What is the approach to assessing and treating Major Depressive Disorder (MDD)?

Assessing Major Depressive Disorder

Diagnostic Criteria

MDD requires at least 5 symptoms present during a 2-week period, with at least one being either depressed mood or loss of interest/pleasure (anhedonia), causing functional impairment. 1, 2

The complete symptom list includes:

• Depressed mood or anhedonia (at least one required) 1, 2
• Significant weight change or appetite disturbance 1
• Insomnia or hypersomnia 1
• Psychomotor agitation or retardation 1
• Fatigue or loss of energy 1
• Feelings of worthlessness or excessive/inappropriate guilt 1
• Diminished concentration or indecisiveness 1
• Recurrent thoughts of death or suicidal ideation 1

Assessment Approach

Use structured diagnostic interviews based on DSM-5 criteria, such as the Mini International Neuropsychiatric Interview or Structured Clinical Interview, to establish the diagnosis. 2

Severity Assessment Tools

Implement the Patient Health Questionnaire-9 (PHQ-9) or Hamilton Depression Rating Scale (HAM-D) to quantify baseline severity and monitor treatment response. 1, 2

Additional validated instruments include:

• Montgomery-Åsberg Depression Rating Scale (MADRS) 2
• Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) 2

Treatment response is defined as ≥50% reduction in severity scores. 1, 2

Critical Differential Diagnoses to Exclude

Systematically assess for conditions that mimic or co-occur with MDD: 3

• Persistent Depressive Disorder (Dysthymia): Chronic symptoms lasting ≥2 years but not meeting full MDD criteria 3
• Adjustment Disorder with Depressed Mood: Depressive symptoms within 3 months of identifiable stressor 3
• Anxiety Disorders: High comorbidity with overlapping symptoms (insomnia, fatigue, concentration difficulties) 3
• Post-Traumatic Stress Disorder: Shares anhedonia, sleep disturbance, and concentration problems 3
• Eating Disorders: Frequently co-occur with depressive symptoms 3

Information Gathering

Conduct direct patient interviews focusing on symptom onset, duration, severity patterns, and functional impairment across multiple settings (work, social, family). 3

Obtain collateral information from family members or other observers when available, as patients may not clearly identify depressed mood as their primary complaint. 3

Severity Classification

Classify severity based on symptom count, intensity, and degree of functional impairment: 2

• Mild: Minimal functional impairment
• Moderate: Intermediate functional impairment
• Severe: Marked functional impairment or presence of psychotic features

Classify as severe regardless of symptom count when high-risk features are present (active suicidality, psychosis, severe functional impairment). 2

Treatment Selection Based on Severity

Mild Depression

For mild MDD, initiate cognitive behavioral therapy (CBT) alone as first-line treatment, as it demonstrates equivalent effectiveness to antidepressants with lower discontinuation rates due to adverse events. 1, 2

Moderate to Severe Depression

For moderate to severe MDD, initiate either CBT or second-generation antidepressants (SGAs), selecting based on adverse effect profiles, cost, accessibility, and patient preferences. 1, 2

Both CBT and SGAs have similar effectiveness as first-line treatments based on moderate-quality evidence. 2

Pharmacotherapy Specifics

Start with SSRIs or SNRIs as first-line pharmacological agents. 2

For sertraline specifically:

• Initial dose: 50 mg once daily for MDD 4
• Dose range: 50-200 mg/day based on response 4
• Allow minimum 1 week between dose adjustments due to 24-hour elimination half-life 4

For venlafaxine:

• Indicated for major depressive disorder treatment 5
• Efficacy established in 6-week controlled trials 5

Severe Depression with High-Risk Features

Initiate antidepressants immediately with close monitoring for suicidality, especially during the initial treatment period. 2

Treatment Monitoring

Assess response within 1-2 weeks of treatment initiation, monitoring for therapeutic effects, adverse effects, and suicidality. 2

If inadequate response by 6-8 weeks, modify treatment through dose adjustment, switching agents, or adding augmentation strategies. 2

Treatment Duration

Continue treatment for 4-9 months after satisfactory response for first episodes. 2, 4

For recurrent episodes, continue treatment for ≥1 year (maintenance phase). 2

The three treatment phases are: 1, 2

• Acute phase: 6-12 weeks
• Continuation phase: 4-9 months
• Maintenance phase: ≥1 year

Common Pitfalls to Avoid

Do not discontinue treatment prematurely before therapeutic effects are achieved (typically 4-6 weeks minimum). 2

Do not use inadequate dosing or fail to titrate to therapeutic levels. 2

Do not fail to monitor for suicidality, particularly during initial treatment and dose changes. 2

Do not stop treatment too early—minimum 4-9 months after response is required to prevent relapse. 2