What to do for a patient on Wellbutrin (bupropion) 300XL and Prozac (fluoxetine) 50mg experiencing worsening tinnitus after a recent increase in Wellbutrin dose?

Management of Worsening Tinnitus After Bupropion Dose Increase

Reduce bupropion back to the previous dose (or discontinue it entirely) immediately, as this medication is a known cause of drug-induced tinnitus and the temporal relationship between dose escalation and symptom worsening strongly implicates it as the culprit. 1

Immediate Action Required

• Decrease bupropion from 300mg XL to the prior dose (or discontinue if tinnitus is severe), as bupropion-related tinnitus typically resolves after dose reduction or discontinuation 2, 1
• The temporal relationship between dose increase and symptom worsening is the strongest evidence that bupropion is causative 1
• Tinnitus from SSRIs like fluoxetine can occur but is rare and typically develops within weeks of initiation, not after stable dosing 3
• Since fluoxetine 50mg was stable before the bupropion increase, it is unlikely to be the primary cause 3

Diagnostic Evaluation While Adjusting Medication

Obtain comprehensive audiologic examination urgently to document any hearing changes and rule out sudden sensorineural hearing loss, as the American Academy of Otolaryngology-Head and Neck Surgery recommends prompt audiometry for unilateral or persistent tinnitus 4

• Perform targeted otoscopic examination to exclude retrotympanic masses or vascular abnormalities 5, 6
• Determine if tinnitus is pulsatile versus non-pulsatile, as pulsatile tinnitus requires immediate vascular imaging workup 5, 6
• If tinnitus is unilateral, pulsatile, or associated with asymmetric hearing loss on audiometry, obtain imaging (CT temporal bone or CTA head/neck depending on suspected etiology) 5, 6, 4
• For bilateral non-pulsatile tinnitus without focal findings, imaging is not indicated 4

Medication Management Strategy

Do not add antidepressants, anticonvulsants, or anxiolytics specifically to treat tinnitus, as the American Academy of Otolaryngology-Head and Neck Surgery recommends against these medications for routine tinnitus treatment 4

• If depression requires continued antidepressant therapy after bupropion reduction/discontinuation, consider switching to an alternative antidepressant with lower tinnitus risk 7, 4
• Duloxetine shows the strongest association with tinnitus among antidepressants (ROR 11.99) and should be avoided 1
• SSRIs have mixed evidence: sertraline can rarely cause tinnitus even at low doses 3, but fluoxetine at stable doses is less likely to be causative 8
• Avoid dietary supplements (Ginkgo biloba, melatonin, zinc) as they lack evidence for tinnitus treatment 4

Expected Timeline and Follow-Up

• Tinnitus from medication typically improves within days to weeks after dose reduction or discontinuation 3
• If tinnitus persists beyond 2-4 weeks after bupropion adjustment, reassess for alternative etiologies including fluoxetine contribution or underlying structural causes 6, 4
• Schedule audiologic follow-up at 4 weeks to document improvement or persistence 4

Long-Term Management if Tinnitus Persists

Recommend cognitive behavioral therapy (CBT) if tinnitus remains bothersome after 6 months, as this has the strongest evidence for improving quality of life in persistent tinnitus 4

• Consider hearing aid evaluation even if hearing loss is mild, as amplification can reduce tinnitus perception 4
• Sound therapy may be offered as an option for persistent bothersome tinnitus 4
• Educate patient that most medication-induced tinnitus resolves after drug discontinuation, but some cases may persist 1, 3

Critical Pitfalls to Avoid

• Do not continue escalating bupropion dose hoping tinnitus will resolve with time—it typically worsens with higher doses 2, 1
• Do not dismiss worsening tinnitus as coincidental when it temporally correlates with medication changes 1
• Do not add multiple medications to treat tinnitus symptoms, as polypharmacy increases risk without proven benefit 4
• Do not delay audiologic evaluation, as missing sudden sensorineural hearing loss significantly worsens prognosis 9