What are the differential diagnoses for this patient's headaches and migraines, and could any of her current medications, including bupropion (Bupropion HCl ER), duloxetine (Duloxetine HCl), and aripiprazole (Aripiprazole), be contributing to her symptoms?

Differential Diagnoses and Medication-Induced Headache Assessment

Primary Differential Diagnoses

This patient's presentation is most consistent with chronic migraine rather than sinusitis, given the CT findings showing improvement in sphenoid sinus thickening and the characteristic migraine features. 1

Most Likely Diagnosis: Chronic Migraine

• Patient meets criteria for chronic migraine: ≥15 headache days per month for >3 months, with migraine features on ≥8 days per month 1
• Unilateral location (left-sided), severe intensity requiring bed rest, and temporal/occipital spread are classic migraine characteristics 1
• Previous response to Maxalt (triptan) strongly supports migraine diagnosis 1
• Sinusitis is the most frequent misdiagnosis given to migraine patients, with delays in proper diagnosis averaging 7.75 years 2

Secondary Consideration: Medication Overuse Headache (MOH)

• Patient takes multiple medications that could contribute to MOH: clonazepam PRN, armodafinil BID, omeprazole, and famotidine 1
• MOH develops from regular overuse for >3 months of acute medications on ≥10 days/month 1
• MOH is reported only in patients misdiagnosed as sinusitis and is an important differential for chronic migraine 2, 1

Less Likely: Residual Sphenoid Sinusitis

• CT shows less thickening than two months ago, making active sinusitis unlikely 1
• Lack of purulent rhinorrhea, fever, or response to antibiotics argues against bacterial sinusitis 1
• Headache attributed to chronic sinusitis could actually be a migraine equivalent 1

Other Differentials to Consider

• Tension-type headache: Less likely given unilateral location, severe intensity, and associated symptoms 1
• Cluster headache: Excluded by longer attack duration (days vs. 15-180 minutes) and lack of autonomic symptoms 1

Medications Contributing to Headaches

High-Risk Medications Currently Used

Armodafinil (250 mg BID):

• Stimulant medication that commonly causes headaches as an adverse effect 3
• Twice-daily dosing at maximum dose (250 mg) significantly increases headache risk
• This is the most likely medication culprit given the high dose and frequency

Bupropion XL (300 mg + 150 mg AM):

• Total daily dose of 450 mg exceeds standard maximum dosing
• Headache is a common adverse effect of bupropion 3
• Stimulant properties may exacerbate migraine frequency

Duloxetine (60 mg BID):

• Total daily dose of 120 mg
• While duloxetine has evidence for migraine prevention at 60-120 mg daily, headache is listed as a common adverse effect (12% incidence in pediatric trials) 3, 4, 5
• SNRIs including duloxetine have evidence for migraine prevention but can paradoxically cause headaches during initiation or dose changes 5

Aripiprazole (2 mg daily):

• Headache reported in 27% of adult patients vs. 23% placebo in clinical trials 3
• Dizziness (10% vs. 7% placebo) and akathisia (10% vs. 4% placebo) are common and may worsen migraine-related disability 3

Vyvanse (50 mg daily):

• Amphetamine-based stimulant with headache as common adverse effect
• Combined with armodafinil creates significant stimulant burden

Medication Overuse Pattern

• Patient uses clonazepam PRN for headaches, which can lead to rebound headaches with frequent use 1, 6
• Chronic use of multiple symptomatic medications (benzodiazepines, stimulants) increases risk of medication overuse headache 6

Critical Management Recommendations

Immediate Actions

• Restart Maxalt for acute migraine attacks as previously effective 1
• Limit acute medication use to <10 days per month to prevent MOH 1, 7
• Avoid opioids or butalbital-containing medications 7

Medication Adjustments to Consider

• Reduce or discontinue armodafinil - highest likelihood of contributing to headaches given dose and frequency
• Consolidate bupropion to single daily dose of 300 mg XL rather than split dosing
• Evaluate necessity of twice-daily duloxetine; consider reducing to 60 mg daily if depression is controlled 4, 5
• Monitor clonazepam use frequency; if used >2 days/week for headaches, this constitutes medication overuse 7

Prophylactic Treatment

• Duloxetine at 60-120 mg daily has evidence for migraine prevention in non-depressed individuals (52% had ≥50% reduction in headache days) 4, 5
• Current duloxetine may provide prophylaxis if stimulant medications are reduced
• Consider topiramate if duloxetine ineffective, as it has the strongest evidence for chronic migraine prevention 1

Critical Pitfalls to Avoid

• Do not attribute all symptoms to sinusitis when CT shows improvement - this delays proper migraine treatment by years 2
• Do not overlook medication overuse headache - present in 73% of chronic migraine patients in tertiary centers 1, 6
• Do not continue ineffective treatments - patient had no relief from sinus surgery or antibiotics, confirming non-sinus etiology 2
• Do not use NSAIDs given kidney function concerns - patient correctly avoiding ibuprofen 1
• Do not add more acute medications without addressing overuse pattern - this worsens chronification 6, 8