Major depressive disorder

Major depressive disorder (MDD), also known as clinical depression, is a mental disorder<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s,<ref name= Spitzer>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after lower back pain.<ref>Template:Cite journal</ref>

The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a mental status examination.<ref name=Pat2015>Template:Cite book</ref> There is no laboratory test for the disorder, but testing may be done to rule out physical conditions that can cause similar symptoms.<ref name=Pat2015/> The most common time of onset is in a person's 20s,Template:Sfn<ref name="Kes2013">Template:Cite journal</ref> with females affected about three times as often as males.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes.

Those with major depressive disorder are typically treated with psychotherapy and antidepressant medication.<ref name="NIH2016" /> While a mainstay of treatment, the clinical efficacy of antidepressants is controversial.<ref name="pmid35918097">Template:Cite journal "Meta-analyses have shown small mean differences between drug and placebo arms, and the clinical significance of these differences continues to be debated."</ref><ref name="s737">Template:Cite journal</ref><ref name="c363">Template:Cite book "The debate around the short‐term efficacy of antidepressants has continued..."</ref><ref name="z830">Template:Cite journal "The efficacy of antidepressants in the acute treatment of patients with moderate-to-severe depression remains a controversial issue."</ref> Hospitalization (which may be involuntary) may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. Electroconvulsive therapy (ECT) may be considered if other measures are not effective.<ref name="NIH2016" />

Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors,<ref name="NIH2016">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> with about 40% of the risk being genetic.Template:Sfn Risk factors include a family history of the condition, major life changes, childhood traumas, environmental lead exposure,<ref>Michael J. McFarland, Aaron Reuben, Matt Hauer. Contribution of Childhood Lead Exposure to Psychopathology in the U.S. Population over the Past 75 Years. Journal of Child Psychology and Psychiatry, 2024 DOI: 10.1111/jcpp.14072</ref> certain medications, chronic health problems, and substance use disorders.<ref name="NIH2016" />Template:Sfn It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health.<ref name="NIH2016" />Template:Sfn Template:TOC limit

Signs and symptoms

File:A woman diagnosed as suffering from melancholia. Colour lith Wellcome L0026686.jpg

An 1892 lithograph of a woman diagnosed with melancholia

A person having a major depressive episode usually exhibits a low mood, which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities.<ref name="g379">Template:Cite book</ref> Depressed people may be preoccupied with or ruminate over thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness or hopelessness.Template:Sfn

Other symptoms of depression include poor concentration and memory,<ref>Template:Cite journal</ref> withdrawal from social situations and activities, reduced sex drive, irritability, and thoughts of death or suicide. Insomnia is common; in the typical pattern, a person wakes very early and cannot get back to sleep. Hypersomnia, or oversleeping, can also happen,Template:Sfn as well as day-night rhythm disturbances, such as diurnal mood variation.<ref>Template:Cite journal</ref> Some antidepressants may also cause insomnia due to their stimulating effect.<ref name="v526">Template:Cite journal</ref> In severe cases, depressed people may have psychotic symptoms. These symptoms include delusions or, less commonly, hallucinations, usually unpleasant.<ref>Template:Harvnb</ref> People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes.<ref>Template:Cite journal</ref>

Template:AnchorA depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization's criteria for depression.<ref>Template:Cite journal</ref> Appetite often decreases, resulting in weight loss, although increased appetite and weight gain occasionally occur.<ref name="b502" />

Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health.<ref name=NIMHPub>Template:Cite book</ref> Family and friends may notice agitation or lethargy.Template:Sfn Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness,<ref>Template:Cite journal</ref> and a more noticeable slowing of movements.<ref>Template:Cite book</ref>

Depressed children may often display an irritable rather than a depressed mood;Template:Sfn most lose interest in school and show a steep decline in academic performance.Template:Sfn Diagnosis may be delayed or missed when symptoms are interpreted as "normal moodiness".<ref name=APA349>Template:Harvnb</ref> Elderly people may not present with classical depressive symptoms.<ref name="SBU" /> Diagnosis and treatment is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other concurrent diseases.<ref name="SBU" />

Cause

File:Diathesis stress model cup analogy.svg

A cup analogy demonstrating the diathesis–stress model that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition<ref>Template:Cite book</ref>

The etiology of depression is not yet fully understood.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref><ref>Template:Cite book</ref> The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression.Template:Sfn<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either genetic,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> American psychiatrist Aaron Beck suggested that a triad of automatic and spontaneous negative thoughts about the self, the world or environment, and the future may lead to other depressive signs and symptoms.<ref name=Beck>Template:Cite book</ref><ref>Template:Cite journal</ref>

Genetics

Genes play a major role in the development of depression.<ref>Template:Cite book</ref> Family and twin studies suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences.<ref name="h988">Template:Cite journal</ref> In 2018, a genome-wide association study discovered 44 genetic variants linked to risk for major depression;<ref>Template:Cite journal</ref> a 2019 study found 102 variants in the genome linked to depression.<ref>Template:Cite journal</ref> However, it appears that major depression is less heritable compared to bipolar disorder and schizophrenia.<ref>Template:Cite book</ref><ref>Template:Cite book</ref> Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings.<ref name="r473">Template:Cite journal</ref> There are also other efforts to examine interactions between life stress and polygenic risk for depression.<ref>Template:Cite journal</ref>

