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The review evaluated the following classes of interventions: depression-focused psychotherapy, CAM, exercise, and SGAs.Outcomes assessed included benefits in response (often defined as ≥50% improvement in HAM-D scores), remission (often defined as a HAM-D score ≤7), speed of response, speed of remission, relapse, quality of life, functional capacity (as assessed by various scales), reduction of suicidality, or reduction of hospitalization.Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture, ω-3 fatty acids, ]), exercise, and second-generation antidepressants.Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms.In contrast, subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses.The treatment of depression can be characterized by 3 phases (Figure 1): acute (6 to 12 weeks), continuation (4 to 9 months), and maintenance (≥1 year) (7).

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Response to treatment (typically defined as ≥50% reduction in measured severity) can be quantified using various tools, such as the Patient Health Questionnaire-9 (PHQ-9) (7) or the Hamilton Depression Rating Scale (HAM-D) (8).The CAM treatments include acupuncture, meditation, ω-3 fatty acids, -methionine (SAMe), St. Exercise includes a broad range of activities that can be done for varying durations, in classes, individually, or in informal groups.For pharmacologic therapy, the scope of this guideline is limited to second-generation antidepressants (SGAs) (selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and selective serotonin norepinephrine reuptake inhibitors).First-generation antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy.The purpose of this guideline from the American College of Physicians (ACP) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs (including serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, bupropion, mirtazapine, nefazodone, and trazodone), alone or in combination, for MDD.The estimated economic burden associated with depression was .1 billion in 2000 and is probably higher today (2).

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