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Saturday, August 16, 2025

Depression in adults


Introduction

Depression, formally known as Major Depressive Disorder (MDD), is a common and disabling psychiatric condition characterized by persistent low mood, loss of interest or pleasure (anhedonia), cognitive impairment, and various physical and emotional symptoms. It is more than normal sadness; depression is a medical illness that interferes with daily functioning, relationships, work, and overall quality of life.

Depression is among the leading causes of disability worldwide. The World Health Organization (WHO) identifies it as a major contributor to the global burden of disease, with significant impact on public health, economics, and social well-being.

Epidemiology

  • Lifetime prevalence: 15–20% in adults.

  • Point prevalence: 5–10% globally.

  • More common in women than men (approx. 2:1 ratio).

  • Can present at any age but peaks in early adulthood (20s–40s).

  • High comorbidity with anxiety disorders, substance use, cardiovascular disease, and diabetes.

  • Major risk for suicide: Up to 15% of severely depressed patients die by suicide.

Etiology and Pathophysiology

Depression is multifactorial, involving biological, psychological, and social influences.

1. Biological Factors

  • Neurotransmitter imbalance: Reduced activity of serotonin, norepinephrine, and dopamine.

  • Hypothalamic–pituitary–adrenal (HPA) axis dysfunction: Hypercortisolemia due to chronic stress.

  • Neuroanatomical changes: Decreased hippocampal volume, altered prefrontal cortex activity.

  • Genetic contribution: Heritability ~40%.

2. Psychological Factors

  • Negative cognitive styles (hopelessness, pessimism).

  • History of trauma, abuse, or neglect.

  • Poor coping skills.

3. Social Factors

  • Chronic stress (financial hardship, unemployment, relationship problems).

  • Social isolation.

  • Lack of supportive environment.

Risk Factors

  • Family history of depression.

  • Previous depressive episode.

  • Chronic medical conditions (diabetes, cancer, cardiovascular disease).

  • Substance abuse.

  • Female gender.

  • Postpartum period.

  • Personality traits (neuroticism, perfectionism).

Clinical Features

1. Core Symptoms

  • Persistent low mood.

  • Anhedonia (loss of interest/pleasure).

  • Fatigue or low energy.

2. Additional Symptoms

  • Changes in appetite or weight (loss or gain).

  • Sleep disturbances (insomnia or hypersomnia).

  • Psychomotor retardation or agitation.

  • Poor concentration, indecisiveness.

  • Feelings of worthlessness, guilt.

  • Suicidal thoughts or behaviors.

3. Subtypes

  • Melancholic depression: Severe anhedonia, diurnal mood variation, early morning awakening.

  • Atypical depression: Mood reactivity, increased appetite/sleep, leaden paralysis.

  • Psychotic depression: Hallucinations or delusions with depressive themes.

  • Seasonal affective disorder (SAD): Occurs during winter months.

  • Persistent depressive disorder (dysthymia): Chronic low-grade depression lasting ≥2 years.

Diagnosis

Diagnosis is clinical, based on standardized criteria.

1. DSM-5 Criteria

  • At least 5 symptoms present for ≥2 weeks, including depressed mood or anhedonia.

  • Symptoms cause significant distress or impairment.

  • Not attributable to substances or another medical condition.

2. Screening Tools

  • Patient Health Questionnaire-9 (PHQ-9).

  • Hamilton Depression Rating Scale (HAM-D).

  • Beck Depression Inventory (BDI).

Complications

  • Suicide and self-harm.

  • Substance misuse.

  • Poor adherence to medical treatments.

  • Worsening of chronic medical conditions.

  • Social isolation and occupational impairment.

Management

Treatment is multimodal: pharmacotherapy, psychotherapy, lifestyle changes, and (in resistant cases) interventional therapies.

1. Non-Pharmacological Approaches

  • Psychoeducation: Involving patients and families.

  • Psychotherapy:

    • Cognitive Behavioral Therapy (CBT).

    • Interpersonal Therapy (IPT).

    • Psychodynamic therapy.

  • Lifestyle modification:

    • Regular physical exercise.

    • Balanced diet.

    • Adequate sleep hygiene.

    • Reduction of alcohol and drug use.

  • Social interventions: Support groups, employment assistance.

2. Pharmacological Therapy

Antidepressants are first-line in moderate to severe depression, or in mild depression unresponsive to psychotherapy.

a) Selective Serotonin Reuptake Inhibitors (SSRIs) – First-line

  • Fluoxetine: 20–60 mg once daily.

  • Sertraline: 50–200 mg once daily.

  • Citalopram: 20–40 mg once daily.

  • Escitalopram: 10–20 mg once daily.

  • Paroxetine: 20–50 mg once daily.

  • Advantages: Better safety profile, lower overdose risk.

b) Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)

  • Venlafaxine: 75–225 mg/day in divided doses.

  • Duloxetine: 30–120 mg once daily.

  • Desvenlafaxine: 50–100 mg once daily.

  • Useful in depression with comorbid anxiety or pain syndromes.

c) Atypical Antidepressants

  • Bupropion hydrochloride: 150–300 mg/day (stimulating, no sexual side effects).

  • Mirtazapine: 15–45 mg at bedtime (sedating, promotes weight gain).

  • Trazodone: 50–150 mg at bedtime (often used for insomnia).

d) Tricyclic Antidepressants (TCAs)

  • Amitriptyline: 75–150 mg/day.

  • Nortriptyline: 50–150 mg/day.

  • Imipramine: 75–200 mg/day.

  • Effective but limited by anticholinergic and cardiotoxic side effects.

e) Monoamine Oxidase Inhibitors (MAOIs)

  • Phenelzine: 15–90 mg/day.

  • Tranylcypromine: 10–60 mg/day.

  • Reserved for refractory depression due to dietary restrictions (tyramine interaction).

3. Treatment-Resistant Depression

  • Combination therapy: SSRI + bupropion or mirtazapine.

  • Augmentation: Lithium (600–1200 mg/day, target serum 0.6–1.0 mmol/L), or atypical antipsychotics (e.g., aripiprazole 2–15 mg/day, quetiapine 50–300 mg/day).

  • Electroconvulsive Therapy (ECT): Effective for severe, resistant, or psychotic depression.

  • Repetitive Transcranial Magnetic Stimulation (rTMS): Non-invasive brain stimulation.

  • Esketamine nasal spray (in selected refractory cases).

4. Duration of Therapy

  • First episode: Continue antidepressant for 6–12 months after remission.

  • Recurrent depression: Consider maintenance therapy for ≥2 years or lifelong.

Prognosis

  • With treatment, ~70% of patients achieve remission.

  • Without treatment, depression is often chronic or recurrent.

  • Early intervention improves long-term outcomes.

  • Recurrence risk:

    • 50% after first episode.

    • 70% after second episode.

    • 90% after three or more episodes.

Suicide Risk

  • Suicide is the most serious complication.

  • Risk factors: male gender, previous attempt, comorbid substance use, severe hopelessness, lack of social support.

  • Suicide risk must always be assessed in clinical practice.

Future Directions

  • Personalized medicine: Using genetic and biomarker testing to guide antidepressant selection.

  • Novel pharmacological targets: Glutamatergic system (ketamine, esketamine), neurotrophic pathways.

  • Digital therapeutics: Telepsychiatry, AI-driven CBT apps.

  • Integrated care models: Combining mental and physical healthcare.




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