Major Depressive Disorder (MDD)
A mood disorder characterized by persistent low mood and/or anhedonia with cognitive, somatic, and functional impairment. This page distills diagnostic criteria, specifiers, screening, treatment options, and safety planning.
Diagnostic Criteria (DSM‑5 style)
| Domain | Details |
|---|---|
| Core | ≥ 2 weeks of depressed mood and/or markedly diminished interest/pleasure (anhedonia) most of the day, nearly every day. |
| Additional symptoms | Significant weight/appetite change; sleep disturbance (insomnia/hypersomnia); psychomotor agitation/retardation; fatigue; feelings of worthlessness or excessive guilt; impaired concentration/indecisiveness; recurrent thoughts of death/suicidality. |
| Threshold | ≥ 5 total symptoms (including one core) causing clinically significant distress or functional impairment; not better explained by substances/medical conditions; no mania/hypomania history (else consider bipolar). |
Specifiers & Course
| Specifier | Highlights |
|---|---|
| With anxious distress | Restlessness, tension, fear of losing control; poorer outcomes without treatment. |
| Atypical features | Mood reactivity, hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. |
| Melancholic | Profound anhedonia, diurnal variation (worse AM), early waking, psychomotor changes. |
| Peripartum onset | During pregnancy or within 4 weeks postpartum. |
| Seasonal pattern | Temporal pattern across years (often fall/winter onset). |
| Psychotic features | Mood‑congruent or incongruent delusions/hallucinations. |
| Course | Notes |
|---|---|
| Single vs recurrent | High recurrence risk; consider maintenance therapy after ≥ 2 episodes. |
| Chronicity | Some cases persist >2 years (consider persistent depressive disorder overlap). |
| Comorbidity | Common with anxiety, PTSD, substance use, chronic pain, and medical illness. |
Differential Diagnosis
| Consider | Why / How to Distinguish |
|---|---|
| Bipolar depression | History of mania/hypomania; antidepressant‑induced switching; family history. |
| Medical causes | Hypothyroidism, anemia, sleep apnea, neurodegenerative disease, medications (isotretinoin, steroids, interferon). |
| Grief | Waves of sadness tied to loss with preserved capacity for positive emotion; watch for prolonged grief disorder. |
| Adjustment disorder | Symptom cluster subthreshold and time‑linked to stressor, resolves with adaptation. |
Screening & Measurement
| Tool | Use |
|---|---|
| PHQ‑2 / PHQ‑9 | Screen and quantify severity; track response to treatment. |
| GAD‑7 | Assess comorbid anxiety. |
| Columbia‑Suicide Severity Rating Scale (C‑SSRS) | Structured suicide risk assessment. |
| Baseline workup | Why |
|---|---|
| TSH, CBC, CMP, B12/folate, meds review | Rule out contributors; assess safety before pharmacotherapy. |
| Sleep assessment | OSA/insomnia can maintain symptoms; consider actigraphy/sleep study when indicated. |
Pathophysiology — Brief Overview
| Axis | Key Notes |
|---|---|
| Neurotransmitters | Serotonin, norepinephrine, dopamine network dysfunction; circadian and glutamatergic changes. |
| Neurocircuitry | Frontolimbic dysconnectivity (PFC, amygdala, hippocampus); impaired reward processing. |
| Neuroendocrine | HPA‑axis hyperactivity; sleep architecture disruption. |
| Immunoinflammatory | Elevated cytokines in subsets; sickness‑behavior overlap. |
| Genetics & environment | Polygenic risk + adverse life events; kindling and stress sensitization. |
Treatment Options (Evidence‑Informed)
| Modality | Examples / Notes |
|---|---|
| Psychotherapy | CBT, IPT, BA, ACT; trauma‑focused when indicated; combine with meds for moderate–severe. |
| First‑line meds | SSRIs/SNRIs; start low, titrate; evaluate in 4–6 weeks; manage side‑effects. |
| Atypical agents | Bupropion (activating), mirtazapine (sleep/appetite), vortioxetine, vilazodone. |
| Augmentation | Second agent (e.g., bupropion, mirtazapine); lithium; thyroid; atypical antipsychotics in TRD. |
| Somatic therapies | ECT (severe/psychotic/suicidality), rTMS/theta‑burst, esketamine/ketamine in TRD settings. |
| Lifestyle | Sleep regularity, exercise, Mediterranean‑style diet, substance‑use reduction, bright‑light therapy (seasonal). |
| Monitoring | Key Points |
|---|---|
| Early follow‑up | Side‑effects, activation, suicidality—especially in first 2–4 weeks or dose changes. |
| Response targets | ≥50% symptom reduction by 6–8 weeks; remission preferred; continue meds 6–12 months after remission. |
| Maintenance | Consider long‑term therapy after ≥2–3 episodes or severe course; relapse prevention plan. |
Safety — Red Flags
Seek urgent help (call local emergency number or crisis line) if there is suicidal intent/plan, inability to care for self, psychosis, severe substance use, or rapidly worsening agitation. If on medication, do not stop abruptly without medical guidance.
Relapse Prevention
| Strategy | Practice |
|---|---|
| Early‑warning signs list | Track sleep, anhedonia, rumination, appetite, energy; share with a support person. |
| Routine & rhythm | Consistent wake time, daylight exposure, movement, meals. |
| Booster therapy | Scheduled CBT/IPT boosters; maintain skills work. |
| Medication plan | Do not taper without plan; slow tapers with follow‑up. |
| Social connection | Peer groups, structured activities, purposeful projects. |
Educational content only; not medical advice.