Major depressive disorder !

Major depression is a common illness of persistently low mood or loss of interest that affects sleep, energy and thinking. It is treatable.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A mood disorder defined by at least two weeks of depressed mood or loss of interest or pleasure (anhedonia), with other symptoms that impair daily functioning and are not explained by a substance, another medical condition or a history of mania.

Who gets it

One of the leading causes of disability worldwide; about one adult in twenty is affected at any time, and women about twice as often as men. In Colombia and Latin America it is common and under-treated, often first seen in primary care with physical complaints; Colombia's mental health law (Ley 1616 de 2013) frames access to care.

Causes

Interaction of genetic vulnerability with stressful life events
Dysregulation of monoamine signalling (serotonin, noradrenaline, dopamine) and of the stress-hormone axis
Secondary to medical illness, substances or some drugs (substance- or medication-induced depressive disorder is classified apart)

Risk factors

Personal or family history of depression or suicide
Female sex, the postpartum period and hormonal transitions
Childhood adversity, trauma, violence, loss and poverty
Chronic medical illness (diabetes, heart disease, stroke, chronic pain, hypothyroidism)
Alcohol and other substance use
Social isolation and lack of support

Pathophysiology

No single lesion explains it. Imaging shows altered activity between the prefrontal cortex, anterior cingulate, amygdala and hippocampus, the circuit that regulates emotion. Chronic stress keeps the hypothalamic-pituitary-adrenal axis active, and high cortisol is linked to reduced neuroplasticity and hippocampal volume. Antidepressants act on monoamines, but their delayed effect suggests downstream changes in plasticity.

Classification

Severity: mild, moderate or severe, with or without psychotic features
Single episode or recurrent
Specifier with peripartum onset: onset during pregnancy or within four weeks after delivery
Specifier with seasonal pattern: episodes that recur at a particular time of year, usually autumn or winter
Other specifiers: with melancholic, atypical, catatonic or anxious features

Symptoms and signs

Depressed mood most of the day, nearly every day
Markedly reduced interest or pleasure (anhedonia)
Change in appetite or weight
Insomnia or hypersomnia
Psychomotor slowing or agitation
Fatigue or loss of energy
Feelings of worthlessness or excessive guilt
Poor concentration or indecisiveness
Recurrent thoughts of death or suicide

Diagnosis

Clinical: Clinical interview using DSM-5 or ICD-11 criteria: five or more of nine symptoms for at least two weeks, one being depressed mood or anhedonia. Screening with the PHQ-2 or PHQ-9 (the EPDS in the perinatal period), and a direct, careful assessment of suicide risk in every case.
Tests: No test confirms it. Tests look for medical causes: TSH, complete blood count, glucose, electrolytes, vitamin B12 and folate, and substance screening when relevant.
Imaging: Not routinely needed. Brain imaging is reserved for atypical features, late onset with neurological signs or suspected organic disease.

Differential diagnosis

Bipolar disorder (depressive episode)
Normal grief or adjustment disorder
Persistent depressive disorder (dysthymia)
Hypothyroidism and other medical causes
Substance- or medication-induced depressive disorder
Early dementia in older adults

Goal of treatment

Full remission with recovery of functioning, prevention of relapse and suicide, chosen according to severity and the person's preferences.

Treatment

Conservative: Psychotherapy (cognitive behavioural therapy, interpersonal therapy, behavioural activation) is first-line for mild to moderate depression and is combined with medication in moderate to severe cases.
Medical: Antidepressants: SSRIs are usually first-line; SNRIs, mirtazapine, bupropion, tricyclics and others are alternatives. Effect takes weeks; treatment continues for months after remission to prevent relapse. A boxed warning covers increased suicidal thinking in young people early in treatment.
Procedure: Electroconvulsive therapy (ECT) for severe or treatment-resistant depression, psychotic depression, catatonia, high suicide risk or refusal to eat and drink, and when a rapid response is needed (including in pregnancy).
Follow-up: Nursing priorities: regular suicide-risk assessment, a safe environment, observation for the energy rise in early treatment, adherence, side effects and serotonin syndrome when drugs are combined.
Lifestyle: Regular physical activity, sleep routine, reduced alcohol and social support help as complements to treatment.

Complications

Suicide and self-harm
Chronic or recurrent course
Substance use disorders
Worse outcome of heart disease, diabetes and other chronic illness
Disability, job loss and family difficulties
Impaired mother-infant bonding in peripartum depression

Prognosis

Most people recover from an episode with treatment, but recurrence is frequent and the risk rises with each episode. Early treatment, continuation therapy and follow-up improve the outcome.

Prevention

Screening in primary care and in pregnancy and the postpartum period
Early care after major losses or trauma
Continuation and maintenance treatment in recurrent depression

Test yourself

Think of the answer, then tap the question to see it.

Which two core symptoms must include at least one for a major depressive episode?

Depressed mood or loss of interest or pleasure (anhedonia), with five of nine symptoms lasting at least two weeks.

Which drug class is usually first-line for major depression?

Selective serotonin reuptake inhibitors (SSRIs), alongside psychotherapy when available.

What are two classic indications for electroconvulsive therapy in depression?

Psychotic depression and high suicide risk or refusal to eat and drink; also catatonia and treatment-resistant depression.

What must be ruled out before starting an antidepressant alone?

A history of mania or hypomania (bipolar disorder), because an antidepressant alone may trigger a switch to mania.

What does the peripartum onset specifier require?

Onset of the depressive episode during pregnancy or within four weeks after delivery.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Depressive disorder (depression) (World Health Organization, 2025); Depression (MedlinePlus (National Library of Medicine), 2025).

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Representative model, for educational purposes only.

Frontal lobe highlighted on the Durgical 3D model