Combination Therapy for Treatment-Resistant Depression

Rationale and Efficacy

Dual-acting antidepressants, such as those affecting both norepinephrine and serotonin, have demonstrated superiority over SSRIs in severe depression, with tertiary amine tricyclics showing particular advantage in hospitalized or severely depressed patients, according to the American Psychiatric Association 1
SNRIs like venlafaxine provide marginally superior remission rates compared to SSRIs (49% vs. 42%) in major depressive disorder, with additional benefits for patients with comorbid pain disorders, as recommended by the American Academy of Family Physicians 2

The combination of mirtazapine and venlafaxine should only be used after failure of first-line treatments, as second-generation antidepressants (SSRIs and SNRIs) are considered equally effective for treatment-naïve patients, according to the American College of Physicians 3