Do Not Take Wellbutrin SR and XL Together
You should never combine Wellbutrin SR (sustained-release) and Wellbutrin XL (extended-release) because they contain the same active ingredient—bupropion—and taking both formulations simultaneously would result in dangerous overdosing that significantly increases seizure risk. 1
Why This Combination Is Explicitly Contraindicated
The FDA drug label for bupropion explicitly warns patients that bupropion hydrochloride extended-release tablets (XL) should not be used in combination with any other medications that contain bupropion hydrochloride, including WELLBUTRIN SR (the sustained-release formulation). 1 This is not a theoretical concern—it is a direct contraindication stated in the prescribing information.
The Core Safety Issue: Dose-Related Seizure Risk
Bupropion lowers the seizure threshold in a dose-dependent manner, meaning higher total daily doses dramatically increase seizure probability. 1, 2
At the recommended maximum dose of 450 mg/day for XL or 400 mg/day for SR, the seizure incidence is approximately 0.1% (1 in 1,000 patients). 3, 4
Taking both SR and XL formulations together would push your total daily bupropion dose well above these safety limits, potentially doubling or tripling your seizure risk. 1
Understanding the Formulation Differences
All three bupropion formulations—immediate release (IR), sustained release (SR), and extended release (XL)—are bioequivalent in terms of total systemic exposure to bupropion and its active metabolites. 5, 6, 2 The key differences lie only in their release kinetics and dosing schedules:
Wellbutrin SR reaches peak concentration (Tmax) at approximately 3 hours and is dosed 150 mg twice daily (total 300 mg/day). 3, 2
Wellbutrin XL has prolonged absorption with Tmax at approximately 5 hours and is dosed 300 mg once daily. 3, 2
Both formulations deliver the same total amount of bupropion over 24 hours—they simply differ in how that dose is released. 5, 6, 2
What You Should Do Instead
If you are considering switching formulations or adjusting your regimen:
Switching Between Formulations
You can switch from SR to XL (or vice versa) at equivalent total daily doses, but you must discontinue one formulation completely before starting the other. 3
For example, if you are taking Wellbutrin SR 150 mg twice daily (300 mg total), you can switch to Wellbutrin XL 300 mg once daily—but never take both on the same day. 3
Monitor closely during the switch, as historical bioequivalence issues between brand and generic formulations have occasionally led to loss of antidepressant effect. 3
If Your Current Dose Is Inadequate
For major depressive disorder, the maximum safe dose is 400 mg/day for SR or 450 mg/day for XL—never exceed these limits. 3
If you have not achieved adequate response after 6–8 weeks at therapeutic doses, do not increase bupropion further; instead, consider augmentation with an SSRI or SNRI rather than dose escalation. 7, 3
The STAR*D trial demonstrated that augmenting an SSRI with bupropion SR (or vice versa) is equally effective as switching antidepressants, with significantly lower discontinuation rates due to adverse events (12.5% vs. 20.6% for buspirone augmentation, P < 0.001). 7, 3
Critical Safety Reminders
Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs while taking bupropion increases seizure risk—taper these substances gradually under medical supervision. 1
Screen for absolute contraindications before taking any bupropion formulation: seizure history, eating disorders (bulimia/anorexia), concurrent MAOI use, uncontrolled hypertension, or moderate-to-severe hepatic/renal impairment. 3, 1
If you miss a dose, do not double up—skip the missed dose and resume your regular schedule, as taking extra tablets to "catch up" increases seizure risk. 1