What is the first-line treatment approach for major depression?

Mild depression: psychotherapy (CBT, IPT) or pharmacotherapy. Moderate-severe: combination of both preferred. SSRIs (sertraline, escitalopram) or SNRIs (venlafaxine, duloxetine) as first-line medications. Allow 4-6 weeks for response. If inadequate response, optimize dose, switch class, or augment. Continue treatment 6-12 months after remission for first episode, longer for recurrent depression. Screen for bipolar before starting antidepressants.