What to do about headaches that started after initiating Wellbutrin (bupropion) therapy?

Management of Bupropion-Induced Headaches at 10 Days

Start with standard analgesics immediately—use NSAIDs (ibuprofen, naproxen, or aspirin) as first-line treatment while continuing bupropion, as headaches are a common early side effect that often resolve with continued use. 1, 2

Initial Symptomatic Treatment

Use NSAIDs as the preferred first-line therapy for bupropion-induced headaches:

• Ibuprofen, naproxen sodium, or aspirin have the strongest evidence for headache treatment 1
• Begin treatment immediately upon headache onset for maximum efficacy 1
• Acetaminophen alone is ineffective and should not be used as monotherapy 1
• The combination of acetaminophen-aspirin-caffeine is also effective if NSAIDs are contraindicated 1

Critical medication overuse prevention:

• Limit acute headache medication use to no more than 2 days per week to prevent rebound headaches 1
• NSAIDs should be used fewer than 15 days per month 1
• Completely avoid medications containing barbiturates, caffeine, butalbital, or opioids, as these carry the highest risk of medication-overuse headache 1

Decision Point: Continue vs. Discontinue Bupropion

At 10 days, headache is a recognized common side effect of bupropion that typically improves with continued use:

• The FDA label lists headache as a common adverse effect, particularly during initial treatment 2
• Research confirms headache occurs with bupropion, especially during dose titration 3, 4
• Most early side effects (insomnia, headache, dry mouth, dizziness, nausea) are transient and improve over 2-4 weeks 3

Continue bupropion if:

• Headaches are mild to moderate in severity and responding to NSAIDs 1
• No concerning neurological symptoms are present (see red flags below) 2
• The patient is tolerating the medication otherwise and showing early signs of therapeutic benefit 2

Consider discontinuing bupropion immediately if:

• Severe, persistent headaches unresponsive to standard analgesics develop 2
• New neurological symptoms appear: diplopia, visual changes, anisocoria, neck stiffness, jaw clenching, or dystonic symptoms 4, 5, 6
• Headaches worsen progressively rather than stabilizing or improving 2
• Neuropsychiatric symptoms emerge: severe agitation, mood changes, suicidal ideation, unusual behavioral changes 2

Preventive Therapy Consideration

Initiate preventive therapy only if headaches persist beyond 4 weeks and meet specific criteria:

• Two or more headache attacks per month producing disability for 3+ days per month 1, 7
• Acute medications being used more than twice per week 1, 7

If preventive therapy becomes necessary, amitriptyline is the first-line choice:

• Start with 10-25 mg at bedtime, gradually titrate to 30-150 mg/day over weeks to months 7, 8
• Particularly beneficial when psychiatric comorbidity exists (depression, anxiety) 7
• Requires 2-3 months at therapeutic dose before declaring treatment failure 7, 8
• Common side effects include drowsiness, weight gain, dry mouth, and constipation 7, 8

Alternative first-line preventive options if amitriptyline is contraindicated:

• Propranolol 80-240 mg/day for pure migraine-type headaches 7, 8
• Topiramate for patients with obesity or chronic daily headaches 7

Critical Pitfalls to Avoid

Do not prematurely discontinue bupropion for mild headaches:

• Many patients experience transient headaches during the first 2-4 weeks that resolve spontaneously 3
• Premature discontinuation denies patients the therapeutic benefits of bupropion for depression or smoking cessation 3

Do not use opioids or butalbital-containing compounds for routine headache management:

• These medications carry the highest risk of medication-overuse headache and should be completely avoided 1
• Reserve rescue medications only for severe, refractory cases under close monitoring 1

Monitor for serious neuropsychiatric adverse events:

• The FDA requires monitoring for agitation, depressed mood, behavioral changes, and suicidal ideation, especially during initial treatment and dose changes 2
• Families and caregivers should be educated to report these symptoms immediately 2

Watch for seizure risk factors:

• Bupropion lowers seizure threshold in a dose-dependent manner 2
• Risk increases with concomitant medications (antipsychotics, tricyclic antidepressants, theophylline, systemic corticosteroids) 2
• Never exceed 450 mg/day total dose and ensure gradual titration 2