Other health problems

Depression can also arise after a chronic or terminal medical condition, such as HIV/AIDS or asthma, and may be labeled "secondary depression".<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the basal ganglia in Parkinson's disease or immune dysregulation in asthma).<ref>Template:Cite journal</ref> Depression may also be iatrogenic (the result of healthcare), such as drug-induced depression. Therapies associated with depression include interferons, beta blockers,<ref name="e058">Template:Cite journal</ref> isotretinoin,<ref name="w764">Template:Cite journal</ref> contraceptives,<ref name="e058"/> cardiac agents,<ref name="r630">Template:Cite journal</ref> anticonvulsants,<ref name="j396">Template:Cite book</ref> and hormonal agents.<ref name="m323">Template:Cite journal</ref> Celiac disease is another possible contributing factor.<ref name="a192">Template:Cite journal</ref>

Substance use in early age is associated with increased risk of developing depression later in life.<ref>Template:Cite journal</ref> Depression occurring after giving birth is called postpartum depression and is thought to be the result of hormonal changes associated with pregnancy.<ref>Template:Cite journal</ref> Seasonal affective disorder, a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight.<ref name="x376">Template:Cite book</ref> Vitamin B₂, B₆ and B₁₂ deficiency may cause depression in females.<ref>Template:Cite journal</ref>

A 2025 study found that, among more than 172,500 adults in the UK aged 39 and older, those with a history of depression experienced the onset of chronic illnesses approximately 30% earlier than those without depression.<ref>Template:Cite journal</ref>

Environmental

Adverse childhood experiences (incorporating childhood abuse, neglect and family dysfunction) markedly increase the risk of major depression, especially if more than one type.<ref name="e625">Template:Cite book</ref> Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness.<ref name="r126">Template:Cite journal</ref> Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.<ref name="n391">Template:Cite journal</ref> Couples in unhappy marriages have a higher risk of developing clinical depression.<ref>Template:Cite journal Citing among others: Template:Cite journal</ref>

There appears to be a link between air pollution and depression and suicide. There may be an association between long-term PM2.5 exposure and depression, and a possible association between short-term PM10 exposure and suicide.<ref name="pmid31850801">Template:Cite journal</ref>

Living alone has been found to increase the risk of depression by 42%.<ref name="PMH">Template:Cite journal</ref>

Pathophysiology

Template:Further The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits.

Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of tryptophan—a necessary precursor of serotonin and a monoamine—can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression.<ref name="g648">Template:Cite book</ref> Second, the correlation between depression risk and polymorphisms in the 5-HTTLPR gene, which codes for serotonin receptors, suggests a link.<ref name="t044">Template:Cite book</ref> Third, decreased size of the locus coeruleus, reduced activity of tyrosine hydroxylase, increased density of alpha-2 adrenergic receptor, and evidence from rat models suggest decreased adrenergic neurotransmission in depression.<ref>Template:Cite journal</ref> Furthermore, decreased levels of homovanillic acid, altered response to dextroamphetamine, responses of depressive symptoms to dopamine receptor agonists, decreased dopamine receptor D₁ binding in the striatum,<ref>Template:Cite journal</ref> and polymorphism of dopamine receptor genes implicate dopamine, another monoamine, in depression.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Lastly, increased activity of monoamine oxidase, which degrades monoamines, has been associated with depression.<ref>Template:Cite journal</ref> However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway.<ref>Template:Cite book</ref>

One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is a desensitization of self-inhibition in raphe nuclei by the increased serotonin mediated by antidepressants.<ref>Template:Cite journal</ref> However, disinhibition of the dorsal raphe has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular 5-HIAA in people who are depressed that normalized with selective serotonin reuptake inhibitor (SSRI) treatment, and the preference for carbohydrates in people who are depressed.<ref>Template:Cite journal</ref> Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.<ref>Template:Cite journal</ref> A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression.<ref>Template:Cite journal Lay source Medicalxpress</ref>

HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%.<ref>Template:Cite journal</ref> These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed.<ref>Template:Cite journal</ref> Furthermore, a meta-analysis yielded decreased dexamethasone suppression, and increased response to psychological stressors.<ref>Template:Cite journal</ref> Further abnormal results have been obscured with the cortisol awakening response, with increased response being associated with depression.<ref>Template:Cite journal</ref>

There is also a connection between the gut microbiome and the central nervous system, otherwise known as the Gut-Brain axis, which is a two-way communication system between the brain and the gut. Experiments have shown that microbiota in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria Bacteroidetes and Firmicutes were most affected in people with MDD, and they are also impacted in people with irritable bowel syndrome.<ref name="GB">Template:Cite journal</ref> Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected.<ref>Template:Cite journal</ref> There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression.<ref name="GB" />

Theories unifying neuroimaging findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing.<ref>Template:Cite journal</ref> Another model, the cortico-striatal model, suggests that abnormalities of the prefrontal cortex in regulating striatal and subcortical structures result in depression.<ref>Template:Cite journal</ref> Another model proposes hyperactivity of salience structures in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative emotional bias and depression, consistent with emotional bias studies.<ref>Template:Cite journal</ref>

Immune pathogenesis theories on depression

The newer field of psychoneuroimmunology, the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression.

