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Major depressive disorder

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Major depressive disorder
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{{For|other types of depression|Mood disorder}}{{Distinguish|Depression (mood)}}{{pp-semi-indef}}{{Use dmy dates|date=August 2018}}







factoids
| medication =| prognosis =| frequency = 216 million (2015)| deaths =}}Major depressive disorder (MDD), also known simply as depression, is a mental disorder characterized by at least two weeks of low mood that is present across most situations. It is often accompanied by low self-esteem, loss of interest in normally enjoyable activities, low energy, and pain without a clear cause. People may also occasionally have false beliefs or see or hear things that others cannot. Some people have periods of depression separated by years in which they are normal, while others nearly always have symptoms present. Major depressive disorder can negatively affect a person's personal life, work life, or education, as well as sleeping, eating habits, and general health. Between 2–8% of adults with major depression die by suicide,BOOK, Richards, C. Steven, O'Hara, Michael W., vanc, The Oxford Handbook of Depression and Comorbidity, 2014, Oxford University Press, 978-0-19-979704-2, 254,weblink BOOK, Strakowski, Stephen, Nelson, Erik, vanc, Major Depressive Disorder, 2015, Oxford University Press, 978-0-19-026432-1, PT27,weblink and about 50% of people who die by suicide had depression or another mood disorder.JOURNAL, Bachmann, S, Epidemiology of Suicide and the Psychiatric Perspective, International Journal of Environmental Research and Public Health, 6 July 2018, 15, 7, 1425, 10.3390/ijerph15071425, 29986446, 6068947, Half of all completed suicides are related to depressive and other mood disorders, The cause is believed to be a combination of genetic, environmental, and psychological factors.WEB, Depression,weblink NIMH, 31 July 2016, May 2016, no,weblink" title="web.archive.org/web/20160805065529weblink">weblink 5 August 2016, Risk factors include a family history of the condition, major life changes, certain medications, chronic health problems, and substance abuse. About 40% of the risk appears to be related to genetics. The diagnosis of major depressive disorder is based on the person's reported experiences and a mental status examination.BOOK, Patton, Lauren L., vanc, The ADA Practical Guide to Patients with Medical Conditions, 2015, John Wiley & Sons, 978-1-118-92928-5, 339, 2,weblink There is no laboratory test for major depression. Testing, however, may be done to rule out physical conditions that can cause similar symptoms. Major depression is more severe and lasts longer than sadness, which is a normal part of life. The United States Preventive Services Task Force (USPSTF) recommends screening for depression among those over the age 12,JOURNAL, Siu AL, Bibbins-Domingo K, Grossman DC, Baumann LC, Davidson KW, Ebell M, García FA, Gillman M, Herzstein J, Kemper AR, Krist AH, Kurth AE, Owens DK, Phillips WR, Phipps MG, Pignone MP, Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement, JAMA, 315, 4, 380–87, January 2016, 26813211, 10.1001/jama.2015.18392, JOURNAL, Siu AL, Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement, Annals of Internal Medicine, 164, 5, 360–66, March 2016, 26858097, 10.7326/M15-2957, while a prior Cochrane review found that the routine use of screening questionnaires has little effect on detection or treatment.JOURNAL, Gilbody S, House AO, Sheldon TA, Screening and case finding instruments for depression, The Cochrane Database of Systematic Reviews, 4, CD002792, October 2005, 16235301, 10.1002/14651858.CD002792.pub2, Typically, people are treated with counseling and antidepressant medication. Medication appears to be effective, but the effect may only be significant in the most severely depressed.JOURNAL, Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J, Antidepressant drug effects and depression severity: a patient-level meta-analysis, JAMA, 303, 1, 47–53, January 2010, 20051569, 3712503, 10.1001/jama.2009.1943, JOURNAL, Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT, Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration, PLoS Medicine, 5, 2, e45, February 2008, 18303940, 2253608, 10.1371/journal.pmed.0050045, It is unclear whether medications affect the risk of suicide.JOURNAL, Braun C, Bschor T, Franklin J, Baethge C, Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder, Psychotherapy and Psychosomatics, 85, 3, 171–79, 2016, 27043848, 10.1159/000442293, Types of counseling used include cognitive behavioral therapy (CBT) and interpersonal therapy.JOURNAL, Driessen E, Hollon SD, Cognitive behavioral therapy for mood disorders: efficacy, moderators and mediators, The Psychiatric Clinics of North America, 33, 3, 537–55, September 2010, 20599132, 2933381, 10.1016/j.psc.2010.04.005, If other measures are not effective, electroconvulsive therapy (ECT) may be considered. Hospitalization may be necessary in cases with a risk of harm to self and may occasionally occur against a person's wishes.BOOK, American Psychiatric Association, American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders: Compendium 2006, American Psychiatric Pub, 978-0-89042-385-1, 780,weblink 2006, Major depressive disorder affected approximately 216 million people (3% of the world's population) in 2015.JOURNAL, GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015, Lancet, 388, 10053, 1545–602, October 2016, 27733282, 5055577, 10.1016/S0140-6736(16)31678-6, The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France.JOURNAL, Kessler RC, Bromet EJ, The epidemiology of depression across cultures, Annual Review of Public Health, 34, 119–38, 2013, 23514317, 4100461, 10.1146/annurev-publhealth-031912-114409, Lifetime rates are higher in the developed world (15%) compared to the developing world (11%). It causes the second-most years lived with disability, after lower back pain.JOURNAL, Global Burden of Disease Study 2013 Collaborators, Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013, Lancet, 386, 9995, 743–800, August 2015, 26063472, 4561509, 10.1016/S0140-6736(15)60692-4, The most common time of onset is in a person's 20s and 30s. Females are affected about twice as often as males.{{citation|author=American Psychiatric Association|year=2013|title=Diagnostic and Statistical Manual of Mental Disorders|location=Arlington|publisher=American Psychiatric Publishing|pages=160–68|isbn=978-0-89042-555-8|edition=5th|url=https://www.psychiatry.org/psychiatrists/practice/dsm/dsm-5|accessdate=22 July 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160731072609weblink|archivedate=31 July 2016}} The American Psychiatric Association added "major depressive disorder" to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. It was 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.BOOK, Hersen, Michel, Rosqvist, Johan, vanc, Handbook of Psychological Assessment, Case Conceptualization, and Treatment, Volume 1: Adults, John Wiley & Sons, 978-0-470-17356-5, 32, 2008,weblink Those currently or previously affected may be stigmatized.BOOK, Strakowski, Stephen M., Nelson, Erik, vanc, Major Depressive Disorder, Oxford University Press, 978-0-19-020618-5, Chapter 1,weblink Introduction, 2015, File:Wikipedia-VideoWiki-Major depressive disorder overview.webm|thumb|thumbtime=0:32|upright=1.3|Video summary (script)]]{{TOC limit}}

