Major depressive disorder

Major Depressive Disorder (MDD) is a common and serious mood disorder characterized by persistent depressed mood and/or markedly diminished interest or pleasure in nearly all activities for at least two consecutive weeks. The condition causes clinically significant impairment in social, occupational, educational, and interpersonal functioning.

MDD is associated with substantial morbidity, increased suicide risk, reduced quality of life, and significant global disease burden. It affects individuals across all age groups and frequently coexists with anxiety disorders, substance use disorders, and chronic medical illnesses.

Epidemiology

• Lifetime prevalence: 10–20%

• More common in females (≈2:1 ratio)

• Peak onset: late adolescence to early adulthood

• Recurrence rate exceeds 50% after first episode

Risk Factors

Biological Factors

• Genetic predisposition (family history of depression)

• Neurotransmitter imbalance (serotonin, norepinephrine, dopamine)

• Chronic medical illnesses:

  • Diabetes mellitus

  • Cardiovascular disease

  • Cancer

  • Hypothyroidism

• Hormonal changes (postpartum, menopause)

Psychological Factors

• Low self-esteem

• Negative cognitive patterns

• Childhood trauma or abuse

• Personality vulnerabilities

Social & Environmental Factors

• Bereavement

• Financial stress

• Social isolation

• Relationship conflicts

• Substance misuse

Pathophysiology

MDD involves dysfunction across multiple neurobiological systems:

• Reduced monoamine neurotransmission

• Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis

• Neuroinflammation

• Reduced neuroplasticity and hippocampal volume

• Altered functional connectivity within mood regulation circuits

Signs and Symptoms

Symptoms must persist ≥2 weeks and represent a change from previous functioning.

Psychological Symptoms

• Persistent depressed mood

• Loss of interest or pleasure (anhedonia)

• Feelings of worthlessness

• Excessive guilt

• Hopelessness

• Reduced concentration or indecisiveness

• Recurrent thoughts of death or suicide

Somatic (Neurovegetative) Symptoms

• Appetite or weight change

• Sleep disturbance (insomnia or hypersomnia)

• Psychomotor agitation or retardation

• Fatigue or loss of energy

• Reduced libido

Diagnostic Criteria (DSM-5 Based)

Diagnosis requires ≥5 symptoms present most of the day, nearly every day for ≥2 weeks, including at least one of:

1. Depressed mood

2. Loss of interest or pleasure

Additional symptoms:

• Appetite change

• Sleep disturbance

• Psychomotor changes

• Fatigue

• Worthlessness/guilt

• Poor concentration

• Suicidal ideation

Symptoms must:

• Cause functional impairment

• Not be attributable to substances or medical illness

• Not occur exclusively during psychotic disorders or bipolar disorder

Severity Classification

• Mild

• Moderate

• Severe (with or without psychotic features)

Differential Diagnosis

• Bipolar disorder

• Persistent depressive disorder (dysthymia)

• Adjustment disorder

• Anxiety disorders

• Substance-induced mood disorder

• Hypothyroidism

• Dementia (elderly)

Investigations

Purpose

To exclude medical or substance-related causes.

Recommended Tests

• Full blood count

• Thyroid function tests

• Blood glucose

• Liver and renal function tests

• Vitamin B12 and folate

• Substance use screening

Additional investigations guided by clinical suspicion.

Management

Management combines psychological, pharmacological, and social interventions.

Non-Pharmacological Management

Psychotherapy (First-line for mild–moderate depression)

• Cognitive Behavioural Therapy (CBT)

• Interpersonal Psychotherapy (IPT)

• Behavioural activation therapy

• Problem-solving therapy

• Family or marital therapy

• Stress management and coping skills training

Psychosocial Measures

• Sleep hygiene

• Structured daily activity

• Physical exercise

• Social support enhancement

• Substance cessation

Pharmacological Management

Indicated for:

• Moderate–severe depression

• Functional impairment

• Suicidal risk

• Failure of psychotherapy alone

Adults

Tricyclic Antidepressant

• Amitriptyline (PO) 50–75 mg at night→ Gradually increase to maximum 150 mg/day

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Fluoxetine (PO) 20 mg daily→ Increase up to 60 mg/day

OR

• Fluvoxamine (PO) 50–100 mg daily

OR

• Citalopram (PO) 20 mg daily→ Maximum 60 mg/day

Elderly Patients

• Start low and titrate slowly

Options:

• Amitriptyline 25–50 mg nightly(Maximum 75 mg/day)

OR

• Citalopram maximum 40 mg/day

Treatment Principles

• Initiate at low dose

• Assess response after 4–6 weeks

• Continue treatment 6–12 months after remission

• Recurrent depression may require long-term therapy

• Avoid abrupt discontinuation

Treatment-Resistant Depression

Consider:

• Medication switching

• Combination therapy

• Augmentation strategies

• Specialist psychiatric referral

• Electroconvulsive Therapy (ECT) for severe or suicidal cases

Emergency Management

Immediate psychiatric assessment required if:

• Active suicidal ideation

• Suicide attempt

• Psychotic depression

• Severe functional incapacity

Hospital admission may be necessary.

Complications

• Suicide

• Substance abuse

• Occupational impairment

• Relationship breakdown

• Chronic recurrent depression

• Increased cardiovascular morbidity

Special Populations

Pregnancy & Postpartum

• Prefer psychotherapy when possible

• Risk–benefit evaluation required for medication

Adolescents

• Increased suicide monitoring essential

Elderly

• Higher risk of medication adverse effects

• Depression may mimic dementia

Prevention

• Early identification of at-risk individuals

• Treatment of previous depressive episodes

• Stress reduction strategies

• Substance misuse prevention

• Strengthening social support systems

• Maintenance antidepressant therapy in recurrent cases

Prognosis

• Majority respond to treatment

• 20–30% develop chronic symptoms

• Early treatment improves long-term outcomes

• Relapse common without maintenance therapy

Patient Education

Patients should be advised that:

• Depression is a treatable medical illness

• Medication effects may take 2–4 weeks

• Treatment should not be stopped abruptly

• Regular follow-up improves recovery

• Seek urgent care if suicidal thoughts occur