What is the recommended approach for treating major depressive disorder?

Treatment Approach for Major Depressive Disorder

For acute major depressive disorder, initiate treatment with a second-generation antidepressant (such as an SSRI or SNRI) selected based on adverse effect profile, cost, and patient preference, starting at standard doses (e.g., sertraline 50 mg daily, escitalopram 10 mg daily, fluoxetine 20 mg daily), with early assessment within 1-2 weeks and treatment modification if inadequate response by 6-8 weeks. 1

Initial Pharmacotherapy Selection

Second-generation antidepressants are the recommended first-line treatment because they demonstrate similar efficacy to each other while offering lower toxicity in overdose compared to first-generation antidepressants (tricyclics and MAOIs). 1

Medication Selection Criteria

• Choose among second-generation antidepressants based on three factors: adverse effect profiles, cost, and patient preferences—not efficacy, as no single agent demonstrates superior effectiveness. 1, 2

• Available options include SSRIs (sertraline, escitalopram, fluoxetine, paroxetine, citalopram, fluvoxamine), SNRIs (venlafaxine, duloxetine), and other second-generation agents (bupropion, mirtazapine, trazodone). 1

Starting Doses

• Sertraline: 50 mg once daily 3
• Escitalopram: 10 mg once daily 4
• Fluoxetine: 20 mg once daily 5
• Paroxetine: 20 mg once daily 5
• Citalopram: 20 mg once daily 5

Note that while higher starting doses may increase response rates (54.8% vs 50.8%), they also significantly increase discontinuation due to adverse events (16.5% vs 9.8%), making standard starting doses the safer initial approach. 5

Early Monitoring Protocol

Begin assessment of patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation. 1, 2

Critical Safety Monitoring

• Monitor closely for increased suicidal thoughts and behaviors during the first 1-2 months of treatment, as SSRIs carry an increased risk for suicide attempts compared to placebo. 2

• Assess for common adverse effects including sexual dysfunction, gastrointestinal symptoms, and activation/agitation. 2

• Continue regular monitoring throughout the acute treatment phase. 1

Treatment Response Timeline

Response is defined as a 50% reduction in depression severity using validated tools such as the Patient Health Questionnaire or Hamilton Depression Rating Scale. 2

Decision Point at 6-8 Weeks

• If the patient does not demonstrate adequate response within 6-8 weeks, modify treatment. 1, 2

• Modification options include dose escalation (up to maximum of 200 mg/day for sertraline), switching to a different antidepressant, or augmentation strategies. 3

• Do not change doses at intervals less than 1 week due to the 24-hour elimination half-life of most SSRIs (except fluoxetine, which has a longer half-life of 2-7 days). 3

Continuation and Maintenance Treatment

First Episode of Major Depression

Continue treatment for 4-9 months after achieving satisfactory response in patients with a first episode. 1, 2

Recurrent Depression

For patients with two or more previous episodes, extend maintenance treatment to at least 1 year or longer to prevent recurrence. 1, 2

• The distinction matters: relapse occurs during acute or continuation phases (same episode), while recurrence occurs during maintenance phase (new episode). 1, 2

• Chronic depression requires maintenance treatment extending beyond 9 months. 2

Combination with Psychotherapy

Consider combining pharmacotherapy with psychotherapy, particularly cognitive behavioral therapy, as this represents the most effective approach for chronic depression. 2, 6

• Psychotherapy options include cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapies. 2

• Combining medications, psychotherapy, and somatic therapies remains the most effective strategy for treatment-resistant depression. 6

Common Pitfalls to Avoid

• Do not discontinue treatment prematurely—many patients require several months beyond initial response to prevent relapse. 1, 2

• Do not switch medications before allowing adequate time (6-8 weeks) for response, as premature switching may miss eventual responders. 1

• Do not ignore sexual dysfunction complaints, as this is a common reason for non-adherence; consider switching to agents with lower rates of sexual adverse events if this occurs. 2

• Do not assume all second-generation antidepressants are interchangeable for individual patients—while class efficacy is similar, individual response varies. 7, 8