Signs and symptoms

(File:A woman diagnosed as suffering from melancholia. Colour lith Wellcome L0026686.jpg|thumb|An 1892 lithograph of a woman diagnosed with depression)Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health.BOOK, Depression, National Institute of Mental Health (NIMH),weblink 7 September 2008, yes,weblink" title="web.archive.org/web/20110727123744weblink">weblink 27 July 2011, Its impact on functioning and well-being has been compared to that of other chronic medical conditions, such as diabetes.JOURNAL, Hays RD, Wells KB, Sherbourne CD, Rogers W, Spritzer K, Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses, Archives of General Psychiatry, 52, 1, 11–19, January 1995, 7811158, 10.1001/archpsyc.1995.03950130011002, A person having a major depressive episode usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred.{{Harvnb |American Psychiatric Association|2000a|p=349}} In severe cases, depressed people may have symptoms of psychosis. These symptoms include delusions or, less commonly, hallucinations, usually unpleasant.{{Harvnb |American Psychiatric Association|2000a|p=412}} Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features),JOURNAL, Delgado PL, Schillerstrom J, Cognitive Difficulties Associated With Depression: What Are the Implications for Treatment?, Psychiatric Times, 26, 3, 2009,weblink no,weblink" title="web.archive.org/web/20090722165650weblink">weblink 22 July 2009, withdrawal from social situations and activities, reduced sex drive, irritability,JOURNAL, Judd LL, Schettler PJ, Coryell W, Akiskal HS, Fiedorowicz JG, Overt irritability/anger in unipolar major depressive episodes: past and current characteristics and implications for long-term course, JAMA Psychiatry, 70, 11, 1171–80, November 2013, 24026579, 10.1001/jamapsychiatry.2013.1957, and thoughts of death or suicide. Insomnia is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep.{{Harvnb |American Psychiatric Association|2000a|p=350}} Hypersomnia, or oversleeping, can also happen. Some antidepressants may also cause insomnia due to their stimulating effect.JOURNAL,weblink Insomnia: Assessment and Management in Primary Care, American Family Physician, 59, 11, 3029–38, 1999, 12 November 2014, no,weblink" title="web.archive.org/web/20110726103917weblink">weblink 26 July 2011, {{Anchor|physicalSymptoms}}A 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.JOURNAL, Fisher JC, Powers WE, Tuerk DB, Edgerton MT, Development of a plastic surgical teaching service in a women's correctional institution, American Journal of Surgery, 129, 3, 269–72, March 1975, 1119689, 10.1136/bmj.322.7284.482, 11222428, Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur. Family and friends may notice that the person's behavior is either agitated or lethargic. Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, and a more noticeable slowing of movements.BOOK, Consensus Guidelines for Assessment and Management of Depression in the Elderly, ((Faculty of Psychiatry of Old Age, NSW Branch, RANZCP)), Kitching D, Raphael B, 2001, NSW Health Department, North Sydney, New South Wales, 978-0-7347-3341-2, 2,weblink no,weblink" title="web.archive.org/web/20150401162939weblink">weblink 1 April 2015, Depression often coexists with physical disorders common among the elderly, such as stroke, other cardiovascular diseases, Parkinson's disease, and chronic obstructive pulmonary disease.JOURNAL, Yohannes AM, Baldwin RC, Medical Comorbidities in Late-Life Depression, Psychiatric Times, 25, 14, 2008,weblink Depressed children may often display an irritable mood rather than a depressed one, and show varying symptoms depending on age and situation.{{Harvnb |American Psychiatric Association|2000a|p=354}} Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure. Diagnosis may be delayed or missed when symptoms are interpreted as "normal moodiness."

Associated conditions