Immune system abnormalities have been observed, including increased levels of cytokines -cells produced by immune cells that affect inflammation- involved in generating sickness behavior, creating a pro-inflammatory profile in MDD.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines.<ref>Template:Cite journal</ref> Research suggests that treatments can reduce pro-inflammatory cell production, like the experimental treatment of ketamine with treatment-resistant depression.<ref>Template:Cite journal</ref> With this, in MDD, people will more likely have a Th-1 dominant immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD.<ref>Template:Cite journal</ref>

Another way cytokines can affect depression is in the kynurenine pathway, and when this is overactivated, it can cause depression. This can be due to too much microglial activation and too little astrocytic activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of COX₂. This, in turn, causes the production of PGE₂, which is a prostaglandin, and this catalyzes the production of indolamine, IDO. IDO causes tryptophan to get converted into kynurenine, and kynurenine becomes quinolinic acid.<ref>Template:Cite journal</ref> Quinolinic acid is an agonist for NMDA receptors, so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms.<ref>Template:Cite journal</ref>

Diagnosis

Assessment

File:A wretched man with an approaching depression; represented b Wellcome V0011145.jpg

Caricature of a man with depression

A diagnostic assessment may be conducted by a suitably trained general practitioner, or by a psychiatrist or psychologist,<ref name=NIMHPub/> who records the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a mental state examination, which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism, self-harm or suicide, and an absence of positive thoughts or plans.<ref name=NIMHPub/> Specialist mental health services are rare in rural areas, and thus diagnosis and management is left largely to primary-care clinicians.<ref>Template:Cite journal</ref> This issue is even more marked in developing countries.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Rating scales are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose;<ref>Template:Cite journal</ref> these include the Hamilton Rating Scale for Depression,<ref>Template:Cite journal</ref> the Beck Depression Inventory<ref>Template:Cite journal</ref> or the Suicide Behaviors Questionnaire-Revised.<ref>Template:Cite journal</ref>

Primary-care physicians have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, physical symptoms often accompany depression. In addition, there may also be barriers related to the person, provider, and/or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases.<ref>Template:Cite journal</ref>

A doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring TSH and thyroxine to exclude hypothyroidism; basic electrolytes and serum calcium to rule out a metabolic disturbance; and a full blood count including ESR to rule out a systemic infection or chronic disease.<ref>Template:Cite journal</ref> Adverse affective reactions to medications or alcohol misuse may be ruled out, as well. Testosterone levels may be evaluated to diagnose hypogonadism, a cause of depression in men.<ref>Template:Cite journal</ref> Vitamin D levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression.<ref name=Parker2017/> Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder, such as Alzheimer's disease.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Cognitive testing and brain imaging can help distinguish depression from dementia.<ref>Template:Cite journal</ref> A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.<ref>Template:Harvnb</ref> No biological tests confirm major depression.<ref>Template:Harvnb</ref> In general, investigations are not repeated for a subsequent episode unless there is a medical indication.

DSM and ICD criteria

The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,<ref>Template:Harvnb</ref> and the authors of both have worked towards conforming one with the other.Template:Sfn Both DSM and ICD mark out typical (main) depressive symptoms.<ref name="DSMvsICD" /> The most recent edition of the DSM is the Fifth Edition, Text Revision (DSM-5-TR),<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and the most recent edition of the ICD is the Eleventh Edition (ICD-11).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Under mood disorders, ICD-11 classifies major depressive disorder as either single episode depressive disorder (where there is no history of depressive episodes, or of mania) or recurrent depressive disorder (where there is a history of prior episodes, with no history of mania).<ref name="ICD11 6A70 and 6A71">ICD-11, 6A70 Single episode depressive disorder and 6A71 Recurrent depressive disorder</ref> ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or anhedonia, accompanied by other symptoms such as "difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue."<ref name="ICD11 6A70 and 6A71"/> These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission).<ref name="ICD11 6A70 and 6A71"/> These two disorders are classified as "Depressive disorders", in the category of "Mood disorders".<ref name="ICD11 6A70 and 6A71"/>

According to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis.<ref>Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Failed verification Major depressive disorder is classified as a mood disorder in the DSM-5.<ref name=Parker2014>Template:Cite journal</ref> The diagnosis hinges on the presence of single or recurrent major depressive episodes.<ref name=APA162>Template:Harvnb</ref> Further qualifiers are used to classify both the episode itself and the course of the disorder. The category Unspecified Depressive Disorder is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode.<ref name=Parker2014/>

Major depressive episode

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks.<ref name="b502">Template:Cite book</ref> Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as psychotic depression—is automatically rated as severe.<ref name=Parker2014/> If the person has had an episode of mania or markedly elevated mood, a diagnosis of bipolar disorder is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".<ref>Template:Harvnb</ref>

Bereavement is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including dysthymia, which involves a chronic but milder mood disturbance;<ref name=Sadock552>Template:Harvnb</ref> recurrent brief depression, consisting of briefer depressive episodes;Template:Sfn<ref>Template:Cite journal</ref> minor depressive disorder, whereby only some symptoms of major depression are present;<ref>Template:Cite journal</ref> and adjustment disorder with depressed mood, which denotes low mood resulting from a psychological response to an identifiable event or stressor.Template:Sfn

