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

Treatment Approach for Major Depressive Disorder (MDD)

For patients with Major Depressive Disorder, clinicians should select between either cognitive behavioral therapy or second-generation antidepressants after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient. 1

Diagnostic Criteria for MDD

MDD is defined by the presence of five or more of the following symptoms for at least 2 weeks, with at least one symptom being depressed mood or loss of interest/pleasure:

• Depressed mood
• Diminished interest or pleasure in activities
• Significant weight loss/gain or appetite changes
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or energy loss
• Feelings of worthlessness or inappropriate guilt
• Poor concentration or indecisiveness
• Recurrent thoughts of death or suicidal ideation 2

First-Line Treatment Options

1. Cognitive Behavioral Therapy (CBT)

• Moderate-quality evidence shows CBT is as effective as second-generation antidepressants (SGAs) for MDD 1
• CBT has fewer adverse effects than SGAs and lower relapse rates 1
• Should be strongly considered as an alternative treatment to SGAs where available 1

2. Second-Generation Antidepressants (SGAs)

• Include SSRIs, SNRIs, and other medications targeting neurotransmitters 1
• Approximately 60-70% of patients respond to treatment 3
• More than 60% experience at least one adverse effect 1
• Up to 70% do not achieve remission during initial treatment attempt 1

Recommended SGA Starting Doses:

• Sertraline (Zoloft): Start at 50 mg once daily; may increase to maximum of 200 mg/day 4
• Fluoxetine (Prozac): Start at 20 mg once daily in the morning; may increase after several weeks if needed 5
• Citalopram/Escitalopram: Start at 10 mg daily (especially in elderly) 3

Treatment Algorithm

1. Initial Assessment:

   • Screen using validated tools (PHQ-9, Beck Depression Inventory) 2
   • Consider laboratory tests to rule out medical causes or contraindications to treatment 2
   • Assess suicide risk (higher risk during first weeks of SGA treatment) 3

2. First-Step Treatment Selection:

   • Choose between CBT or SGA based on:
     • Patient preference
     • Accessibility of treatment
     • Cost considerations
     • Comorbid conditions
     • Previous treatment response

3. For SGA Treatment:

   • Start with low to moderate dose of selected SGA
   • Assess patient status within 1-2 weeks of starting therapy 3
   • Evaluate treatment efficacy at approximately 6 weeks and 12 weeks 3
   • Continue treatment for 4-9 months after satisfactory response for first episode 3

4. For CBT Treatment:

   • Engage in structured therapy sessions
   • Monitor response regularly
   • Continue treatment through completion of protocol

5. If Inadequate Response After 6-8 Weeks:

   • Consider switching to a different SGA
   • Add CBT if patient is on medication only
   • Consider augmentation with a second pharmacologic agent 3

Special Considerations

Adverse Effects of SGAs

• Common side effects: constipation, diarrhea, dizziness, headache, insomnia, nausea, somnolence 1
• Major concerns: sexual dysfunction and suicidality 1
• Bupropion is associated with lower rates of sexual adverse events than fluoxetine and sertraline 1
• Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, and sertraline 1

Elderly Patients

• SSRIs (sertraline, citalopram, escitalopram) are preferred due to favorable side effect profiles and lower risk of drug interactions 3
• Avoid tertiary tricyclic antidepressants due to anticholinergic effects and cardiovascular risks 3
• For elderly patients, consider starting with lower doses:
  • Sertraline: 25-50 mg daily (max 200 mg daily)
  • Citalopram: 10 mg daily (max 20 mg daily due to QT prolongation risk)
  • Escitalopram: 10 mg daily (max 20 mg daily) 3

Monitoring Requirements

• Regular assessment using standardized measures (e.g., PHQ-9)
• Close monitoring for suicidal ideation, especially in first weeks of treatment 3
• Evaluate for comorbid anxiety disorders that frequently coexist with depression 3
• Watch for drug interactions, particularly in elderly patients on multiple medications 3

Common Pitfalls to Avoid

1. Starting with too low a dose of SGAs (sub-optimal dosing may lead to inadequate response) 6
2. Discontinuing treatment too early (continue for at least 16-24 weeks after response) 2
3. Failing to monitor for suicidality, especially in the first weeks of treatment 3
4. Overlooking drug interactions, particularly in patients on multiple medications 3
5. Not considering switching strategies when initial treatment fails 1

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