The acute phase of treatment lasts a minimum of 6–12 weeks. During this phase, the aims of treatment are to induce remission of symptoms and achieve a full return to the patient's baseline level of functioning. In addition to general psychiatric management (described in Section II.A), treatment may consist of pharmacotherapy or other somatic therapies (e.g., ECT, light therapy), depression-focused psychotherapy, or the combination of somatic and psychosocial therapies. Selection of an initial treatment modality is influenced by several factors, including the symptom profile, the presence of co-occurring disorders or psychosocial stressors, the patient's prior treatment experience, and the patient's preference.

Psychiatrists should present patients with information concerning the evidence for a broad range of treatment options, including somatic therapies and psychosocial interventions. Antidepressant medications can be used as an initial treatment modality by patients with mild, moderate, or severe major depressive disorder. Clinical features that may suggest that medications are the preferred treatment modality include a history of prior positive response to antidepressant medications, the presence of moderate to severe symptoms, significant sleep or appetite disturbances, agitation, patient preference, and anticipation of the need for maintenance therapy. Patients with major depressive disorder with psychotic features require either the combined use of antidepressant and antipsychotic medications or ECT.

Psychotherapy may also be considered as monotherapy for patients with mild to moderate major depressive disorder. The availability of clinicians with appropriate training and expertise in specific psychotherapeutic approaches can be a factor in choosing a psychotherapy (67). Other factors that can influence this choice may be the psychosocial context, patient preference, prior positive response to psychotherapy, the presence of significant psychosocial stressors or interpersonal difficulties, co-occurring Axis II disorders, or the stage, chronicity, and severity of the major depressive episode. Specifically, many severely depressed patients will require both a depression-focused psychotherapy and a somatic treatment such as pharmacotherapy. Pregnancy, lactation, or the wish to become pregnant may tilt a decision toward psychotherapy as an initial treatment (see Section III.B.6). Given the lower occurrence of side effects and suggestion of enduring benefits associated with depression-focused psychotherapies (68), such treatments might be preferable alternatives to pharmacotherapy for some patients with mild to moderate depression.

Combining a depression-focused psychotherapy and pharmacotherapy may be a useful initial treatment choice for patients with moderate to severe major depressive disorder. Other indications for combined treatment include chronic forms of depression, psychosocial issues, intrapsychic conflict, interpersonal problems, or a co-occurring Axis II disorder. In addition, patients who have had a history of only partial response to adequate trials of single treatment modalities may benefit from combined treatment. Poor adherence with pharmacotherapy may also warrant combined treatment with medications and psychotherapy focused on treatment adherence.

Electroconvulsive therapy should be considered as a potential treatment option for all patients with major depressive disorder who have psychotic features or catatonia and for those with an urgent need for response, such as patients who are suicidal or who are nutritionally compromised as a result of refusing food. Electroconvulsive therapy may also be the treatment modality of choice for patients with major depressive disorder who have a high degree of symptom severity. Other considerations include the presence of co-occurring general medical conditions that preclude the use of antidepressant medications, a prior history of positive response to ECT, and patient preference. Evidence for TMS is currently insufficient to support its use in the initial treatment of major depressive disorder.

If a patient with mild depression wishes to try exercise alone for several weeks as a first intervention, there is little to argue against it (Section II.A.10), provided the patient is sufficiently monitored for an abrupt worsening of mood or adverse physical effects (e.g., ischemia or musculoskeletal symptoms). The dose of exercise and adherence to an exercise regimen may be particularly important to monitor in the assessment of whether an exercise intervention is useful for major depressive disorder (69, 70). If mood fails to improve after a few weeks with exercise alone, the psychiatrist should recommend medication or psychotherapy. For patients with depression of any severity and no medical contraindication to exercise, physical activity is a reasonable addition to a treatment plan for major depressive disorder. The optimal regimen is one the patient prefers and will adhere to.

Figure 1 summarizes treatment modalities that may be appropriate during the acute phase of treatment depending on the severity of the patient's symptoms and other associated features of the depressive episode. It is important to note that other factors may be relevant to treatment decisions for individual patients and that determinations of episode severity are imprecise, although rating scales may be helpful in assessing the magnitude of depressive symptoms and their effects on functional status and quality of life (see Sections II.A.7 and II.A.8).