Subtypes

The DSM-5 recognizes six further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:

• "Melancholic depression" is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.<ref name="g379"/>
• "Atypical depression" is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.Template:Sfn
• "Catatonic depression" is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia or in manic episodes, or may be caused by neuroleptic malignant syndrome.Template:Sfn
• "Depression with anxious distress" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety.<ref name="t660">Template:Cite journal</ref>
• "Depression with peri-partum onset" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification "postpartum depression", but this was changed to not exclude cases of depressed woman during pregnancy. Depression with peripartum onset has an incidence rate of 3–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery.Template:Sfn
• "Seasonal affective disorder" (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.Template:Sfn

Differential diagnoses

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}}

To confirm major depressive disorder as the most likely diagnosis, other potential diagnoses must be considered, including dysthymia, adjustment disorder with depressed mood, or bipolar disorder. Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as double depression).<ref name=Sadock552/> Adjustment disorder with depressed mood is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode.Template:Sfn

Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications, and substance use disorders. Depression due to physical illness is diagnosed as a mood disorder due to a general medical condition. This condition is determined based on history, laboratory findings, or physical examination. When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a toxin, it is then diagnosed as a specific mood disorder (previously called substance-induced mood disorder).Template:Sfn

Screening and prevention

Preventive efforts may result in decreases in rates of the condition of between 22 and 38%.<ref name=Cuijpers2008 /> Since 2016, the United States Preventive Services Task Force (USPSTF) has recommended screening for depression among those over the age 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed;<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="DD">Template:Cite journal</ref> though a 2005 Cochrane review found that the routine use of screening questionnaires has little effect on detection or treatment.<ref name=Gil2005>Template:Cite journal</ref> Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data.<ref>Template:Cite journal</ref><ref name="DD" />

Behavioral interventions, such as interpersonal therapy and cognitive-behavioral therapy, are effective at preventing new onset depression.<ref name=Cuijpers2008>Template:Cite journal</ref><ref name=Munoz2012>Template:Cite journal</ref><ref name=Cuijpers2012>Template:Cite conference</ref> Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet.<ref>Template:Cite journal</ref>

The Netherlands mental health care system provides preventive interventions, such as the "Coping with Depression" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.<ref name=Munoz2012 /><ref name=Cuijpers2009>Template:Cite journal</ref>

Management

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} The most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is resistant to treatment.<ref name= Karrouri2021>Template:Cite journal</ref> American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, co-existing disorders, prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT, transcranial magnetic stimulation (TMS) or light therapy. Antidepressant medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and should be given to all people with severe depression unless ECT is planned.<ref name=apaguidelines>Template:Cite journal; Third edition {{#invoke:doi|main}}</ref> There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care.<ref>Template:Cite journal</ref>

Psychotherapy is the treatment of choice (over medication) for people under 18,<ref name=NICE2004>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and cognitive behavioral therapy (CBT), third wave CBT and interpersonal therapy may help prevent depression.<ref>Template:Cite journal</ref> The UK National Institute for Health and Care Excellence (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the risk-benefit ratio is poor. The guidelines recommend that antidepressants treatment in combination with psychosocial interventions should be considered for:<ref name= NICE2004/>

• People with a history of moderate or severe depression
• Those with mild depression that has been present for a long period
• As a second line treatment for mild depression that persists after other interventions
• As a first line treatment for moderate or severe depression.

The guidelines further note that antidepressant treatment should be continued for at least six months to reduce the risk of relapse, and that SSRIs are better tolerated than tricyclic antidepressants.<ref name="o804">Template:Cite book</ref>Template:Rp

Treatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition.<ref>Template:Cite journal</ref> There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children.<ref>Template:Cite journal</ref>

Lifestyle

File:Soccer football informal in Manipur India cropped.jpg

Physical exercise is one recommended way to manage mild depression.

Physical exercise has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment.<ref>Template:Cite journal</ref><ref name="m647">Template:Cite journal</ref> It is equivalent to the use of medications or psychological therapies in most people.<ref name="Coo2013" /> In older people it does appear to decrease depression.<ref name="y793">Template:Cite journal</ref> Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods.<ref name="z728">Template:Cite journal</ref> In studies, smoking cessation has benefits in depression.<ref name="d893">Template:Cite journal</ref>

Talking therapies

Template:See also Talking therapy (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical social workers, counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not other treatments.<ref>Template:Cite journal</ref> With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.<ref>Template:Cite journal</ref><ref>Template:Cite encyclopedia</ref> There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of treatment-resistant depression in the short term.<ref>Template:Cite journal</ref> Psychotherapy has been shown to be effective in older people.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions.

