Risk of Seizure with Wellbutrin and TMS Combination
The combination of bupropion (Wellbutrin) and TMS theoretically increases seizure risk, and bupropion should be used with extreme caution or avoided during TMS treatment, particularly in patients with any additional seizure risk factors. 1
Understanding the Theoretical Risk
Why This Combination Raises Concern
Bupropion independently lowers the seizure threshold, with a baseline seizure risk of approximately 0.1% at therapeutic doses for smoking cessation and 0.35-0.48% at doses ≤450 mg/day for depression. 1, 2, 3
TMS safety guidelines are fundamentally based on minimizing seizure risk, with an overall TMS-related seizure incidence of <1%. 1, 4
The 2019 Neuroscience and Biobehavioral Reviews consensus explicitly identifies bupropion as a factor that can theoretically increase brain sensitivity to TMS-induced seizures, stating that "any factor that independently increases the risk of a seizure (e.g., cocaine use, alcohol withdrawal, benzodiazepine/barbiturate use/withdrawal in opioid use, tramadol use, bupropion in nicotine treatment) can, in theory, increase brain sensitivity to TMS induced seizures." 1
The Evidence Gap
There is currently no direct evidence documenting increased serious adverse events from combining bupropion with TMS, but this reflects limited data rather than proven safety. 1
The consensus guidelines emphasize that "increased vigilance is always warranted when theoretical concerns exist or in specific patient subgroups with limited prior data." 1
Clinical Decision-Making Algorithm
When to Absolutely Avoid This Combination
Do NOT combine bupropion with TMS if the patient has:
History of seizures or seizure disorder - both bupropion and TMS should be avoided independently in these patients. 1, 2
Brain metastases or structural brain lesions - bupropion is contraindicated in this population regardless of TMS. 1
History of head trauma - this was present in over half of reported bupropion-related seizure cases. 5
Eating disorders - predisposing factor for bupropion-induced seizures. 5
Alcohol abuse or active withdrawal - compounds seizure risk from both interventions. 1, 5
Concurrent medications that lower seizure threshold (benzodiazepines, tramadol, other stimulants). 1, 5
When Extreme Caution May Allow Combination
If proceeding despite theoretical risk, implement ALL of the following:
Use the lowest effective bupropion dose - start at 150 mg once daily and titrate slowly; never exceed 300 mg/day when combined with TMS (well below the 450 mg/day maximum). 5, 2
Ensure stable bupropion dosing for at least 2 weeks before initiating TMS to avoid the higher-risk titration period. 2
Use conservative TMS parameters - lower intensity, fewer pulses per session, and longer inter-train intervals than standard protocols. 1
Implement enhanced safety monitoring including detailed seizure history screening and consideration of baseline EEG if any borderline risk factors exist. 1
Obtain explicit informed consent documenting the theoretical additive seizure risk. 1
Dose-Dependent Considerations
Bupropion's seizure risk is clearly dose-dependent, with risk increasing substantially above 450 mg/day (the maximum recommended dose). 5, 3, 6
When combined with TMS, consider 300 mg/day as the practical maximum to maintain an adequate safety margin. 5, 2
For patients with hepatic impairment, limit to 150 mg/day total regardless of formulation when considering TMS combination. 5
For renal impairment, reduce dose by half (e.g., maximum 150-225 mg/day if combining with TMS). 5
Practical Management Approach
Preferred Strategy
The safest approach is to discontinue bupropion before initiating TMS, allowing a washout period of at least 5 half-lives (approximately 5-7 days for immediate-release, longer for extended-release formulations). 1
If Continuation is Deemed Necessary
Document clear rationale for why bupropion cannot be discontinued or substituted with an alternative antidepressant. 1
Screen rigorously for ALL predisposing factors - over half of bupropion-related seizures occurred in patients with identifiable risk factors. 5, 3
Consider alternative antidepressants that do not lower seizure threshold (SSRIs, SNRIs other than venlafaxine at high doses). 1
Monitoring During Combined Treatment
Observe the patient for at least 30 minutes post-TMS session for any signs of seizure activity or post-ictal symptoms. 4
Educate patients on seizure warning signs and provide clear instructions to report any unusual neurological symptoms immediately. 1, 4
If a seizure occurs, it will likely be self-limiting, but TMS should be discontinued and the risk-benefit ratio reassessed before any consideration of continuation. 4
Key Caveats
The absence of reported cases does not equal safety - this combination has likely been used infrequently, limiting available safety data. 1
Individual seizure thresholds vary widely, and some patients may tolerate this combination while others may not. 3, 6
The overall risk remains low but non-zero - both interventions independently carry <1% seizure risk, but the combined risk is unknown and theoretically additive. 1, 4