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

Treatment of Major Depressive Disorder (MDD)

Cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) are equally effective as first-line monotherapy for moderate to severe MDD, with CBT having fewer adverse effects and lower relapse rates. 1

Initial Treatment Options

For Mild MDD:

• First-line: Cognitive Behavioral Therapy (CBT) 2
  • Fewer adverse effects than pharmacotherapy
  • Lower relapse rates compared to medication
  • Particularly effective for addressing specific symptoms like insomnia

For Moderate to Severe MDD:

• First-line options (choose one):
  1. CBT monotherapy 1, 2
  2. Second-generation antidepressant (SGA) monotherapy 1, 2
  3. Combination of CBT + SGA (may provide additional benefits) 1, 2

Pharmacotherapy Details

Recommended SGAs:

• SSRIs (first choice):
  • Sertraline: Start 50 mg daily (25 mg for panic disorder); max 200 mg daily 3
  • Fluoxetine: Start 20 mg daily (10 mg for lower-weight individuals); max 80 mg daily 4
  • Citalopram: Start 10-20 mg daily; max 40 mg daily (20 mg in elderly due to QT prolongation risk) 1
  • Escitalopram: Start 10 mg daily; max 20 mg daily 1

Important Medication Considerations:

• Side effect profiles differ:
  • Bupropion: Lower rates of sexual dysfunction 1
  • Paroxetine: Higher rates of sexual dysfunction 1

  • 60% of patients experience at least one adverse effect with SGAs 1

  • Common side effects: constipation, diarrhea, dizziness, headache, insomnia, nausea, somnolence 1

Treatment Monitoring and Adjustment

Assessment Timeline:

1. Initial follow-up: 1-2 weeks after starting therapy 1
2. Efficacy evaluation: At approximately 6 weeks and 12 weeks 1
3. Use standardized measures: PHQ-9 or other validated depression scales 1

When Initial Treatment Is Inadequate (after 6-8 weeks):

• If started on SGA:
  • Switch to a different SGA OR
  • Add CBT OR
  • Augment with a second pharmacologic agent 1, 2
• If started on CBT:
  • Add an SGA OR
  • Switch to a different psychotherapy approach 2

Special Populations

Children and Adolescents:

• Psychotherapy alone is superior to combined treatment or medication alone for reducing serious adverse events (1.9% vs 3.7% and 5.6% respectively) 5
• For medication: Start with lower doses (fluoxetine 10 mg daily for lower-weight children) 4
• Monitor closely for suicidal ideation, especially in first weeks of treatment 1

Elderly Patients:

• Use lower starting doses and titrate slowly 4
• Preferred medications due to favorable side effect profiles:
  • Sertraline (25-50 mg daily initially)
  • Citalopram (10 mg daily, max 20 mg)
  • Escitalopram (10 mg daily) 1

Maintenance Treatment

• Duration: Continue treatment for 4-9 months after satisfactory response for first episode 1
• Long-term: For recurrent depression, longer maintenance may be needed 3, 4
• Relapse prevention: Up to 70% of patients do not achieve remission during initial treatment 1

Critical Pitfalls to Avoid

1. Inadequate dose or duration: Ensure adequate trial (6-8 weeks) before changing strategy
2. Overlooking suicidality: Monitor closely, especially in first weeks of treatment and in youth 1
3. Missing drug interactions: Particularly important in elderly patients on multiple medications 1
4. Ignoring comorbidities: Anxiety disorders frequently coexist with depression 1
5. Discontinuing treatment too early: Premature discontinuation increases relapse risk

Advanced Treatment Options

For treatment-resistant depression (failure of two or more adequate trials):

• Ketamine or esketamine for patients who have not responded to other treatments 6
• Electroconvulsive therapy for multiple prior treatment failures or when rapid improvement is needed 6
• Psychedelic treatments only in research settings 6

Remember that up to 60-70% of patients respond to initial treatment with SGAs, but many will require treatment adjustments or combinations to achieve full remission 1.