The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression.<ref>Template:Cite journal</ref> CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression.<ref name=abct>Childhood Depression. abct.org. Last updated: 30 July 2010</ref> In people under 18, according to the National Institute for Health and Clinical Excellence, medication should be offered only in conjunction with a psychological therapy, such as CBT, interpersonal therapy, or family therapy.<ref name=NICEkids5>Template:Cite book</ref> Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer cognitive distortions.<ref>Template:Cite journal</ref> CBT is particularly beneficial in preventing relapse.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression.<ref name=Nieuwenhuijsen2020/> Several variants of cognitive behavior therapy have been used in those with depression, the most notable being rational emotive behavior therapy,<ref name="h303">Template:Cite journal</ref> and mindfulness-based cognitive therapy.<ref name="g399">Template:Cite book</ref> Mindfulness-based stress reduction programs may reduce depression symptoms.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Mindfulness programs also appear to be a promising intervention in youth.<ref>Template:Cite journal</ref> Problem solving therapy, cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly.<ref name="Alexopoulos2019" />

Psychoanalysis is a school of thought, founded by Sigmund Freud, which emphasizes the resolution of unconscious mental conflicts.<ref>Template:Cite book</ref> Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression.<ref name="o365">Template:Cite book</ref> A more widely practiced therapy, called psychodynamic psychotherapy, is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus.<ref name="o365">Template:Cite book</ref> In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression.<ref>Template:Cite journal</ref>

Antidepressants

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Sertraline (Zoloft) is used primarily to treat major depression in adults.

Conflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression.<ref>Template:Cite journal</ref> A review commissioned by the National Institute for Health and Care Excellence (UK) concluded that there is strong evidence that SSRIs, such as escitalopram, paroxetine, and sertraline, have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.<ref name="Depression in Adults">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Similarly, a Cochrane systematic review of clinical trials of the generic tricyclic antidepressant amitriptyline concluded that there is strong evidence that its efficacy is superior to placebo.<ref>Template:Cite journal</ref> Antidepressants work less well for the elderly than for younger individuals with depression.<ref name="Alexopoulos2019">Template:Cite journal</ref>

To find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50 to 75%, and it can take at least six to eight weeks from the start of medication to improvement.<ref name="apaguidelines" /><ref>Template:Cite journal</ref> Antidepressant medication treatment is usually continued for 6–9 months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended.<ref name="o804" />Template:Rp

SSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and safety.<ref name="j508">Template:Cite book</ref> People who do not respond to one SSRI can be switched to another antidepressant, and this results in improvement in almost 50% of cases.<ref>Template:Cite journal</ref> Another option is to augment the atypical antidepressant bupropion to the SSRI as an adjunctive treatment.<ref name="f609">Template:Cite journal</ref> Venlafaxine, an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs.<ref name="r829">Template:Cite book</ref> However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts.<ref name="NIHR-2022">Template:Cite journal</ref><ref name="Zhou-2020">Template:Cite journal</ref><ref name="Hetrick-2021">Template:Cite journal</ref><ref name="Solmi-2020">Template:Cite journal</ref><ref name="Boaden-2020">Template:Cite journal</ref><ref name="Correll-2021">Template:Cite journal</ref><ref>Template:Cite journal</ref>

For children and adolescents with moderate-to-severe depressive disorder, fluoxetine seems to be the best treatment (either with or without cognitive behavioural therapy) but more research is needed to be certain.<ref name="NIHR-2020">Template:Cite journal</ref><ref name="Zhou-2020" /><ref>Template:Cite journal</ref><ref name="Hetrick-2021" /> Sertraline, escitalopram, duloxetine might also help in reducing symptoms.<ref name="r716">Template:Cite book</ref> Some antidepressants have not been shown to be effective.<ref name="v001">Template:Cite book</ref><ref name="Zhou-2020" /> Medications are not recommended in children with mild disease.<ref name="r716"/>

There is also insufficient evidence to determine effectiveness in those with depression complicated by dementia.<ref name="f390">Template:Cite journal</ref> Any antidepressant can cause low blood sodium levels;<ref name="g496">Template:Cite journal</ref> nevertheless, it has been reported more often with SSRIs.<ref name="j072">Template:Cite book</ref> It is not uncommon for SSRIs to cause or worsen insomnia; the sedating atypical antidepressant mirtazapine can be used in such cases.<ref>Template:Cite journal</ref><ref name="j072"/>

Irreversible monoamine oxidase inhibitors, an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed.<ref>Template:Cite journal</ref> The safety profile is different with reversible monoamine oxidase inhibitors, such as moclobemide, where the risk of serious dietary interactions is negligible and dietary restrictions are less strict.<ref>Template:Cite journal</ref>

It is unclear whether antidepressants affect a person's risk of suicide.<ref>Template:Cite journal</ref> For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both suicidal ideations and suicidal behavior in those treated with SSRIs.<ref name=FDA>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection;<ref>Template:Cite journal</ref> another an increased risk;<ref>Template:Cite journal</ref> and a third no risk in those 25–65 years old and a decreased risk in those more than 65.<ref>Template:Cite journal</ref> A black box warning was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years old.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.<ref>Template:Cite report</ref>

Other medications and supplements

The combined use of antidepressants plus benzodiazepines demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate.<ref name=Ogawa2019>Template:Cite journal</ref>

For treatment-resistant depression, adding on the atypical antipsychotic brexpiprazole for short-term or acute management may be considered.<ref name=Ralovska2023>Template:Cite journal</ref> Brexpiprazole may be effective for some people, however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and akathisia.<ref name=Ralovska2023/> Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this adjunctive therapy for longer term management is not clear.<ref name=Ralovska2023/>

