Treatment of Major Depressive Disorder, Single Episode, Mild
For mild major depressive disorder, cognitive behavioral therapy (CBT) alone is the recommended first-line treatment, with antidepressants reserved for patients who do not respond to psychotherapy or prefer medication. 1
Evidence-Based Treatment Approach
First-Line Treatment Selection
Cognitive behavioral therapy should be initiated as monotherapy for mild depression, as it has equivalent effectiveness to second-generation antidepressants with moderate-quality evidence supporting this approach 2, 1
Antidepressants should not be used for initial treatment of mild depression, as drug-placebo differences are virtually nonexistent in mild depression, with clinically important differences only emerging in moderate to severe depression 2
The American College of Physicians explicitly recommends against antidepressants for initial treatment of adults with depressive symptoms in the absence of current or prior moderate or severe depressive episodes 2
When Pharmacotherapy Is Considered
If CBT is unavailable, declined by the patient, or ineffective after an adequate trial (typically 6-8 weeks), second-generation antidepressants may be considered:
Select SSRIs or SNRIs based on adverse effect profiles, cost, and patient preferences rather than efficacy, as no second-generation antidepressant has demonstrated superior effectiveness over another 2
Sertraline 50 mg once daily is a reasonable starting dose if pharmacotherapy is chosen, as it is FDA-approved for major depressive disorder with this initial dosing 3
Fluoxetine is another appropriate option with well-established efficacy in major depressive disorder 4
Critical Monitoring Parameters
Begin monitoring within 1-2 weeks of treatment initiation (whether psychotherapy or medication) to assess therapeutic response, adverse effects, and emergence of suicidal ideation 2
SSRIs carry an increased risk for suicide attempts compared to placebo, making early and frequent monitoring essential 2
Modify treatment if inadequate response occurs by 6-8 weeks, including dose adjustment, switching agents, or adding augmentation strategies 2, 1
Treatment Duration
Continue treatment for 4-9 months after satisfactory response for first episodes of major depressive disorder to prevent relapse 2, 1
For patients with two or more prior episodes, longer duration therapy (≥1 year) may be beneficial 2
Common Pitfalls to Avoid
Do not prescribe antidepressants reflexively for mild depression without first considering psychotherapy, as evidence shows minimal benefit over placebo in this population 2
Avoid inadequate dosing or premature discontinuation before therapeutic effects are achieved (typically 4-6 weeks for medications) 1
Do not fail to assess and document treatment adherence, as up to 50% of patients with MDD demonstrate non-adherence 1
Avoid stopping treatment prematurely after symptom resolution—continue for minimum 4-9 months to prevent relapse 2