What should be done for a patient with a history of Attention Deficit Hyperactivity Disorder (ADHD) and depression, who recently started taking Wellbutrin (bupropion) and is now experiencing seizure-like activity?

Immediate Discontinuation of Wellbutrin Required

Discontinue bupropion (Wellbutrin) immediately and permanently if seizure-like activity has occurred—this is an absolute contraindication to continued use. 1

Immediate Management Steps

Stop the medication now. The FDA drug label explicitly states: "Discontinue bupropion hydrochloride extended-release tablets (XL) and do not restart treatment if the patient experiences a seizure." 1 This is not negotiable—bupropion lowers seizure threshold through its effects on dopaminergic, adrenergic, and nicotinic acetylcholinergic receptor systems. 2

Critical Actions Within 24-48 Hours

• Obtain emergency neurological evaluation to confirm whether true seizure activity occurred versus other neuropsychiatric symptoms (agitation, tremor, myoclonus). 1, 3
• Order baseline EEG if seizure is confirmed, as bupropion-induced seizures can show EEG abnormalities that typically resolve within 2-4 weeks. 4, 3
• Review complete medication list for other seizure threshold-lowering agents (antipsychotics, tricyclic antidepressants, theophylline, systemic corticosteroids, other stimulants). 1
• Assess for recent discontinuation of alcohol, benzodiazepines (including alprazolam), barbiturates, or antiepileptic drugs, as abrupt withdrawal increases seizure risk with bupropion. 1, 5

Why This Seizure Occurred

The seizure risk with bupropion is dose-dependent, with approximately 0.1% incidence at 300 mg/day, but this can occur even at therapeutic doses in patients without predisposing factors. 1, 4 Your patient experienced this despite presumably being on standard dosing—this represents an idiosyncratic reaction that makes future use absolutely contraindicated. 1

Common pitfall: Seizures can occur even in patients with no personal or family history of seizure disorders, normal neurological examination, and at modest blood levels (as low as 83 ng/mL documented). 4, 5 The case literature shows seizures occurring 4 days to 6 months after starting bupropion. 5, 6

Alternative Treatment for ADHD and Depression

For Depression Management

Switch to an SSRI (sertraline, escitalopram, or fluoxetine) as first-line monotherapy. 7 These have equivalent efficacy to bupropion for major depressive disorder (42-49% remission rates) without seizure risk. 7

• Start sertraline 50 mg daily or escitalopram 10 mg daily, titrating based on response over 6-8 weeks. 7
• SSRIs have higher rates of sexual dysfunction compared to bupropion, but this is preferable to seizure risk. 7
• Monitor for suicidal ideation closely in the first 1-2 weeks, especially if patient is under 24 years old. 7, 1

For ADHD Management

Initiate stimulant medication (methylphenidate or amphetamine) as first-line treatment. 8 Bupropion is not FDA-approved for ADHD and should never be restarted after seizure. 1

• Methylphenidate starting dose: Begin with immediate-release 5 mg twice daily, titrating by 5-10 mg weekly based on response. 8
• Monitor for tic exacerbation (though controlled studies show MPH doesn't worsen tics in most patients). 8
• If seizure disorder develops: Stabilize on antiepileptic drugs first before considering stimulants, as high-dose methylphenidate can cause seizures in adults. 8

Alternative non-stimulant option: Atomoxetine 40 mg daily, titrating to 60-80 mg daily over 7-14 days (maximum 100 mg/day or 1.4 mg/kg/day). 8 This has no seizure risk and addresses both ADHD and depressive symptoms. 8

Monitoring and Follow-Up

• Neurology consultation required if this was a confirmed seizure to determine if antiepileptic drugs are needed. 9
• Repeat EEG in 2-4 weeks if initial EEG was abnormal, as bupropion-induced EEG changes typically resolve within this timeframe. 4
• Do not attempt medication withdrawal of any antiepileptic drugs started until seizure-free for at least 2 years. 9
• Counsel patient that bupropion in any formulation (immediate-release, SR, XL, or combination products like naltrexone-bupropion) is permanently contraindicated. 1

Critical Safety Warning

Never restart bupropion. Even if the patient had excellent response for depression or ADHD, the occurrence of seizure-like activity makes all bupropion-containing products absolutely contraindicated for life. 1 This includes ZYBAN (for smoking cessation), WELLBUTRIN (all formulations), APLENZIN, and naltrexone-bupropion combinations. 1

The prognosis is generally excellent—most patients remain seizure-free after bupropion discontinuation without requiring long-term antiepileptic drugs, as documented in follow-up studies showing patients seizure-free 5 years later. 4