Provide optimized antidepressant monotherapy with multiple drugs before considering antidepressant polypharmacy

Many patients with chronic or recurring major depressive disorder have suboptimal responses to the wide range of antidepressant medications available. When confronted with these patients, clinicians may augment the original antidepressant with other medications, including adjunctive treatment with a second or third antidepressant. Although it is a widely-used practice among psychiatrists and primary care physicians in high-income countries, evidence for the benefits of this type of antidepressant polypharmacy is limited. Care should be taken to utilize this approach only after failure of optimized monotherapy with different classes of antidepressants.