Major Depressive disorder (MDD)

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What is Major Depressive Disorder (MDD)?

Major depressive disorder is common and disabling[1][2]

MDD (also known as major depressive disorder) is characterised by prolonged and clinically significant symptoms of depression that are not clearly caused by another medical condition.[3] With a lifetime prevalence of 3–21%,[1][4][5] the various sub-types of MDD are associated with significant morbidity, disability and mortality,[1][2][6] including an increased risk of suicide.[7] The wider societal impact of MDD is also considerable,[8] with a reduced ability to work and be productive.[9] Therapeutic approaches include pharmacological and non-pharmacological treatments, although up to 3 in 10 patients fail to respond to treatment and are considered treatment resistant (fail to respond to two or more antidepressants during a single episode of major depression).[10]

The prevelance of MDD is 10-20%

According to WHO 2015 estimates, over 40 million people suffer with depression in Europe.[11]

A 2020 systematic review on the prevalence of MDD revealed a lifetime prevalence among adults of between 3-21% in Europe.[1][4] This included data from 38 surveys conducted in 29 countries worldwide and showed that Europe had the highest regional average lifetime and 12-month prevalence (11.32% and 5.2%, respectively).[1]

Lifetime prevalence of MDD in Europe[1][4]

Country
Lifetime Prevalence (%)
Country

Belgium

Lifetime Prevalence (%)

14.1 ± 1.0

Country

France

Lifetime Prevalence (%)

21.0 ± 1.1

Country

Germany

Lifetime Prevalence (%)

9.9 ± 0.6

Country

Italy

Lifetime Prevalence (%)

9.9 ± 0.5

Country

Netherlands

Lifetime Prevalence (%)

17.9 ± 1.0

Country

Spain

Lifetime Prevalence (%)

10.6 ± 0.6

Symptoms of MDD

The symptoms of major depression impair an individual's ability to perform normal daily functions at home and at work.[3] Symptoms include:

Sustained low mood[3]
Loss of interest or pleasure in activities[3]
Fatigue[3]
Sleep disturbance[3]
Impaired concentration or executive function[3]
Change in eating patterns[3]
Feelings of worthlessness or guilt[3]

A large cross-sectional study involving 2,811 adult patients experiencing a major depressive episode established the following symptom frequency;[12]

Irritable mood
Emotional/changeable mood
Distractibility
Psychomotor agitation
Impulsivity
Aggression
Racing thoughts
Pressure to keep talking

Plus, suicide risk is significantly elevated among patients with major depression.[3]

A survey conducted in Italy on 324 patients with major depression and their relatives found:[8]

Reported a reduction in social activities
Reported a reduction in leisure activities
Expressed concerns about the future

Note: these data refer to a mixed population of both patients and carers – separate data for each group was not made available

To learn more about the impact MDD can have on patients and those around them, visit the 'Quality of Life' page

Classification of MDD

Depressive disorders are classified according to the 2013 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)[3] or the International Classification of Diseases, 10th Revision (ICD-10) classification of mental and behavioural disorders.[13] An update to the ICD has been developed (ICD-11), but global uptake and implementation is still underway.[14]

Prognosis of MDD

MDD often follows a chronic course, first conceptualised in 1991 by the MacArthur Foundation Research Network on the Psychobiology of Depression task force.[15] On average, a patient faces just under 4 lifetime episodes, with the longest episode lasting 26 weeks.[16]

MDD relapse and recurrence[17][18][19]

Consensus definitions of key stages and outcomes in MDD were developed, and revised in 2006,[15][20] with more recent evidence-based modifications published in 2019[21]

Key stage
Definition
Timeframe
Key stage

MDD episode

Definition

Symptoms meet DSM-5 / ICD-10 criteria

Timeframe

≥ 2 weeks

Key stage
MDD episode remission
Definition
A less symptomatic state
HAMD-17 ≤ 4
Timeframe
Key stage
MDD recurrence
Definition

