Adjunctive Treatment for Major Depressive Disorder

Guideline-Based Recommendations

The American College of Physicians recommends psychological interventions, such as cognitive behavioral therapy, interpersonal therapy, and acceptance and commitment therapy, as adjunctive therapies for major depressive disorder 1
The American College of Physicians also recommends complementary approaches with evidence, including omega-3 fatty acids, S-adenosyl-l-methionine (SAMe), St. John's wort, exercise, acupuncture, meditation, and yoga, as adjunctive therapies for major depressive disorder 1
The World Health Organization recommends problem-solving treatment as the primary adjunctive therapy for moderate to severe depression when added to ongoing pharmacotherapy, prioritizing non-pharmacologic augmentation 2

The World Health Organization recommends cognitive behavioral therapy and interpersonal therapy as alternative evidence-based psychological options for adjunctive treatment of major depressive disorder 2
The American College of Physicians recommends second-generation antidepressants as pharmacologic options for adjunctive treatment of major depressive disorder 1
Bupropion SR is recommended for pharmacologic augmentation, with lower discontinuation rates due to adverse events compared to other options 2
Aripiprazole is recommended for pharmacologic augmentation, with FDA-approval for adjunctive treatment in unipolar depression 2

Omega-3 fatty acids (EPA and DHA) are recommended for patients with coronary heart disease and depression, with a minimum of 30 minutes of moderate-intensity physical activity on most days 3
Exercise is recommended as a complementary approach, with a minimum of 30 minutes of moderate-intensity physical activity on most days 3

The first step in the clinical decision algorithm is to add evidence-based psychological intervention (problem-solving therapy or CBT) to ongoing antidepressant, with assessment at 4 and 8 weeks using validated instruments 2
If there is insufficient response after 8 weeks, pharmacologic augmentation (bupropion SR or aripiprazole) should be added, with monitoring for adverse events and treatment adherence throughout 2

Cognitive behavioral therapy (CBT) provides similar efficacy and should be offered as an alternative evidence-based option, according to the Annals of Internal Medicine 4

Both aripiprazole and bupropion SR provide similar symptomatic relief when used as augmentation strategies, as reported by the Annals of Internal Medicine 4, 5
Different switching and augmentation strategies provide similar symptom relief, so selection should be based on adverse event profiles and patient-specific factors, as noted by the Annals of Internal Medicine 4, 5

S-adenosyl-L-methionine (SAMe) has demonstrated efficacy as an adjunctive treatment, according to the Annals of Internal Medicine 4
St. John's wort shows evidence for efficacy but requires caution regarding drug interactions, as reported by the Annals of Internal Medicine 4
Acupuncture, meditation, and yoga represent additional evidence-based complementary options, as noted by the Annals of Internal Medicine 4

The certainty of evidence for most treatment comparisons is low, with high dropout rates, dosing inequalities, and small sample sizes limiting confidence, as reported by the Annals of Internal Medicine 4, 5