Major Depressive Disorder
Summary
Major Depressive Disorder (MDD) is a common, serious mood disorder characterised by persistent low mood, anhedonia (loss of pleasure), and associated cognitive, behavioural, and physical symptoms. Affecting approximately 5% of the adult population globally, depression is a leading cause of disability worldwide. The diagnosis requires symptoms to be present for at least two weeks and to cause significant functional impairment. Treatment involves a biopsychosocial approach: antidepressants (SSRIs first-line), psychological therapy (CBT, IPT), and addressing social factors. Early recognition and treatment significantly improves outcomes.
Key Facts
- Prevalence: 5-7% lifetime prevalence in adults
- Sex Ratio: 2:1 female to male
- Peak Onset: 20s-30s, but can occur at any age
- Recurrence: 50% after first episode, 80% after two episodes
- Disability: Leading cause of disability worldwide (WHO)
- Mortality: 15-fold increased suicide risk; increased cardiovascular mortality
- Treatment Response: 60-70% respond to first antidepressant
Clinical Pearls
High-Yield Points:
- Always assess suicide risk directly and thoroughly
- Core symptoms: Low mood, Anhedonia, Anergia (lack of energy)
- Biological symptoms suggest severity: early morning wakening, diurnal variation, psychomotor changes
- SSRIs take 2-4 weeks for effect; warn patients about this delay
- Combination of medication + therapy is more effective than either alone
- Rule out organic causes: hypothyroidism, anaemia, medication-induced
Why This Matters Clinically
Depression is one of the most common conditions encountered in primary care and all medical specialties. Untreated depression increases mortality from suicide and comorbid medical conditions. Depression worsens outcomes in cardiovascular disease, diabetes, and cancer. Early recognition and evidence-based treatment can be life-saving.
Prevalence and Incidence
| Metric | Value |
|---|---|
| Lifetime Prevalence | 15-20% |
| Point Prevalence | 5-7% |
| Incidence | 3% per year |
| Gender Ratio | Female:Male 2:1 |
Risk Factors
Non-Modifiable:
- Female sex
- Family history of depression (2-3x increased risk)
- Personal history of depression
- Adverse childhood experiences
Modifiable:
- Social isolation and loneliness
- Unemployment
- Chronic medical illness
- Substance misuse (alcohol, cannabis)
- Sleep disturbance
Precipitating Factors:
- Major life events (bereavement, relationship breakdown)
- Physical illness diagnosis
- Postpartum period
- Medication (beta-blockers, steroids, isotretinoin)
Biological Models
Monoamine Hypothesis:
- Reduced serotonin, norepinephrine, and dopamine neurotransmission
- Basis for SSRI, SNRI, and TCA mechanisms
- Oversimplified but clinically useful model
Neuroplasticity Model:
- Reduced BDNF (brain-derived neurotrophic factor)
- Hippocampal volume reduction
- Impaired neurogenesis
HPA Axis Dysregulation:
- Chronic stress leads to cortisol elevation
- Hippocampal damage and feedback loop disruption
Inflammation:
- Elevated inflammatory markers (IL-6, CRP)
- Bidirectional relationship with physical illness
Psychological Models
- Cognitive Model (Beck): Negative automatic thoughts, cognitive distortions
- Learned Helplessness (Seligman): Belief in inability to control outcomes
- Behavioural Model: Reduced positive reinforcement from environment
Diagnostic Criteria (ICD-11 / DSM-5)
Core Symptoms (at least one required):
- Depressed mood (most of the day, nearly every day)
- Anhedonia (loss of interest or pleasure)
Additional Symptoms (5 or more total including core): 3. Weight/appetite change (increase or decrease) 4. Sleep disturbance (insomnia or hypersomnia) 5. Psychomotor agitation or retardation 6. Fatigue or loss of energy 7. Feelings of worthlessness or excessive guilt 8. Concentration difficulties, indecisiveness 9. Recurrent thoughts of death or suicide
Duration: ≥2 weeks
Impact: Causes significant distress or functional impairment
Biological Symptoms (Indicate Severity)
Severity Classification
| Severity | Symptom Count | Function |
|---|---|---|
| Mild | 5 symptoms | Minor impairment |
| Moderate | 6-7 symptoms | Moderate impairment |
| Severe | 8-9 symptoms | Marked impairment, may have psychotic features |
Psychotic Depression
Mental State Examination
| Domain | Findings in Depression |
|---|---|
| Appearance | Unkempt, poor self-care, reduced eye contact |
| Behaviour | Psychomotor retardation or agitation |
| Speech | Reduced rate and volume, increased latency |
| Mood | "Low", "hopeless", "empty" (subjective) |
| Affect | Flattened, restricted, tearful |
| Thought Content | Guilt, worthlessness, hopelessness, suicidal ideation |
| Cognition | Poor concentration ("pseudodementia" in severe cases) |
| Insight | Usually preserved |
Risk Assessment (ESSENTIAL)
Suicide Risk Factors:
- Previous suicide attempt (strongest predictor)
- Current suicidal ideation with plans/intent
- Access to means
- Male sex, older age
- Social isolation
- Recent loss
- Comorbid substance misuse
- Hopelessness
Protective Factors:
- Social support
- Dependent children
- Religious beliefs
- Therapeutic alliance
Purpose: Rule Out Organic Causes
| Investigation | Rationale |
|---|---|
| FBC | Anaemia, infection |
| TFTs | Hypothyroidism |
| LFTs | Alcohol misuse |
| U&Es, Glucose | Metabolic causes |
| Calcium | Hypercalcaemia |
| B12, Folate | Deficiency |
| Drug Screen | Substance-induced |
Rating Scales (Severity Monitoring)
