Treatment Options for Treatment-Resistant Depression

Definition and Diagnosis

The American College of Cardiology is not applicable here, however, treatment-resistant depression (TRD) is defined as failure to respond to at least two adequate trials of antidepressants with different mechanisms of action in the current depressive episode 1
An adequate trial requires the minimal approved dosage administered for at least four weeks 1
Discontinuation due to side effects before completing four weeks should not be considered a treatment failure for establishing TRD 1
For long current episodes, only treatment failures within the last two years should be considered when defining TRD 2

Aripiprazole augmentation can be considered after inadequate response to at least one antidepressant treatment at adequate dose for at least 4 weeks 3
The Depression and Anxiety society considers esketamine/ketamine a treatment option for highly refractory cases 1

Transcranial magnetic stimulation (TMS) can be considered for patients who have failed medication trials 1

Verify TRD diagnosis: Confirm failure of at least two adequate antidepressant trials with different mechanisms of action 1
First-line approach: Augmentation with atypical antipsychotics (aripiprazole) 3

Ensure adequate dosing and duration (minimum effective dosage for at least 4 weeks) before declaring treatment failure 1