Ketamine may have a rapid antidepressant effect lasting less than two weeks; there is limited evidence of any effect after that, common acute side effects, and longer-term studies of safety and adverse effects are needed.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> A nasal spray form of esketamine was approved by the FDA in March 2019 for use in treatment-resistant depression when combined with an oral antidepressant; risk of substance use disorder and concerns about its safety, serious adverse effects, tolerability, effect on suicidality, lack of information about dosage, whether the studies on it adequately represent broad populations, and escalating use of the product have been raised by an international panel of experts.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance, celecoxib, an NSAID, is a selective COX-2 inhibitor– which is an enzyme that helps in the production of pain and inflammation.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling.<ref name="pmid37240605">Template:Cite journal</ref><ref>Template:Cite journal</ref>

Statins, which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too.<ref>Template:Cite journal</ref>

There is insufficient high quality evidence to suggest omega-3 fatty acids are effective in depression.<ref>Template:Cite journal</ref> There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient.<ref name=Parker2017>Template:Cite journal</ref> Lithium appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%.<ref name="b789">Template:Cite journal</ref> There is a narrow range of effective and safe dosages of lithium thus close monitoring may be needed.<ref name="x631">Template:Cite journal</ref> Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms.<ref name="z385">Template:Cite journal</ref> Limited evidence suggests stimulants, such as amphetamine and modafinil, may be effective in the short term, or as adjuvant therapy.<ref name="j433">Template:Cite journal</ref><ref>Template:Cite journal</ref> Also, it is suggested that folate supplements may have a role in depression management.<ref>Template:Cite journal</ref> There is tentative evidence for benefit from testosterone in males.<ref>Template:Cite journal</ref>

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in a person with depression to provide relief from psychiatric illnesses.<ref name="d505">Template:Cite journal</ref> ECT is used with informed consent<ref name="u822">Template:Cite journal</ref> as a last line of intervention for major depressive disorder.<ref name="o804" /> A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar.<ref>Template:Cite journal</ref> Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.<ref>Template:Cite journal</ref> Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anesthesia.<ref name="SG">Surgeon General (1999). Mental Health: A Report of the Surgeon General Template:Webarchive, chapter 4.</ref>Template:Rp Immediately following treatment, the most common adverse effects are confusion and memory loss.<ref name=FDA2011rev>FDA. FDA Executive Summary Template:Webarchive. Prepared for the 27–28 January 2011 meeting of the Neurological Devices Panel Meeting to Discuss the Classification of Electroconvulsive Therapy Devices (ECT). Quote, p38: "Three major practice guidelines have been published on ECT. These guidelines include: APA Task Force on ECT (2001); Third report of the Royal College of Psychiatrists' Special Committee on ECT (2004); National Institute for Health and Clinical Excellence (NICE 2003; NICE 2009). There is significant agreement between the three sets of recommendations."</ref><ref>Template:Cite book</ref> ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.<ref name=Pompili2014Rev>Template:Cite journal</ref>

A usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments.<ref name="d426">Template:Cite book</ref> ECT is administered under anesthesia with a muscle relaxant.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT.<ref name=FDA2011rev />

ECT appears to work in the short term via an anticonvulsant effect mostly in the frontal lobes, and longer term via neurotrophic effects primarily in the medial temporal lobe.<ref name=Abbott2014>Template:Cite journal</ref>

Other

Transcranial magnetic stimulation (TMS) or deep transcranial magnetic stimulation is a noninvasive method used to stimulate small regions of the brain.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008.<ref name="g379" /> Recent systematic reviews have found that the effects of TMS on clinical response, remission, and severity in depression appear not to be statistically or clinically significant.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> The American Psychiatric Association,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> the Canadian Network for Mood and Anxiety Disorders,<ref>Template:Cite journal</ref> and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD.<ref>Template:Cite journal</ref> Transcranial direct current stimulation (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

There is a small amount of evidence that sleep deprivation may improve depressive symptoms in some individuals,<ref>Template:Cite journal</ref> with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of mania or hypomania.<ref>Template:Cite journal</ref> There is insufficient evidence for Reiki<ref>Template:Cite journal</ref> and dance movement therapy in depression.<ref>Template:Cite journal</ref> Cannabis is specifically not recommended as a treatment.<ref>Template:Cite journal</ref>

The microbiome of people with major depressive disorder differs from that of healthy people, and probiotic and synbiotic treatment may achieve a modest depressive symptom reduction.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> With this, fecal microbiota transplants (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant.<ref>Template:Cite journal</ref>

Prognosis

Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life,<ref>Template:Cite journal</ref> with a lifetime average of four episodes.<ref>Template:Cite journal</ref> Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence.<ref>Template:Cite journal</ref> Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and family dysfunction.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

A high proportion of people who experience full symptomatic remission still have at least one not fully resolved symptom after treatment.<ref name=Culpepper2015>Template:Cite journal</ref> Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment.<ref name=Culpepper2015/> Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many randomized controlled trials indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use.<ref>Template:Cite journal</ref>

Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder.<ref>Template:Cite journal</ref> The median duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.<ref>Template:Cite journal</ref> According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months.<ref>Template:Cite journal</ref>

Ability to work

Depression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year.<ref name=Nieuwenhuijsen2020>Template:Cite journal</ref> Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as online cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave.<ref name=Nieuwenhuijsen2020/>

