What are the treatment guidelines for Major Depressive Disorder (MDD)?

Treatment Guidelines for Major Depressive Disorder (MDD)

Both cognitive behavioral therapy (CBT) and second-generation antidepressants (SGAs) are equally effective as first-line treatments for major depressive disorder and should be selected based on patient factors and preferences. 1, 2

Diagnostic Criteria

• MDD is defined as depressed mood or loss of pleasure/interest along with other symptoms that last for at least 2 weeks and affect normal functioning 1, 2
• Diagnosis requires at least 5 symptoms during a 2-week period, including depressed mood, anhedonia, sleep disturbances, psychomotor changes, fatigue, feelings of worthlessness, concentration difficulties, or suicidal thoughts 1, 2
• Assessment tools include the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Rating Scale (HAM-D) to measure severity and monitor treatment response 1, 2

Treatment Phases

• Acute phase (6-12 weeks): Focus on symptom reduction 1, 2
• Continuation phase (4-9 months): Prevent relapse 1, 2
• Maintenance phase (≥1 year): Prevent recurrence, especially important for patients with multiple episodes 1, 2

First-Line Treatment Options

Pharmacotherapy (SGAs)

• Start with an SSRI (sertraline, escitalopram, fluoxetine, paroxetine, citalopram) or SNRI 1
• Initial dosing:
  • Sertraline: Start at 50 mg once daily, may increase to maximum 200 mg/day 3
  • Escitalopram: 10 mg daily initially 4
  • Bupropion: Start at 150 mg once daily, may increase to 300 mg after 4 days 5
• Dose adjustments should not occur at intervals less than 1 week due to the elimination half-lives of these medications 3, 5
• Higher doses of SSRIs appear slightly more effective but with decreased tolerability 6
• Continue treatment for at least 4-9 months after satisfactory response for first episodes 3, 2

Psychotherapy

• Cognitive Behavioral Therapy (CBT) has moderate-quality evidence supporting its effectiveness as equivalent to SGAs 1
• Other effective options include interpersonal therapy and psychodynamic therapies 1
• Moderate-quality evidence from 5 trials showed no difference in response rates between SGAs and CBT 1

Combination Therapy

• Low-quality evidence shows no significant difference in response or remission rates between SGA monotherapy and combination therapy with SGA plus CBT 1
• One trial showed improved work functioning with combination therapy compared to SGA monotherapy 1

Complementary and Alternative Medicine (CAM)

• St. John's Wort: Low-quality evidence from 9 trials showed no difference in response or remission compared to SGAs 1
• Acupuncture: Low-quality evidence shows combination therapy of SGAs with acupuncture improved treatment response compared to SGA monotherapy 1
• Omega-3 fatty acids: Low-quality evidence suggests SGAs are more effective 1

Treatment Algorithm

1. Initial Assessment: Determine severity using validated tools (PHQ-9, HAM-D) 1, 2
2. First-line Treatment: Choose between:
   • SGA (SSRI preferred) - Start at recommended initial dose 3, 5, 4
   • CBT - Weekly sessions for 12-16 weeks 1
   • Decision factors: Patient preference, previous treatment response, side effect profile, comorbidities 2
3. Monitor Response: Assess at 2-4 week intervals initially 2
4. Inadequate Response:
   • For SGA: Optimize dose before switching (wait 4-6 weeks at therapeutic dose) 3, 6
   • Consider switching to another SGA or adding psychotherapy 1
5. Maintenance: Continue treatment for at least 4-9 months after remission 1, 2

Common Pitfalls to Avoid

• Inadequate dosing or premature discontinuation before therapeutic effects are achieved (typically 4-6 weeks) 2, 6
• Failure to monitor for suicidality, especially during initial treatment period 5, 4
• Not continuing treatment long enough to prevent relapse (minimum 4-9 months after response) 2, 3
• Discontinuing medication abruptly rather than tapering, which can lead to discontinuation symptoms 3, 4
• Overlooking potential drug interactions, especially when switching between antidepressants 4, 7

Special Considerations

• SGAs have lower toxicity in overdose compared to first-generation antidepressants (tricyclics, MAOIs) 1, 7
• Response to treatment is typically defined as ≥50% reduction in measured severity using validated tools 1, 2
• Treatment-resistant depression (failure to respond to two or more adequate antidepressant trials) requires specialized approaches 2, 8
• Antidepressants carry boxed warnings about increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults 5