coadministration with PARoxetine 30 mg once daily over the final 10 days 2.
Common questions
Can I take Atomoxetine and Sertraline together?
Sertraline can raise atomoxetine levels by slowing its breakdown, so your doctor may fine-tune your atomoxetine dose and watch for side effects. Keep taking both as prescribed and report anything new. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Atomoxetine and Sertraline 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 Atomoxetine and Sertraline interaction managed?
What your care team may do: Choose an atomoxetine dose that is right for you, since combining it with sertraline can raise atomoxetine levels. The dose may be adjusted and individualized by your care team. Monitor you more closely for side effects such as fast heartbeat, higher blood pressure, trouble sleeping, or reduced appetite. Revisit the atomoxetine dose if sertraline is ever stopped, since… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Atomoxetine or Sertraline 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 Sertraline
Keep reading about Atomoxetine
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