Bupropion raises the level of other antidepressants, antipsychotics and beta blockers by blocking CYP2D6
The Wellbutrin XL label: "Bupropion inhibits CYP2D6 and can increase concentrations of" antidepressants such as venlafaxine, nortriptyline, paroxetine and sertraline, antipsychotics such as haloperidol and risperidone, and metoprolol.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The label lists examples, not a closed list; the size of the concentration increase varies by drug and is not given in the summary section read.
Bupropion is often added to another antidepressant, which is exactly the situation its interaction section is about.
Significant findings
WELLBUTRIN XL prescribing information (Bausch Health, February 2026), Drug Interactions summary: "Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Consider dose reduction when using with bupropion."
The other direction: "CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin)".
Three more lines from the same summary: "Drugs that lower seizure threshold: Dose Wellbutrin XL with caution." "Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly". "MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with Wellbutrin XL."
And one that is not a drug interaction but is worth knowing: "False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion."
Worth asking
The combination of bupropion with an SSRI or SNRI is common and often sensible; the label does not forbid it, it asks for a dose review of the other drug. The seizure line is the one to take seriously if you are also on tramadol, a stimulant or an antipsychotic, or drink heavily. If bupropion is being added to your regimen, the questions are whether any of your other drugs is on the CYP2D6 list and whether anything else you take lowers the seizure threshold.
Source
WELLBUTRIN XL (bupropion hydrochloride) extended-release tablets: FDA-approved prescribing information, Drug Interactions 7.1 to 7.7 — Bausch Health US LLC; US Food and Drug Administration (2026)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- Industry funded
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: The label lists examples, not a closed list; the size of the concentration increase varies by drug and is not given in the summary section read. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
WELLBUTRIN XL (bupropion hydrochloride) extended-release tablets: FDA-approved prescribing information, Drug Interactions 7.1 to 7.7 — Bausch Health US LLC; US Food and Drug Administration (2026). Published in: Regulator or national health body. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Regulatory safety determination. Funding: Industry funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.