Worldwide, depression is a seriously disabling public health problem of very high prevalence.1
Major depressive disorder has a 12-month prevalence of 6·6% and a lifetime prevalence of 16·2%, is twice as common in women as in men, and causes considerable impairment. Age-of-onset distributions suggest that depression is prevalent for the entire lifespan.2
The disorder not only produces decrements in health that are equivalent to those of other chronic diseases (eg, angina, arthritis, asthma, and diabetes), but also worsens mean health scores substantially more when comorbid with these diseases, than when the diseases occur alone.3
A crucial implication is that primary care providers should not ignore the presence of depression when patients have a chronic physical disorder.
Overdetection and underdetection are important factors that should be considered to ensure the appropriate diagnosis and management of clinical depression.4
Although a meta-analysis5
concluded that general practitioners correctly exclude depression in most individuals who are not depressed, overdetections (false positives) can outnumber missed cases. The presence of anxiety with depression can increase difficulties in diagnosis. Some researchers have argued that the establishment of anxious depression as a specific diagnosis would substantially improve identification of depression in primary care settings, and such a category has been proposed for the fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) and for the 11th revision of the international classification of diseases (ICD-11).6
Although in this Seminar we focus on major depressive disorder (bipolar disorder has been addressed in other Seminars in The Lancet7
), studies that better elucidate the boundaries and phenotypical description of the disorder are highly relevant. In up to 40% of patients, major depression is associated with lifetime occurrences of isolated manic or hypomanic symptoms that do not cluster in a way that is consistent with a diagnosis of hypomania. Furthermore, such symptoms can be concurrent with syndromal-level major depressive disorder.8,9
Further investigation is needed to examine the treatment and prognosis of major depression that is associated either concurrently, or at other points in the patient’s history, with hypomanic symptoms.10
This investigation could be facilitated by proposed changes in DSM-5, which include the possibility of a mixed specifier indicating the presence of sub-threshold hypomanic symptoms in those with unipolar disorder.
Major depressive disorder was assumed to precede generalised anxiety disorder until a 32-year prospective follow-up study11
challenged this notion. Indeed, the reverse pattern seems to be frequently present, and the combination of generalised anxiety disorder and major depression might represent an additional burden. Social anxiety disorder (social phobia) is now also regarded as an important and consistent risk factor for the development of severe depression.12
Furthermore, comorbid personality disorder seems to confer a worse prognosis and poorer treatment response than does major depression alone.13
Some of the risk factors for the metabolic syndrome (eg, obesity), might also increase the risk of depression and, in turn, depression increases the risk for development of obesity.14
These two-way relations might be the reason for the increased association between depression and coronary artery disease.
Kendler and colleagues15
have shown a major relation between depression and coronary artery disease, mainly in acute states. A high severity of depression within several weeks of admission to hospital for an acute coronary syndrome, or an inadequate treatment response in depression, can double cardiac mortality in 6·7 years of follow-up.16
Studies examining depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease have shown a high likelihood of major adverse cardiac events in those with depression.17
These results have led to the recommendation that all patients with coronary artery disease be screened for depression;18
however, this recommendation is somewhat controversial.19
Studies of the relation between depression and diabetes have led to new conclusions—eg, that clinical depression is associated with a 65% increased risk of diabetes in elderly people.20
Major and minor depressions seem to be implicated in this relation.21
emphasise the importance of identification and treatment of depression in the physically ill.