Major depression frequently co-occurs with other psychiatric problems. The 1990–92 National Comorbidity Survey (US) reports that half of those with major depression also have lifetime anxiety and its associated disorders such as generalized anxiety disorder.JOURNAL, Kessler RC, Nelson CB, McGonagle KA, Liu J, Swartz M, Blazer DG, Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey, The British Journal of Psychiatry. Supplement, 168, 30, 17–30, June 1996, 8864145, 10.1192/S0007125000298371, 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 suicide attempts.JOURNAL, Hirschfeld RM, The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care, Primary Care Companion to the Journal of Clinical Psychiatry, 3, 6, 244–54, December 2001, 15014592, 181193, 10.4088/PCC.v03n0609, There are increased rates of alcohol and drug abuse and particularly dependence,JOURNAL, Grant BF, Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults, Journal of Substance Abuse, 7, 4, 481–97, 1995, 8838629, 10.1016/0899-3289(95)90017-9, JOURNAL, Boden JM, Fergusson DM, Alcohol and depression, Addiction, 106, 5, 906–14, May 2011, 21382111, 10.1111/j.1360-0443.2010.03351.x, and around a third of individuals diagnosed with ADHD develop comorbid depression.BOOK, Delivered from distraction: Getting the most out of life with Attention Deficit Disorder, Hallowell EM, Ratey JJ, 2005, Ballantine Books, New York, 978-0-345-44231-4, 253–55, Post-traumatic stress disorder and depression often co-occur. Depression may also coexist with attention deficit hyperactivity disorder (ADHD), complicating the diagnosis and treatment of both.JOURNAL, Brunsvold GL, Oepen G, Comorbid Depression in ADHD: Children and Adolescents, Psychiatric Times, 25, 10, 2008,weblink no,weblink" title="web.archive.org/web/20090524050341weblink">weblink 24 May 2009, Depression is also frequently comorbid with alcohol abuse and personality disorders.JOURNAL, Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Sokero TP, Isometsä ET, Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study, The Journal of Clinical Psychiatry, 63, 2, 126–34, February 2002, 11874213, 10.4088/jcp.v63n0207, Depression can also be exacerbated during particular months (usually winter) for those with seasonal affective disorder. While overuse of digital media has been associated with depressive symptoms, digital media may also be utilised in some situations to improve mood.JOURNAL, Cantor, Joanne, Bickham, David, Hoge, Elizabeth, 2017-11-01, Digital Media, Anxiety, and Depression in Children,weblink Pediatrics, en, 140, Supplement 2, S76–S80, 10.1542/peds.2016-1758G, 0031-4005, 29093037, JOURNAL, Elhai, Jon D., Dvorak, Robert D., Levine, Jason C., Hall, Brian J., 2017-01-01, Problematic smartphone use: A conceptual overview and systematic review of relations with anxiety and depression psychopathology, Journal of Affective Disorders, 207, 251–259, 10.1016/j.jad.2016.08.030, 27736736, 0165-0327, Depression and pain often co-occur. One or more pain symptoms are present in 65% of depressed patients, and anywhere from 5 to 85% of patients with pain will be suffering from depression, depending on the setting; there is a lower prevalence in general practice, and higher in specialty clinics. The diagnosis of depression is often delayed or missed, and the outcome can worsen if the depression is noticed but completely misunderstood.JOURNAL, Bair MJ, Robinson RL, Katon W, Kroenke K, Depression and pain comorbidity: a literature review, Archives of Internal Medicine, 163, 20, 2433–45, November 2003, 14609780, 10.1001/archinte.163.20.2433,weblink Depression is also associated with 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, which further increases their risk of medical complications.JOURNAL, Swardfager W, Herrmann N, Marzolini S, Saleem M, Farber SB, Kiss A, Oh PI, Lanctôt KL, Major depressive disorder predicts completion, adherence, and outcomes in cardiac rehabilitation: a prospective cohort study of 195 patients with coronary artery disease, The Journal of Clinical Psychiatry, 72, 9, 1181–88, September 2011, 21208573, 10.4088/jcp.09m05810blu, In addition, cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.JOURNAL, Schulman J, Shapiro BA, 2008, Psychiatric Times, 25, 9, Depression and Cardiovascular Disease: What Is the Correlation?,weblink

