Major Depressive Disorder

MDD Basics - Deep Dive Diagnosis

• Definition: Persistent low mood or anhedonia causing significant distress/impairment; common, often recurrent.
• DSM-5 Criteria: $\ge$ 5 of 9 symptoms in same 2-week period; must include (1) depressed mood or (2) anhedonia (loss of interest/pleasure).
  • 📌 SIGECAPS:
    • Sleep disturbance (insomnia/hypersomnia)
    • Interest decreased (anhedonia)
    • Guilt or worthlessness
    • Energy decreased (fatigue)
    • Concentration difficulties
    • Appetite change (↑/↓) or weight change ($\ge$ 5%/month)
    • Psychomotor agitation/retardation
    • Suicidal ideation/thoughts
• Symptoms cause clinically significant distress or functional impairment.
• Not attributable to substance use or another medical condition. Episode not better explained by a psychotic disorder. No history of manic/hypomanic episode.

⭐ MDD is approximately twice as common in women as in men, a finding consistent across many cultures and countries.

Etiopathogenesis - Brain's Blue Notes

• Biological Factors:
  • Monoamine Hypothesis: ↓ Serotonin (5-HT), ↓ Norepinephrine (NE), ↓ Dopamine (DA).
  • Neuroendocrine:
    • Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity: ↑ Cortisol; Dexamethasone Suppression Test (DST) non-suppression.
    • Thyroid dysfunction (e.g., hypothyroidism).
  • Neuroinflammation: ↑ Pro-inflammatory cytokines (e.g., IL-6, TNF-α).
  • Genetics:
    • Heritability approx. ~37%.
    • Gene-environment interaction (e.g., 5-HTTLPR polymorphism & stress).
  • Brain Structural & Functional Changes: ↓ Hippocampal volume; altered Prefrontal Cortex (PFC), amygdala, Anterior Cingulate Cortex (ACC) activity.
• Psychosocial Factors:
  • Stressful life events (e.g., loss, trauma, abuse).
  • Early life adversity.
  • Personality traits (e.g., neuroticism, introversion).
  • Cognitive theory (Beck's cognitive triad: negative view of self, world, future).

⭐ HPA axis dysregulation, particularly hypercortisolemia and non-suppression on the Dexamethasone Suppression Test (DST), is a well-documented biological finding in many patients with MDD.

Clinical Features & Diagnosis - Symptom Spotlight

• Core Criteria (DSM-5): ≥5 of 9 symptoms for ≥2 weeks; must include (1) depressed mood OR (2) anhedonia.
• 📌 SIGECAPS Mnemonic:
  • Sleep disturbance (↑/↓)
  • Interest loss (↓, anhedonia)
  • Guilt (excessive, worthlessness)
  • Energy loss (↓, fatigue)
  • Concentration difficulties (↓, indecisiveness)
  • Appetite change (↑/↓, weight change >5%/month)
  • Psychomotor agitation/retardation (observable)
  • Suicidal thoughts/ideation
• Key Exclusions: Symptoms not due to substance, other medical condition, or better explained by other psychotic disorders. Crucially, no history of mania/hypomania.
• Common Specifiers:
  • Atypical features (mood reactivity, weight gain, hypersomnia, leaden paralysis, rejection sensitivity)
  • Melancholic features (severe anhedonia, early morning awakening, diurnal variation worse AM, guilt)
  • Psychotic features (delusions/hallucinations)
  • Anxious distress

⭐ MDD with psychotic features often requires combination treatment with an antidepressant and an antipsychotic, or Electroconvulsive Therapy (ECT).

Management - Mood Menders

• Principles: Stepped care; aim for remission. Combine pharmacotherapy & psychotherapy.
• Pharmacotherapy:
  • SSRIs (e.g., Fluoxetine): 1st line; SEs: GI, sexual.
  • SNRIs (e.g., Venlafaxine).
  • TCAs (e.g., Amitriptyline): Cardiotoxic, anticholinergic.
  • MAOIs (e.g., Phenelzine): Hypertensive crisis risk.
  • Augment/switch if poor response.
• Psychotherapy: CBT, IPT.
• Somatic Therapies:
  • ECT: Severe, treatment-resistant, psychotic MDD, catatonia, high suicide risk.
  • rTMS: For non-response.
• Duration: Continue antidepressants 6-9 months post-remission.

⭐ ECT is the most effective treatment for severe MDD, especially with psychotic features or high suicide risk. It is considered the safest psychotropic intervention during pregnancy.

High‑Yield Points - ⚡ Biggest Takeaways

• Core symptoms: Depressed mood or anhedonia for ≥2 weeks is essential for diagnosis.
• Use SIGECAPS mnemonic for common associated symptoms.
• SSRIs (e.g., Fluoxetine, Escitalopram) are first-line pharmacotherapy.
• ECT is indicated for severe/treatment-resistant depression, active suicidality, or catatonia.
• Key risk factors include female gender, family history, and stressful life events.
• Suicide risk assessment is paramount in all patients with MDD.
• Differentiate from Persistent Depressive Disorder (chronic depression, ≥2 years).