What is the recommended assessment and treatment approach for major depressive disorder?

Approach to Major Depressive Disorder

Initial Assessment and Diagnosis

Begin by confirming the diagnosis using DSM-5 criteria: at least 5 symptoms present for ≥2 weeks, including either depressed mood or anhedonia, plus symptoms from insomnia/hypersomnia, weight changes, psychomotor changes, fatigue, worthlessness/guilt, concentration problems, or suicidal ideation. 1, 2

• Use standardized screening tools (PHQ-9, HAM-D, or MADRS) to quantify baseline severity and establish whether depression is mild, moderate, or severe 2, 3
• Conduct direct interviews with both patient and family/caregivers to assess functional impairment across school/work, home, and social domains 1
• Screen for comorbid conditions including anxiety disorders, substance use disorders, and bipolar disorder, as these substantially affect prognosis and treatment selection 1, 2
• Perform immediate suicide risk assessment in every patient, including specific plans, intent, recent attempts, psychotic symptoms, and family history of bipolar disorder or suicide 1

Severity-Based Treatment Algorithm

Mild Depression (5-6 symptoms, minimal functional impairment)

Start with cognitive behavioral therapy (CBT) alone as first-line treatment—antidepressants show virtually no benefit over placebo in mild depression and should not be prescribed. 2, 4

• CBT demonstrates equivalent effectiveness to antidepressants with moderate-quality evidence while avoiding medication adverse effects 1, 2
• Consider watchful waiting with close monitoring if symptoms are very recent onset 5

Moderate Depression (7-8 symptoms, moderate functional impairment)

Initiate either CBT or a second-generation antidepressant (SSRI or SNRI) as monotherapy—both have equivalent effectiveness based on moderate-quality evidence. 1, 2

• Select SSRIs (escitalopram, sertraline, citalopram) as first-line pharmacotherapy due to favorable tolerability profiles 2, 3
• SNRIs (venlafaxine, duloxetine) are slightly more effective than SSRIs but carry higher rates of nausea and vomiting 2
• Base medication selection on adverse effect profiles, cost, and patient preference rather than efficacy differences 1, 2

Severe Depression (≥9 symptoms, severe functional impairment, or any high-risk features)

Immediately initiate combination therapy with both an antidepressant AND CBT—this approach nearly doubles remission rates (57.5% vs 31.0%) compared to antidepressant monotherapy. 2

• High-risk features requiring immediate severe classification regardless of symptom count: specific suicide plan/intent/recent attempt, psychotic symptoms, or first-degree family history of bipolar disorder 1
• Start SSRI or SNRI concurrently with CBT, not sequentially 2
• Consider hospitalization if acute safety concerns exist 1

Safety Planning (Required for ALL Patients)

Establish a written safety plan at the first visit that includes: (1) restricting access to lethal means, (2) identifying a concerned third party who can monitor the patient, and (3) developing an emergency communication mechanism. 1

• Discuss limits of confidentiality explicitly with patient and family 1
• Safety concerns are highest during the initial treatment period and require closest monitoring 1

Treatment Monitoring Protocol

Assess response within 1-2 weeks of treatment initiation, specifically monitoring for therapeutic effects, adverse effects, and emergence of suicidality. 2, 4

• Define response as ≥50% reduction in PHQ-9 or HAM-D scores 2
• If inadequate response by 6-8 weeks, modify treatment through dose adjustment, switching to a different antidepressant, or adding augmentation with buspirone or bupropion SR 2, 4
• For treatment-resistant depression (failure of ≥2 adequate trials), add CBT to ongoing pharmacotherapy or consider switching strategies 2

Treatment Duration

Continue treatment for minimum 4-9 months after achieving remission for first episodes; patients with recurrent depression require ≥1 year or longer. 2, 4

• An adequate antidepressant trial requires minimum 4 weeks at therapeutic dose before declaring failure 2
• Depression follows three phases: acute (6-12 weeks), continuation (4-9 months), and maintenance (≥1 year for recurrent cases) 2

Critical Pitfalls to Avoid

• Never prescribe antidepressants for mild depression—drug-placebo differences are nonexistent in this population 2, 4
• Never discontinue treatment prematurely—therapeutic effects typically require 4-6 weeks minimum, and premature discontinuation dramatically increases relapse risk 2, 4
• Never assume adherence—up to 50% of MDD patients demonstrate non-adherence, which masquerades as treatment resistance; consider checking plasma levels if uncertain 2
• Never skip the suicide risk assessment—this must be performed at every visit, especially during initial treatment when risk peaks 1, 2

Evidence-Based Adjunctive Options

For patients with inadequate response to first-line therapy, acupuncture as an adjunct to antidepressants increases remission rates (35.7% vs 26.1%, RR 1.45) with moderate-certainty evidence 2. Supervised aerobic exercise achieves remission comparable to sertraline with lower discontinuation rates 2. Other complementary approaches (St. John's Wort, omega-3 fatty acids, SAMe, psychobiotics) lack sufficient evidence for recommendation 2.