What are the recommended treatment options for major depressive disorder in a psychiatry board interview?

Treatment Options for Major Depressive Disorder

First-Line Treatment Recommendation

For initial treatment of major depressive disorder, clinicians should offer either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs), as both demonstrate equivalent efficacy with moderate-quality evidence. 1, 2

Treatment Selection Algorithm

Step 1: Initial Assessment and Severity Determination

• Confirm diagnosis using DSM-5 criteria: at least 5 symptoms over 2 weeks including depressed mood or anhedonia, plus symptoms such as sleep disturbance, appetite changes, psychomotor changes, fatigue, worthlessness, concentration difficulties, or suicidal ideation 2, 3
• Assess severity using validated tools: PHQ-9, HAM-D, or MADRS 2
• Screen for suicidality, substance use (particularly alcohol), and medical comorbidities 2

Step 2: Choose Initial Treatment Based on Shared Decision-Making

Both CBT and SGAs have similar response rates (RR 0.90, CI 0.76-1.07) and remission rates (RR 0.98, CI 0.73-1.32) based on moderate-quality evidence. 1

Option A: Cognitive Behavioral Therapy

• CBT has equivalent effectiveness to antidepressants with lower discontinuation rates due to adverse events 1
• CBT demonstrates lower relapse rates compared to SGAs 1
• Consider CBT as first-line when: patient preference favors non-pharmacologic treatment, concerns about medication side effects, or availability of trained therapist 1, 2

Option B: Second-Generation Antidepressants

• Start with SSRIs (e.g., fluoxetine, sertraline) or SNRIs as first-line pharmacotherapy 2, 4
• Initial dosing for fluoxetine: 20 mg daily in the morning 3
• For pediatric patients: start 10 mg daily, increase to 20 mg after 1 week (lower weight children may remain at 10 mg) 3
• Maximum dose: 80 mg/day 3
• Full therapeutic effect requires 4-6 weeks minimum 3, 5

Selection between specific SGAs should prioritize adverse effect profiles: 1

• Bupropion: lower sexual dysfunction rates
• Paroxetine: higher sexual dysfunction rates
• Consider drug interactions, particularly with CYP3A4 substrates 1

Step 3: Monitoring and Response Assessment

• Assess response within 1-2 weeks of initiation for adverse effects and suicidality 2, 4
• Define treatment response as ≥50% reduction in severity scores (PHQ-9, HAM-D, MADRS) 2, 4
• If inadequate response by 6-8 weeks, modify treatment 2, 4

Step 4: Second-Line Strategies for Non-Responders

When patients fail to respond adequately after 6-8 weeks of appropriate first-line treatment: 1

Three equivalent options exist (choose based on patient factors):

• Switch to a different antidepressant 1
• Switch to cognitive therapy 1
• Augment current treatment with medication or cognitive therapy 1

The critical decision is simply implementing a different evidence-based strategy rather than the specific choice of strategy. 1

Step 5: Treatment Duration

Acute phase (6-12 weeks): Achieve symptom reduction 2, 4

Continuation phase: 2, 4, 3

• First episode: Continue 4-9 months after satisfactory response
• Recurrent episodes: Continue ≥1 year

Maintenance phase (≥1 year): For patients with multiple episodes 2, 4

Critical Pitfalls to Avoid

• Inadequate dosing or premature discontinuation before 4-6 weeks: Full therapeutic effects require minimum 4 weeks, often longer 3, 5
• Failure to monitor suicidality during initial treatment period: Close monitoring is essential, particularly in first 1-2 weeks 2, 4
• Not continuing treatment long enough: Minimum 4-9 months after response prevents relapse 2, 4, 3
• Waiting too long to modify treatment: If no response by 6-8 weeks with adequate dosing, change strategy 2, 4
• Overlooking alcohol abuse: Up to 30% of depressed patients abuse alcohol; abstinence is crucial for treatment success 6

Special Populations

Severe depression with high-risk features: Initiate antidepressants immediately with close monitoring regardless of symptom count 2

Elderly patients: Consider lower or less frequent dosing 3

Hepatic impairment: Reduce dose or frequency 3

Comorbid anxiety: SSRIs or SNRIs remain first-line; both CBT and pharmacotherapy are effective 4

MAOI Considerations

• Allow 14 days between MAOI discontinuation and fluoxetine initiation 3
• Allow 5 weeks after stopping fluoxetine before starting MAOI 3