Cause

File:Diathesis_stress_model_cup_analogy.svg|thumb|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.BOOK, Hankin, Benjamin L., Abela, John R. Z., Development of Psychopathology: A Vulnerability-Stress Perspective, 2005, SAGE Publications, 9781412904902, 32–34,weblink en, )The cause of major depressive disorder is unknown. The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression.WEB, Department of Health and Human Services, 1999,weblink The fundamentals of mental health and mental illness, Mental Health: A Report of the Surgeon General, 11 November 2008, no,weblink" title="web.archive.org/web/20081217031913weblink">weblink 17 December 2008, 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,JOURNAL, Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R, Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene, Science, 301, 5631, 386–89, July 2003, 12869766, 10.1126/science.1083968, 2003Sci...301..386C, JOURNAL, Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, Deyoung CG, Klinteberg BA, Oreland L, Ruchkin VV, Grigorenko EL, Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees, Psychological Science, 19, 1, 62–69, January 2008, 18181793, 10.1111/j.1467-9280.2008.02047.x,weblinkweblink" title="web.archive.org/web/20081217031910weblink">weblink no, 17 December 2008, implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood.WEB, Slavich GM, 2004,weblink Deconstructing depression: A diathesis-stress perspective (Opinion), APS Observer, 11 November 2008, no,weblink" title="web.archive.org/web/20110511233644weblink">weblink 11 May 2011, Childhood abuse, either physical, sexual or psychological, are all risk factors for depression, among other psychiatric issues that co-occur such as anxiety and drug abuse. Childhood trauma also correlates with severity of depression, lack of response to treatment and length of illness. However, some are more susceptible to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.JOURNAL, Saveanu RV, Nemeroff CB, Etiology of depression: genetic and environmental factors, The Psychiatric Clinics of North America, 35, 1, 51–71, March 2012, 22370490, 10.1016/j.psc.2011.12.001,weblink

