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[Conditions](https://durgical.com/en/conditions/) · [Psychiatry](https://durgical.com/en/conditions/)

# 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

Tap one to see what it is and open it in 3D.

- [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/)
- [Hippocampus](https://durgical.com/en/anatomy/hippocampus/)
- [Amygdala](https://durgical.com/en/anatomy/amygdaloid-body/)
- [Cingulate gyrus](https://durgical.com/en/anatomy/cingulate-gyrus/)
- [Hypothalamus](https://durgical.com/en/anatomy/hypothalamus/)
- [Pituitary gland](https://durgical.com/en/anatomy/pituitary-gland/)
- [Thalamus](https://durgical.com/en/anatomy/thalamus/)
- [Thyroid gland](https://durgical.com/en/anatomy/thyroid-gland/)

## Why it happens

- [The main neurotransmitters](https://durgical.com/en/physiology/the-main-neurotransmitters/)
- [The HPA axis and its circadian rhythm](https://durgical.com/en/physiology/the-hpa-axis-and-its-circadian-rhythm/)
- [Serotonin and melatonin synthesis](https://durgical.com/en/biochemistry/pathways/serotonin-and-melatonin-synthesis/)

## 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](https://durgical.com/en/anatomy/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](https://durgical.com/en/anatomy/amygdaloid-body/) and [hippocampus](https://durgical.com/en/anatomy/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

## Red flags

- Suicidal thoughts with a plan or intent, or a recent suicide attempt
- Psychotic features (delusions of guilt or ruin, hallucinations)
- Refusal to eat or drink, or catatonia
- Postpartum depression with thoughts of harming the baby
- A history of mania or hypomania, which points to bipolar disorder

## 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.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/major-depressive-disorder/)

## Related conditions

- [Suicidal behaviour and suicide risk](https://durgical.com/en/conditions/suicidal-behaviour-and-suicide-risk/)
- [Bipolar disorder](https://durgical.com/en/conditions/bipolar-disorder/)
- [Generalized anxiety disorder](https://durgical.com/en/conditions/generalized-anxiety-disorder/)
- [Alcohol use disorder](https://durgical.com/en/conditions/alcohol-use-disorder/)
- [Hypothyroidism](https://durgical.com/en/conditions/hypothyroidism/)
- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)
- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)

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

Sources: [Depressive disorder (depression)](https://www.who.int/news-room/fact-sheets/detail/depression) (World Health Organization, 2025); [Depression](https://medlineplus.gov/depression.html) (MedlinePlus (National Library of Medicine), 2025).

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Source: https://durgical.com/en/conditions/major-depressive-disorder/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/major-depressive-disorder/