Internal MedicinePsychiatryMajor Depressive Disorder

Major Depressive Disorder

Must-Not-Miss / Red Flags

  • Suicidal ideation with plan: requires immediate psychiatric evaluation
  • Catatonia: stupor, mutism, posturing – medical emergency (benzodiazepines ± ECT)
  • Psychotic features: mood‑congruent delusions (guilt, nihilism)
Patient Explanation
“Depression is a real medical condition, not a weakness. It affects brain chemistry and can make you feel sad, tired, and hopeless. Treatment works, and we’ll help you through this.”
Board Fact
“SSRIs take 4‑6 weeks to reach full therapeutic effect, but side effects appear immediately – counsel patients and provide bridge support.”
ICD-10
F32.9

Definition & Core Concept

Major Depressive Disorder (MDD) is a common psychiatric illness characterized by persistent low mood, anhedonia, and neurovegetative symptoms lasting ≥2 weeks, causing significant functional impairment.

Epidemiology & Risk Factors

  • Lifetime prevalence: 17% in the US
  • Female‑to‑male ratio 2:1
  • Leading cause of disability worldwide (WHO)
  • Peak onset age: 20‑30 years

Pathophysiology (Rule of 3)

  1. Monoamine hypothesis: deficiency of serotonin, norepinephrine, and dopamine in limbic circuits
  2. Hypothalamic‑pituitary‑adrenal (HPA) axis dysregulation → elevated cortisol
  3. Neuroinflammation and reduced BDNF → impaired neurogenesis in the hippocampus

Clinical Presentation

  • SIGECAPS: Sleep disturbance, Interest loss, Guilt, Energy loss, Concentration difficulty, Appetite change, Psychomotor changes, Suicidal thoughts
  • Diurnal variation (worse in the morning)
  • Somatic complaints: chronic pain, GI upset, fatigue

Diagnostic Workup

PHQ‑9: screening and severity assessment. Clinical interview using DSM‑5‑TR criteria (≥5 of 9 symptoms, including depressed mood or anhedonia). Rule out medical causes: TSH, CBC, Vitamin B12, Vitamin D.

Management Protocol

  1. Mild depression: psychotherapy (CBT) alone
  2. Moderate‑severe: SSRI (Escitalopram 10‑20 mg or Sertraline 50‑200 mg) + psychotherapy
  3. Treatment‑resistant: switch to SNRI, augment with atypical antipsychotic (Aripiprazole), or consider ECT/TMS
  4. Close follow‑up: weekly during initiation, assess suicide risk at every visit

Complications & Prognosis

  • Suicide (15% lifetime risk in severe MDD)
  • Substance use disorder (self‑medication)
  • Increased cardiovascular mortality
  • Treatment‑resistant depression

ICU Criteria

ICU admission for catatonia (risk of rhabdomyolysis, aspiration) or severe suicide attempt.

Clinical Vignette

A 28‑year‑old woman presents with 3 months of low mood, anhedonia, early morning awakening, and 10‑lb weight loss. She feels guilty and worthless. PHQ‑9 score is 22. No previous psychiatric history. TSH and CBC are normal.

Pearls & Pitfalls

  • Always ask about bipolar disorder before starting an antidepressant – SSRIs can trigger mania.
  • SSRI discontinuation syndrome (FINISH: Flu‑like, Insomnia, Nausea, Imbalance, Sensory disturbance, Hyperarousal) mimics recurrence.

Discharge & Follow-Up

Biweekly follow‑up initially, then monthly. Continue antidepressants for at least 6‑12 months after remission. Taper gradually to avoid discontinuation syndrome.

Literature & Guidelines

APA Practice Guideline for the Treatment of Patients with Major Depressive Disorder (2024). PMID: 37973830.

Personal Clinical Notes