Life expectancy and the risk of suicide

Depressed individuals have a shorter life expectancy than those without depression, in part because people who are depressed are at risk of dying of suicide.<ref>Template:Cite journal</ref> About 50% of people who die of suicide have a mood disorder such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and borderline personality disorder.Template:Sfn<ref>Template:Cite journal</ref> About 2–8% of adults with major depression die by suicide.<ref name="z273">Template:Cite journal</ref><ref>Template:Cite book</ref> In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women,<ref>Template:Cite journal</ref> even though suicide attempts are more frequent in women.<ref>Template:Cite journal</ref>

Depressed people also have a higher rate of dying from other causes.<ref>Template:Cite journal</ref> There is a 1.5- to 2-fold increased risk of cardiovascular disease, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications.<ref>Template:Cite journal</ref> Cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.<ref>Template:Cite journal</ref>

Epidemiology

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File:Unipolar depressive disorders world map - DALY - WHO2004.svg

CitationClass=web }}</ref> Template:Div col Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Legend Template:Div col end

Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population).<ref name="GBD 2017 prevalence">Template:Cite journal</ref> The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8–18% range. Lifetime rates are higher in the developed world (15%) compared to the developing world (11%).<ref name="Kes2013" />

In the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%).<ref name= NIMHMajorDepression>{{#invoke:citation/CS1|citation |CitationClass=web }} Template:Pd-notice</ref> 15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers.<ref name="DP">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Among individuals reporting two or more races, the US prevalence is highest.<ref name=NIMHMajorDepression/> Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder.<ref name="DP" />

Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this.<ref name="Kuehner03">Template:Cite journal</ref> The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors.<ref name="Kuehner03" /> In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the Global Burden of Disease Study as the fifth most common cause of years lived with disability and the 18th most common for disability-adjusted life years.<ref>Template:Citation</ref>

People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60.<ref>Template:Cite journal</ref> The risk of major depression is increased with neurological conditions such as stroke, Parkinson's disease, or multiple sclerosis, and during the first year after childbirth (Postpartum depression).<ref>Template:Cite journal</ref> It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac disease outcome than to a better one.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, e.g., homelessness.<ref>Gelder, M, Mayou, R and Geddes, J (2005). Psychiatry. 3rd ed. New York: Oxford. p. 105.</ref> Depression is common among those over 65 years of age and increases in frequency beyond this age.<ref name="SBU">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The risk of depression increases in relation to the frailty of the individual.<ref>Template:Cite journal</ref> Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly.<ref name="SBU" /> Both symptoms and treatment among the elderly differ from those of the rest of the population.<ref name="SBU" />

Major depression was the leading cause of disease burden in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after HIV, according to the WHO.<ref>Template:Cite journal</ref> Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.<ref>Template:Cite journal</ref>

Comorbidity

Major depression frequently co-occurs with other psychiatric problems. The 1990–92 National Comorbidity Survey (US) reported that half of those with major depression also have lifetime anxiety and its associated disorders, such as generalized anxiety disorder.<ref>Template:Cite journal</ref> Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior.<ref>Template:Cite journal</ref> Depressed people have increased rates of alcohol and substance use, particularly dependence,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and around a third of individuals diagnosed with attention deficit hyperactivity disorder (ADHD) develop comorbid depression.<ref>Template:Cite book</ref> Post-traumatic stress disorder and depression often co-occur.<ref name=NIMHPub/> Depression may also coexist with ADHD, complicating the diagnosis and treatment of both.<ref>Template:Cite journal</ref> Depression is also frequently comorbid with alcohol use disorder and personality disorders.<ref>Template:Cite journal</ref> Depression can also be exacerbated during particular months (usually winter) in those with seasonal affective disorder. While overuse of digital media has been associated with depressive symptoms, using digital media may also improve mood in some situations.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Depression and pain often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5 to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain.<ref>Template:Cite journal</ref> Depression often coexists with physical disorders common among the elderly, such as stroke, other cardiovascular diseases,<ref>Template:Cite journal</ref> Parkinson's disease, and chronic obstructive pulmonary disease.<ref>Template:Cite journal</ref>

History

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The Ancient Greek physician Hippocrates described a syndrome of melancholia ({{#invoke:Lang|lang}}, Template:Transliteration) as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment.<ref>Hippocrates, Aphorisms, Section 6.23</ref> It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included.<ref name= Radden2003>Template:Cite journal</ref>

File:Hippocrates pushkin02.jpg

Diagnoses of depression go back at least as far as Hippocrates.