Genetics

Family and twin studies find that nearly 40% of individual differences in risk for major depressive disorder can be explained by genetic factors.JOURNAL, Sullivan PF, Neale MC, Kendler KS, October 2000, Genetic epidemiology of major depression: review and meta-analysis, The American Journal of Psychiatry, 157, 10, 1552–62, 10.1176/appi.ajp.157.10.1552, 11007705, Like most psychiatric disorders, major depressive disorder is likely to be influenced by many individual genetic changes. In 2018, a genome-wide association study discovered 44 variants in the genome linked to risk for major depression.JOURNAL, Wray, NR, May 2018, Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression,weblink Nature Genetics, 50, 5, 668–681, 10.1038/s41588-018-0090-3, 5934326, 29700475, This was followed by a 2019 study that found 102 variants in the genome linked to depression.JOURNAL, Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, etal, March 2019, Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions, Nature Neuroscience, 22, 3, 343–352, 10.1038/s41593-018-0326-7, 30718901, {{update after|2019|09|01|reason=embargo on pmc lifted}} These results have enabled scientists to calculate polygenic risk scores, which combine the estimated effects across the genome into a single score in order to estimate a person’s genetic liability for depression. Although these scores explain a small proportion (less than 2%) of individual differences in the risk for major depressive disorder.The 5-HTTLPR, or serotonin transporter promoter gene's short allele has been associated with increased risk of depression. However, since the 1990s, results have been inconsistent, with three recent reviews finding an effect and two finding none.JOURNAL, Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B, The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication, Archives of General Psychiatry, 62, 5, 529–35, May 2005, 15867106, 10.1001/archpsyc.62.5.529, JOURNAL, Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR, Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis, JAMA, 301, 23, 2462–71, June 2009, 19531786, 2938776, 10.1001/jama.2009.878, JOURNAL, Munafò MR, Durrant C, Lewis G, Flint J, Gene X environment interactions at the serotonin transporter locus, Biological Psychiatry, 65, 3, 211–19, February 2009, 18691701, 10.1016/j.biopsych.2008.06.009, JOURNAL, Karg K, Burmeister M, Shedden K, Sen S, The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation, Archives of General Psychiatry, 68, 5, 444–54, May 2011, 21199959, 10.1001/archgenpsychiatry.2010.189, 3740203, Other genes that have been linked to a gene-environment interaction include CRHR1, FKBP5 and BDNF, the first two of which are related to the stress reaction of the HPA axis, and the latter of which is involved in neurogenesis. There is no conclusive effects of candidate gene on depression, either alone or in combination with life stress.JOURNAL, Culverhouse RC, Saccone NL, Horton AC, Ma Y, Anstey KJ, Banaschewski T, etal, January 2018, Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression, Molecular Psychiatry, 23, 1, 133–142, 10.1038/mp.2017.44, 5628077, 28373689, Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings.JOURNAL, Duncan LE, Keller MC, October 2011, A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry, The American Journal of Psychiatry, 168, 10, 1041–9, 10.1176/appi.ajp.2011.11020191, 3222234, 21890791, There are also other efforts to examine interactions between life stress and polygenic risk for depression.JOURNAL, Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PA, Sullivan PF, Strohmaier J, Ripke S, Rietschel M, Nivard MG, Mullins N, Montgomery GW, Henders AK, Heat AC, Fisher HL, Dunn EC, Byrne EM, etal, July 2018, Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium, Biological Psychiatry, 84, 2, 138–147, 10.1016/j.biopsych.2017.09.009, 5862738, 29129318,

