Treatment for Treatment-Resistant Depression

Definition and Diagnosis

Treatment-resistant depression (TRD) is generally defined as failure to respond to at least two adequate trials of antidepressants with different mechanisms of action in the current depressive episode, according to the American Psychiatric Association 1, 2
An adequate trial requires the minimal approved dosage administered for at least four weeks, as recommended by the National Institute of Mental Health 3
Discontinuation of treatment before completing four weeks due to side effects should not be considered a treatment failure for establishing TRD, as stated by the American Psychiatric Association 1

The American Psychiatric Association recommends verifying failure of at least two adequate antidepressant trials with different mechanisms of action before confirming TRD diagnosis 1
The National Institute of Mental Health suggests ensuring each trial was at minimum effective dosage for at least 4 weeks before considering treatment failure 3
For highly refractory cases, the Depression and Anxiety society considers esketamine/ketamine as a treatment option 2
Patients with TRD who have failed multiple medications should not be excluded from treatment trials, according to the Molecular Psychiatry guidelines 4
Previous failure of psychotherapy should not alter the pharmacological treatment approach, as recommended by the American Psychiatric Association 1
All depression specifiers (melancholic, atypical, anxious, psychotic, mixed) should be considered within TRD, except bipolar depression, as stated by the Molecular Psychiatry guidelines 5
Transcranial magnetic stimulation (TMS) can be considered for patients who have failed medication trials, according to the Molecular Psychiatry guidelines 3
Psychotherapy, particularly cognitive behavioral therapy, can be used in conjunction with pharmacotherapy, as recommended by the American Psychiatric Association 1