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Treatment Options for Refractory Depression

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

  1. Bupropion 400 mg/d + SSRI
  2. Olanzapine + fluoxetine 25/50 mg/d
  3. Venlafaxine + mirtazapine 30-45 mg/d
  4. Add lithium, aim up to 1.0 mmol/L concentration. 
  5. Add aripiprazole 2-20 mg/d
  6. 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 μg/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, dizziness at a high dose. 


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