A new period of MDD symptoms
separated from a previous episode

Timeframe

Causes of MDD

MDD is a complex disorder that results from a combination of several genetic factors and environmental influences.[22] Studies have identified the following factors to be associated with MDD, which include but are not limited to:[1][5][16][22][23][24][25]

Female gender[1][5][16][23][24]
Being divorced or separated[1][16]
Physical or mental abuse during childhood[1][25]
Unemployment[1]
Family history of depression (first-degree relative)[22]

The COVID-19 pandemic has caused a decline in mental wellbeing among all age groups in Europe, especially among those who have lost their jobs.[26]

Risk of depression by age group and e-survey round, EU27 (%)[26]

Note: Based on WHO-5 mental well-being index. People with a WHO-5 score of 50 or lower are considered to be at risk of depression
Chart adapted from Eurofound[26]

To learn more about the causes of depression visit the ‘Causes of MDD' page

Impact of MDD

WHO reports that mental health is a leading cause of disability worldwide.[27]

Compared to the general population, patients with MDD have significantly greater rates of:[28]

Absenteeism[28]
Total work impairment[28]
Overall activity impairment[28]
Healthcare utilisation[28]

Comorbidities and MDD

Studies have consistently shown a strong correlation between physical comorbidities and MDD.[1][29]


The World Health survey found between 9-23% of participants across 60 countries with one or more chronic physical disease had comorbid depression.[30]

The World Health survey found there was a significant association between depression and:[30]

Angina
Arthritis
Asthma
Diabetes

Plus, patients with depression are more than 1.5 times likely to develop ischaemic heart disease than the general population.[31]

Subtypes of major depression/MDD

Subtypes of MDD include postpartum and antepartum depression, psychotic depression and seasonal affective disorder.[3]

Patients with other mental health conditions may also experience depressive symptoms but do not necessarily fall within the classification of major depression. For example, patients with bipolar disorder will present with symptoms of depression, but they are differentiated from MDD due to the presence of manic, hypomanic, or mixed episodes[13]

Postpartum / antepartum depression begins during pregnancy or within 4 weeks of delivery.[3] Symptoms include severe psychotic episodes characterised by mood changes, hallucinations and thoughts of infanticide.[3]

In a systematic literature review, more than 1 in 10 previously healthy mothers with no prior history of depression demonstrated symptoms of postpartum depression.[32] Although less common, men can also suffer from postpartum depression.


Although a number of groups worldwide have determined elevated levels of anxiety and depression among pregnant women during the COVID-19 pandemic,[33][34] a cohort study of women giving birth in Israel during the pandemic showed no evidence of an increased risk of MDD.[35]

Some risk factors for postpartum depression can include:[36]
A history of violence and abuse
High number of prior pregnancies
Gestational diabetes
Excessive weight
Caesarean section
Sleep disturbance
History of depression
Lack of social support
The ICD-10 classification of psychotic depression [category F32.3] requires the presence of hallucinations, delusions, psychomotor retardation, or stupor so severe that ordinary social activities are impossible.[13]

A 2018 systematic review and meta-analysis reported a lifetime prevalence of 0.35–1%, with a similar gender distribution as MDD.[37] Patients often present with more severe illness and have a longer duration of hospitalisation compared to non-psychotic depressive patients.[38] Limited research into risk factors has identified a family history of psychosis and bipolar disorder.[37][38]

SAD is characterised by temporary symptomatology that follows distinct seasonal patterns, where symptoms tend to resolve when the season changes.[3][39]

SAD usually occurs during months with low sunlight and patients report:

Increased sleep duration[39]
Feelings of worthlessness[39]
Increased appetite/weight gain[39]
Difficulty concentrating[39]
Fatigue/loss of energy[39]
Suicidal thoughts[39]

To learn more about the symptoms of depression and how to diagnose MDD, visit the ‘Diagnosis and Symptoms’ page.

Abbreviations

ACNP, American College of Neuropsychiatry. DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. ED, Emergency department. ER, Emergency room. HAMD-17, Hamilton Depression Rating Scale. ICD-10, International Classification for Diseases, 10th Revision. MDD, Major depressive disorder. SAD, Seasonal affective disorder.