Treatment of Refractory Depression When depression does not improve with three sequential trials of antidepressants, we call it treatment-refractory depression. the following is the list of choices for treatment-refractory depression. First-line Treatment Options Bupropion 400 mg/d + SSRI Olanzapine + fluoxetine 25/50 mg/d Venlafaxine + mirtazapine 30-45 mg/d Add lithium, aim up to 1.0 mmol/L concentration. Add aripiprazole 2-20 mg/d Add quetiapine 150-300 mg/d Second-line Choices Ketamine-IV (0.5 mg/kg IV over 40 minutes), à rapidly effective, by the anesthetist High-dose venlafaxine à 200 mg/d, à NICE recommended, monitor BP Electroconvulsive therapy à effective, stigmatized Add risperidone 0.5-3 mg/d, à weak evidence, hypotension Add Triiodothyronine 20–50 μ g/d, à reasonable evidence, monitor TFTs Lamotrigine, 100, 200, 400 mg/d, à best tolerated, risk of rash SSRI+ buspirone 60 mg/d, à research-supported, dizzi