Elsevier

The Lancet

Volume 392, Issue 10161, 24–30 November 2018, Pages 2299-2312
The Lancet

Seminar
Depression

https://doi.org/10.1016/S0140-6736(18)31948-2Get rights and content

Summary

Major depression is a common illness that severely limits psychosocial functioning and diminishes quality of life. In 2008, WHO ranked major depression as the third cause of burden of disease worldwide and projected that the disease will rank first by 2030.1 In practice, its detection, diagnosis, and management often pose challenges for clinicians because of its various presentations, unpredictable course and prognosis, and variable response to treatment.

Section snippets

Prevalence

The 12-month prevalence of major depressive disorder varies considerably across countries but is approximately 6%, overall.2 The lifetime risk of depression is three times higher (15–18%),3 meaning major depressive disorder is common, with almost one in five people experiencing one episode at some point in their lifetime. Hence, in primary care, one in ten patients, on average, presents with depressive symptoms,4 although the prevalence of depression increases in secondary care settings.

Diagnosis

The two main classificatory diagnostic systems (Diagnostic and Statistical Manual of Mental Disorders [DSM],23 and International Classification of Diseases [ICD]24) rely on the identification of a number of key symptoms (figure 1). Notably, none of the symptoms are pathognomonic of depression, and do feature in other psychiatric and medical illnesses. Therefore, the definition of depression as a disorder is based on symptoms forming a syndrome and causing functional impairment. Some symptoms

Pathology

Understanding of the pathophysiology of major depressive disorder has progressed considerably, but no single model or mechanism can satisfactorily explain all aspects of the disease. Different causes or pathophysiology might underlie episodes in different patients, or even different episodes in the same patient at different times. Psychosocial stressors and biological stressors (eg, post-partum period) can result in different pathogenesis and respond preferentially to different interventions.

Management of major depressive disorder

When treating a depressive episode, the initial objective is the complete remission of depressive symptoms and broadly speaking, this objective can usually be achieved by use of psychological therapy, pharmacotherapy, or both.100, 101, 102 However, before embarking on a specific treatment pathway, it is important to stop the administration of drugs that can potentially lower mood, address any substance misuse, and, when possible, use general measures such as sleep hygiene, regular exercise, and

Pharmacotherapy

The pharmacotherapy for major depressive disorder has been founded on enhancement of monoaminergic neurotransmission.116 But newer antidepressants target other brain systems, like the N-methyl-D-aspartate (NMDA) receptor, melatonin, or gamma-aminobutyric acid (appendix).

Special populations

The manifestations and management of depression are affected by life stage and special circumstances, such as during the perinatal period. For children and adolescents, the clinical presentation of depression and response to treatment can differ from adulthood, because of developmental differences in biology and psychophysiology in children and adolescents, and limited language and experience, which means they are likely to express their distress differently.147, 148 Comorbid medical problems,

Future directions

The fact that major depression affects many people, and has a huge impact on the individuals and imposes an immense economic burden, means that greater efforts are required to improve its diagnosis and management. This need applies especially to low-income and middle-income countries, where health-care resources are limited at every level. The heterogeneity of the illness, the stigma surrounding mental illness, and a collective failure to identify more effective treatments are key challenges.

Search strategy and selection criteria

We searched PubMed for studies published between Jan 1, 2010, and Jan 1, 2018, with the terms “depression”, “depressive disorder”, and “depressive disorder, major”, with specifiers “therapy” and “drug therapy”, as well as “antidepressive agents” and “psychotherapy”. The search excluded articles on depression in the context of bipolar disorder, other psychiatric illnesses (such as schizophrenia), and medical illnesses. We restricted the search to English language publications and focused on

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