Augmentation Strategies for Treatment-Resistant Depression

Defining Treatment-Resistant Depression

At least two prior adequate antidepressant trials have failed, with each trial at adequate dose for a minimum of 4 weeks duration, according to the Depression and Anxiety guidelines 1, 2, 3

Lithium is a well-studied augmentation agent with established efficacy, particularly important for bipolar depression, where mood stabilizers should be the foundation, as recommended by clinical guidelines 5
Monitor therapeutic blood levels for lithium augmentation, as suggested by clinical guidelines 4
Gabapentin is not recommended for treatment-resistant depression, as stated by clinical guidelines 6

Six essential confounders must be evaluated, including depressive severity at baseline, duration of current episode, prior treatment intolerance, prior augmentation or combination therapy attempts, prior psychotherapy trials, and psychiatric comorbidities, according to the Depression and Anxiety guidelines 7, 8
Psychiatric comorbidities, especially substance use and personality disorders, should be considered before augmentation, as recommended by clinical guidelines 5

Maintain augmentation therapy for a minimum of 2 months to allow adequate dose titration and assessment of response, as suggested by the Depression and Anxiety guidelines 7, 8
For more severely resistant patients, longer trials may be needed given increased relapse risk, according to the Depression and Anxiety guidelines 7, 8
For bipolar depression with mood stabilizers, maintain therapy for at least 2 years after the last episode, as recommended by clinical guidelines 5

Do not exclude patients from augmentation trials who have failed multiple prior medications, as long as they meet treatment-resistant depression criteria, as stated by clinical guidelines 5

Track depressive symptoms with standardized measurement tools throughout treatment to identify incomplete remission and guide modifications, according to the Depression and Anxiety guidelines 8
Key outcomes to monitor include depressive severity, general psychiatric status, functional impairment, quality of life, suicidality reduction, and medication adherence, as recommended by the Depression and Anxiety guidelines 7, 8