The term depression itself was derived from the Latin verb {{#invoke:Lang|lang}}, meaning "to press down".<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Baker's Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson in a similar sense in 1753.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The term also came into use in physiology and economics. An early usage referring to a psychiatric symptom was by French psychiatrist Louis Delasiauve in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function.<ref>Template:Cite journal</ref> Since Aristotle, melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women.<ref name=Radden2003/>

Although melancholia remained the dominant diagnostic term, depression gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist Emil Kraepelin may have been the first to use it as the overarching term, referring to different kinds of melancholia as depressive states.<ref name="Davison2006">Template:Cite journal</ref> Freud likened the state of melancholia to mourning in his 1917 paper Mourning and Melancholia. He theorized that objective loss, such as the loss of a valued relationship through death or a romantic break-up, results in subjective loss as well; the depressed individual has identified with the object of affection through an unconscious, narcissistic process called the libidinal cathexis of the ego. Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised.<ref>Template:Cite journal</ref> The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness.<ref>Template:Cite book</ref> He also emphasized early life experiences as a predisposing factor.<ref name=Radden2003/> Adolf Meyer put forward a mixed social and biological framework emphasizing reactions in the context of an individual's life, and argued that the term depression should be used instead of melancholia.<ref name="Lewis1934">Template:Cite journal</ref> The first version of the DSM (DSM-I, 1952) contained depressive reaction and the DSM-II (1968) depressive neurosis, defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders.<ref name="DSMII">Template:Cite book</ref>

The term unipolar (along with the related term bipolar) was coined by the neurologist and psychiatrist Karl Kleist, and subsequently used by his disciples Edda Neele and Karl Leonhard.<ref>Angst J. Terminology, history and definition of bipolar spectrum. In: Maj M, Akiskal HS, López-Ibor JJ, Sartorius N (eds.), Bipolar disorders. Chichester: Wiley & Sons, LTD; 2002. pp. 53–55.</ref>

The term major depressive disorder was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the "Research Diagnostic Criteria", building on earlier Feighner Criteria),<ref name= Spitzer/> and was incorporated into the DSM-III in 1980.<ref name="Philipp1991">Template:Cite journal</ref> The American Psychiatric Association added "major depressive disorder" to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III),<ref name=Her2008/> as a split of the previous depressive neurosis in the DSM-II, which also encompassed the conditions now known as dysthymia and adjustment disorder with depressed mood.<ref name=Her2008>Template:Cite book</ref> To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a mild depressive episode, adding higher threshold categories for moderate and severe episodes.<ref name="DSMvsICD">Template:Cite book</ref><ref name="Philipp1991" /> The ancient idea of melancholia still survives in the notion of a melancholic subtype.

The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia.<ref name="ActaPsychiatrica06">Template:Cite journal</ref><ref>Template:Cite journal</ref> There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s.<ref>Template:Cite book</ref>

Society and culture

Terminology

File:Abraham Lincoln O-60 by Brady, 1862.jpg

The 16th American president, Abraham Lincoln, had "melancholy", a condition that now may be referred to as clinical depression.<ref>Wolf, Joshua "Lincoln's Great Depression" Template:Webarchive, The Atlantic, October 2005. Retrieved 10 October 2009</ref>

The term depression is used in a number of different ways. It is often used to mean this syndrome but may refer to other mood disorders or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. "Because of the lack of scientific certainty," one commentator has observed, "the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it."<ref>Template:Cite journal</ref> There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Cultural dimension

Cultural differences contribute to different prevalence of symptoms. "Do the Chinese somatize depression? A cross-cultural study" by Parker et al. discusses the cultural differences in prevalent symptoms of depression between individualistic and collectivistic cultures. The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less affective symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures 'warranting' or validating one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values.<ref>Template:Cite journal</ref>

Stigma

Historical figures were often reluctant to discuss or seek treatment for depression due to social stigma about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author Mary Shelley,<ref>Template:Cite book</ref> American-British writer Henry James,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and American president Abraham Lincoln.<ref>Template:Cite book</ref> Some well-known contemporary people with possible depression include Canadian songwriter Leonard Cohen<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and American playwright and novelist Tennessee Williams.<ref>Template:Cite journal</ref> Some pioneering psychologists, such as Americans William James<ref>Template:Cite book</ref><ref name="HistoryJames">Template:Harvnb</ref> and John B. Watson,<ref>Template:Cite book</ref> dealt with their own depression.

File:Norges statsminister Kjell Magne Bondevik.jpg

In 1998, the Norwegian PM Kjell Magne Bondevik publicly announced he would take a leave of absence in order to recover from a depressive episode.

There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to Aristotelian times.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> British literature gives many examples of reflections on depression.<ref>Template:Cite book</ref> English philosopher John Stuart Mill experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet Samuel Taylor Coleridge's "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear."<ref>Template:Cite book</ref><ref>Template:Cite journal</ref> English writer Samuel Johnson used the term "the black dog" in the 1780s to describe his own depression,<ref name=McKinlay05>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=HistoryCollection>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and it was subsequently popularized by British Prime Minister Sir Winston Churchill, who also had the disorder.<ref name=McKinlay05 /><ref name=HistoryCollection /> Johann Wolfgang von Goethe in his Faust, Part One, published in 1808, has Mephistopheles assume the form of a black dog, specifically a poodle.

Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref> In the UK, the Royal College of Psychiatrists and the Royal College of General Practitioners conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996;<ref>Template:Cite journal</ref> a MORI study conducted afterwards showed a small positive change in public attitudes to depression and treatment.<ref>Template:Cite journal</ref>

While serving his first term as Prime Minister of Norway, Kjell Magne Bondevik attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest ranking world leader to admit to suffering from a mental illness while in office. Upon this revelation, Anne Enger became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable.<ref name=Jones2011Fighting>Template:Cite journal</ref><ref>BBC Newsnight, 21 January 2008.</ref>

References

Cited works

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