Major Depressive Disorder (MDD): A Comprehensive Guide

A serious mood disorder characterized by persistent sadness and loss of interest


1. Definition & Diagnostic Criteria (DSM-5)

MDD requires ≥5 symptoms for ≥2 weeks, with at least one being:
✅ Depressed mood (most of the day, nearly every day) OR
✅ Markedly diminished interest/pleasure (anhedonia)

Other Symptoms:
• Significant weight change (±5% in month)
• Insomnia/hypersomnia
• Psychomotor agitation/retardation
• Fatigue/loss of energy
• Worthlessness/excessive guilt
• Diminished concentration
• Recurrent thoughts of death

Key Specifiers:

  • Severity: Mild, Moderate, Severe
  • Features: Psychotic, Melancholic, Atypical, Catatonic
  • Course: Seasonal Pattern, Peripartum Onset

2. Clinical Presentation

Symptom DomainManifestations
EmotionalHopelessness, irritability
CognitiveIndecisiveness, memory lapses
PhysicalChronic pain, digestive issues
BehavioralSocial withdrawal, neglect of duties

High-Risk Signs:
• Suicidal ideation (10-15% mortality if untreated)
• Psychotic features (mood-congruent delusions)


3. Causes & Risk Factors

CategoryExamples
Biological• Serotonin/norepinephrine dysfunction
• Hippocampal atrophy
• Family history (2-3× risk)
Psychological• Early trauma
• Negative cognitive style
Environmental• Chronic stress
• Social isolation

Myth Buster:
❌ “It’s just laziness” → Neurobiological basis confirmed by fMRI/PET studies


4. Diagnosis & Assessment

Differential Diagnosis:
• Bipolar Depression (screen for hypomania)
• Medical causes (hypothyroidism, vitamin D deficiency)

Rating Scales:
• PHQ-9 (Primary Care)
• MADRS (Research Settings)

Lab Tests:
• TSH, CBC, Metabolic Panel (rule out mimics)


5. Evidence-Based Treatments

A. Pharmacotherapy

ClassExamplesKey Considerations
SSRIsEscitalopram, SertralineFirst-line; GI side effects
SNRIsVenlafaxine, DuloxetineHelpful for comorbid pain
Atypical ADsBupropion, MirtazapineLess sexual dysfunction/weight gain

B. Psychotherapy
• CBT: Challenges cognitive distortions
• IPT: Addresses interpersonal stressors
• Behavioral Activation: Breaks avoidance cycles

C. Advanced Options
• rTMS (for treatment-resistant cases)
• Ketamine/Esketamine (rapid suicidality reduction)


6. Prognosis & Course

• 50-60% relapse rate after first episode
• Recurrence risk ↑ with each episode (kindling hypothesis)
• Full remission possible with early intervention


7. Special Populations

GroupClinical Pearls
AdolescentsIrritability > sadness; screen for self-harm
ElderlyMay present as “pseudodementia”
Peripartum10-15% prevalence; requires urgent treatment