What is the recommended treatment for Major Depressive Disorder (MDD)?

Treatment of Major Depressive Disorder (MDD)

The recommended first-line treatment for Major Depressive Disorder (MDD) is either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs), with the choice between them based on discussing treatment effects, adverse effect profiles, cost, accessibility, and patient preferences. 1

Treatment Options and Efficacy

Psychotherapy vs. Pharmacotherapy

• Moderate-quality evidence shows no difference in response rates between SGAs (fluoxetine, fluvoxamine, paroxetine, or sertraline) and CBT after 8 to 52 weeks of treatment 2
• Low-quality evidence shows no difference in remission rates between SGAs and CBT 2
• CBT has fewer adverse effects than SGAs and lower relapse rates 1
• Other psychotherapy options with similar efficacy to SGAs include:
  • Interpersonal therapy (low-quality evidence) 2
  • Psychodynamic therapy (low-quality evidence) 2

Pharmacotherapy Options

• Second-generation antidepressants (SGAs) are commonly used with 60-70% of patients responding to treatment 1
• Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed SGAs
• Bupropion is FDA-approved for MDD and has a lower rate of sexual adverse events compared to fluoxetine and sertraline 1, 3
• Higher doses of SSRIs appear slightly more effective in MDD, with benefits plateauing at around 50 mg of fluoxetine equivalents 4

Treatment Algorithm

Step 1: Initial Treatment Selection

1. Assess depression severity using standardized measures (e.g., PHQ-9)
2. Choose between CBT or SGA based on:
   • Patient preference
   • Accessibility of treatment
   • Cost considerations
   • Medical comorbidities
   • Previous treatment response
   • Side effect concerns

Step 2: If Selecting Pharmacotherapy

• Starting dose recommendations:
  • Start with a low to moderate dose of an SGA 1
  • For bupropion XL: 150 mg once daily in the morning for 4 days, then increase to target dose of 300 mg once daily 3
  • For SSRIs: Standard starting doses (e.g., 20 mg fluoxetine, 50 mg sertraline) 1
• Monitoring:
  • Assess patient status within 1-2 weeks of starting therapy 1
  • Monitor closely for worsening symptoms and emergence of suicidal thoughts, especially in the first weeks 1, 3
  • Regular assessment using standardized measures at approximately 6 weeks and 12 weeks 1

Step 3: Inadequate Response Management

• If inadequate response after 6-8 weeks, consider:
  • Switching to a different SGA
  • Adding CBT if on medication only
  • Augmenting with a second pharmacologic agent 1

Step 4: Continuation and Maintenance

• Continue treatment for 4-9 months after satisfactory response for a first episode 1
• For bupropion, periodically reassess the need for maintenance treatment 3

Important Considerations and Pitfalls

Side Effects

• More than 60% of patients experience at least one adverse effect when taking SGAs 1
• Common SGA side effects: constipation, diarrhea, dizziness, headache, insomnia, nausea, and somnolence 1
• Major concerns with SGAs include sexual dysfunction and suicidality 1
• Bupropion has a lower rate of sexual adverse effects compared to many SSRIs 1, 3

Suicidality Risk

• SGAs are associated with an increased risk for nonfatal suicide attempts, particularly in the initial weeks of treatment 1, 3
• Close monitoring is essential during the first weeks of treatment 1, 3

Special Populations

• For elderly patients, medications with favorable side effect profiles include:
  • Sertraline (25-50 mg initial, 200 mg maximum)
  • Citalopram (10 mg initial, 20 mg maximum due to QT prolongation risk)
  • Escitalopram (10 mg initial, 20 mg maximum) 1

Treatment Resistance

• Up to 70% of patients do not achieve remission during initial treatment 1
• Consider combination therapy (SGA plus CBT) for moderate to severe MDD 1
• Evaluate and treat possible comorbid anxiety disorders that frequently coexist with depression 1

By following this evidence-based approach to MDD treatment, clinicians can optimize outcomes while minimizing adverse effects, ultimately improving mortality, morbidity, and quality of life for patients with MDD.