Combination Therapy with Duloxetine and Bupropion

Dosing and Administration

The standard therapeutic dose of duloxetine for depression and pain conditions is 60mg, according to the Praxis Medical Insights guideline society 1, 2
Bupropion should be initiated at 37.5mg every morning and increased by 37.5mg every 3 days, with a maximum of 150mg twice daily, as recommended by the American family physician guideline society 3
Bupropion should be given before 3 p.m. as the second dose to minimize insomnia risk, as suggested by the American family physician guideline society 3

Duloxetine can cause modest hypertension and increases in systolic and diastolic blood pressure, and blood pressure should be monitored at each follow-up visit, according to the Praxis Medical Insights guideline society 1
Bupropion should not be used in patients with seizure disorders, as it lowers the seizure threshold, and the maximum recommended dose is 450mg per day to minimize seizure risk, as recommended by the American family physician and American Journal of Obstetrics and Gynecology guideline societies 3, 5
Duloxetine is not recommended for patients with creatinine clearance <30 mL/min, according to the Praxis Medical Insights guideline society 1

Duloxetine inhibits CYP2D6, which could theoretically affect metabolism of other medications, as noted by the Praxis Medical Insights guideline society 4
Both medications are extensively metabolized in the liver, requiring caution with other hepatically cleared drugs, although no specific guideline society is cited for this fact, it is associated with 4

If either medication needs to be stopped, duloxetine should be tapered gradually over at least 2-4 weeks to minimize withdrawal symptoms, as recommended by the Praxis Medical Insights guideline society 1
Bupropion can also be tapered over 10-14 days to limit withdrawal symptoms, according to the American family physician guideline society 3
If the combination proves ineffective after 4-8 weeks at therapeutic doses, alternative considerations include switching to pregabalin or gabapentin for neuropathic pain components, as suggested by the Praxis Medical Insights guideline society 4