- PHQ-9: 9 questions, scores 0-27 (Mild 5-9, Moderate 10-14, Severe ≥15)
- HAMD: Hamilton Depression Rating Scale (clinician-rated)
- BDI: Beck Depression Inventory
NICE Stepped Care Model
Step 1 (Sub-threshold/Mild):
- Assessment and active monitoring
- Self-help resources, exercise
- Sleep hygiene
Step 2 (Mild-Moderate):
- Low-intensity psychological intervention (guided self-help, computerised CBT)
- Exercise programmes
Step 3 (Moderate-Severe):
- High-intensity psychological therapy (CBT, IPT, BA)
- Antidepressant medication
Step 4 (Severe/Complex/Treatment-Resistant):
- Specialist mental health services
- Crisis teams
- Inpatient care if high risk
Pharmacological Treatment
First-Line: SSRIs
| Drug | Starting Dose | Target Dose | Notes |
|---|---|---|---|
| Sertraline | 50 mg OD | 100-200 mg | NICE first choice, safe in cardiac disease |
| Fluoxetine | 20 mg OD | 20-60 mg | Long half-life, activating |
| Citalopram | 10-20 mg OD | 20-40 mg | QTc prolongation risk, max 20mg if >5 |
| Escitalopram | 5-10 mg OD | 10-20 mg | Potent, well tolerated |
Second-Line/Alternatives:
| Class | Examples | When to Use |
|---|---|---|
| SNRI | Venlafaxine, Duloxetine | SSRI failure, pain comorbidity |
| Mirtazapine | 15-45 mg | Insomnia, weight loss, nausea with SSRIs |
| TCA | Amitriptyline | Specialist use, chronic pain |
Treatment Principles:
- Start low, go slow (50% dose initially)
- Allow 2-4 weeks for effect
- Continue 6-9 months after remission (first episode)
- 2+ years if recurrent depression
- Taper slowly when stopping (discontinuation syndrome)
Psychological Therapies
| Therapy | Evidence | Format |
|---|---|---|
| CBT | Strong (NICE recommended) | 12-16 sessions |
| IPT | Strong | 12-16 sessions |
| Behavioural Activation | Strong | Focuses on activity scheduling |
| Counselling | Moderate | Supportive |
Electroconvulsive Therapy (ECT)
Indications:
- Severe depression with life-threatening features (severe self-neglect, catatonia)
- Psychotic depression
- Treatment-resistant depression
- Rapid response needed
Efficacy: 70-80% response rate in severe depression
Resistant Depression (After 2+ Adequate Trials)
- Augmentation: Add lithium or aripiprazole
- Switch antidepressant class
- Ketamine/esketamine (specialist)
- ECT
- TMS (repetitive transcranial magnetic stimulation)
Acute
| Complication | Risk | Management |
|---|---|---|
| Suicide | 15% lifetime in severe | Risk assessment, crisis plan |
| Self-harm | Common | Safety planning |
| Psychosis | 10-15% of severe cases | Antipsychotic + AD |
Chronic
- Recurrent episodes (80% after 2 episodes)
- Treatment-resistant depression (30%)
- Functional impairment (work, relationships)
- Cardiovascular disease (2x risk)
- Substance misuse (comorbid in 30%)
Natural History
- Episode Duration: 6-12 months untreated
- With Treatment: Remission in 60-70% within 6 months
- Recurrence: 50% after first episode
Prognostic Factors
Poor Prognosis:
- Severe initial episode
- Psychotic features
- Chronic duration
- Comorbid personality disorder
- Poor social support
- Substance misuse
Good Prognosis:
- Acute onset
- Clear precipitant
- Good premorbid function
- Strong social support
- Treatment adherence
Key Guidelines
| Guideline | Organisation | Year |
|---|---|---|
| Depression in Adults | NICE CG90 | 2009 (Updated 2022) |
| APA Practice Guideline | APA | 2019 |
| CANMAT Guidelines | Canadian Network | 2023 |
Key Evidence
- STAR*D: Large trial showing ~33% remission with first SSRI, cumulative 67% over 4 steps
- COMBINE Studies: Psychological + pharmacological = best outcomes
What is Depression?
Depression is more than just feeling sad – it's a medical condition that affects how you think, feel, and function. It involves changes in brain chemistry and can happen to anyone. The key symptoms are feeling persistently low and losing interest in things you used to enjoy.
What causes it?
Depression is caused by a combination of factors:
- Brain chemistry: Changes in mood-regulating chemicals
- Genetics: Runs in families
- Life events: Stress, loss, trauma
- Physical illness: Chronic conditions can trigger depression
How is it treated?
Treatment works well for most people:
- Talking therapies: Like CBT, help change unhelpful thought patterns
- Medication: Antidepressants correct chemical imbalances (not addictive)
- Lifestyle: Exercise, sleep, social connection all help
- Most people feel better within 2-3 months with proper treatment
When to seek urgent help
Go to A&E or call 999 if you or someone else:
- Has thoughts of suicide or self-harm
- Has made a plan to end their life
- Feels unable to keep themselves safe
Helplines: Samaritans 116 123 (UK, free, 24/7)
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NICE. Depression in adults: treatment and management (CG90). 2022. nice.org.uk
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American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 2019. psychiatryonline.org
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Kennedy SH, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines. Can J Psychiatry. 2016;61(9):540-560. PMID: 27486148
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Rush AJ, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps (STAR*D). Am J Psychiatry. 2006;163(11):1905-1917. PMID: 17074942
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. It does not replace professional medical judgement. Always verify critical information and consider individual patient factors.