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 Domain | Manifestations |
|---|---|
| Emotional | Hopelessness, irritability |
| Cognitive | Indecisiveness, memory lapses |
| Physical | Chronic pain, digestive issues |
| Behavioral | Social withdrawal, neglect of duties |
High-Risk Signs:
• Suicidal ideation (10-15% mortality if untreated)
• Psychotic features (mood-congruent delusions)
3. Causes & Risk Factors
| Category | Examples |
|---|---|
| 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
| Class | Examples | Key Considerations |
|---|---|---|
| SSRIs | Escitalopram, Sertraline | First-line; GI side effects |
| SNRIs | Venlafaxine, Duloxetine | Helpful for comorbid pain |
| Atypical ADs | Bupropion, Mirtazapine | Less 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
| Group | Clinical Pearls |
|---|---|
| Adolescents | Irritability > sadness; screen for self-harm |
| Elderly | May present as “pseudodementia” |
| Peripartum | 10-15% prevalence; requires urgent treatment |