Other health problems

Depression may also come secondary to a chronic or terminal medical condition, such as HIV/AIDS or asthma, and may be labeled "secondary depression."JOURNAL, Simon GE, Treating depression in patients with chronic disease: recognition and treatment are crucial; depression worsens the course of a chronic illness, The Western Journal of Medicine, 175, 5, 292–93, November 2001, 11694462, 1071593, 10.1136/ewjm.175.5.292, JOURNAL, Clayton PJ, Lewis CE, The significance of secondary depression, Journal of Affective Disorders, 3, 1, 25–35, March 1981, 6455456, 10.1016/0165-0327(81)90016-1, It is unknown whether the underlying diseases induce depression through effect on quality of life, of through shared etiologies (such as degeneration of the basal ganglia in Parkinson's disease or immune dysregulation in asthma).JOURNAL, Kewalramani A, Bollinger ME, Postolache TT, Asthma and Mood Disorders, International Journal of Child Health and Human Development, 1, 2, 115–23, 1 January 2008, 19180246, 2631932, Depression may also be iatrogenic (the result of healthcare), such as drug-induced depression. Therapies associated with depression include interferons, beta-blockers, isotretinoin, contraceptives,JOURNAL, Rogers D, Pies R, General medical with depression drugs associated, Psychiatry, 5, 12, 28–41, December 2008, 19724774, 2729620, cardiac agents, anticonvulsants, antimigraine drugs, antipsychotics, and hormonal agents such as gonadotropin-releasing hormone agonist.BOOK, Botts S, Ryan M, Drug-Induced Diseases Section IV: Drug-Induced Psychiatric Diseases Chapter 18: Depression,weblinkweblink" title="web.archive.org/web/20101223035009weblink">weblink yes, 23 December 2010, 1–23, Drug abuse in early age is also associated with increased risk of developing depression later in life.JOURNAL, Brook DW, Brook JS, Zhang C, Cohen P, Whiteman M, Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders, Archives of General Psychiatry, 59, 11, 1039–44, November 2002, 12418937, 10.1001/archpsyc.59.11.1039, Depression that occurs as a result of pregnancy is called postpartum depression, and is thought to be the result of hormonal changes associated with pregnancy.JOURNAL, Meltzer-Brody S, New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum, Dialogues in Clinical Neuroscience, 13, 1, 89–100, 9 January 2017, 21485749, 3181972, Seasonal affective disorder, a type of depression associated with seasonal changes in sunlight, is thought to be the result of decreased sunlight.JOURNAL, Melrose S, Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches, Depression Research and Treatment, 2015, 178564, 1 January 2015, 26688752, 4673349, 10.1155/2015/178564,

Pathophysiology

{{see|Biology of depression|Epigenetics of depression}}The pathophysiology of depression is not yet understood, but the current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA axis dysfunction and structural or functional abnormalities of emotional circuits.The monoamine theory, derived from the efficacy of monoaminergic drugs in treating depression, was the dominant theory until recently. The theory postulates that insufficient activity of monoamine neurotransmitters is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. Firstly, acute depletion of tryptophan, a necessary precursor of serotonin, a monoamine, can cause depression in those in remission or relatives of depressed patients; this suggests that decreased serotonergic neurotransmission is important in depression.JOURNAL, Ruhé HG, Mason NS, Schene AH, Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies, Molecular Psychiatry, 12, 4, 331–59, April 2007, 17389902, 10.1038/sj.mp.4001949, Secondly, the correlation between depression risk and polymorphisms in the 5-HTTLPR gene, which codes for serotonin receptors, suggests a link. Third, decreased size of the locus coeruleus, decreased activity of tyrosine hydroxylase, increased density of alpha-2 adrenergic receptor, and evidence from rat models suggest decreased adrenergic neurotransmission in depression.JOURNAL, Delgado PL, Moreno FA, Role of norepinephrine in depression, The Journal of Clinical Psychiatry, 61 Suppl 1, 5–12, 2000, 10703757, 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,JOURNAL, Savitz JB, Drevets WC, Neuroreceptor imaging in depression, Neurobiology of Disease, 52, 49–65, April 2013, 22691454, 10.1016/j.nbd.2012.06.001, and polymorphism of dopamine receptor genes implicate dopamine, another monoamine, in depression.JOURNAL, Hasler G, Pathophysiology of depression: do we have any solid evidence of interest to clinicians?, World Psychiatry, 9, 3, 155–61, October 2010, 20975857, 2950973, 10.1002/j.2051-5545.2010.tb00298.x, JOURNAL, Dunlop BW, Nemeroff CB, The role of dopamine in the pathophysiology of depression, Archives of General Psychiatry, 64, 3, 327–37, March 2007, 17339521, 10.1001/archpsyc.64.3.327,weblink Lastly, increased activity of monoamine oxidase, which degrades monoamines, has been associated with depression.JOURNAL, Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S, Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression, Archives of General Psychiatry, 63, 11, 1209–16, November 2006, 17088501, 10.1001/archpsyc.63.11.1209, However, this theory is inconsistent with the fact that serotonin depletion does not cause depression in healthy persons, the fact 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.BOOK, Kenneth L, Davis, Dennis, Charney MD, Joseph T, Coyle, Charles, Nemeroff, vanc, Neuropsychopharmacology: the fifth generation of progress: an official publication of the American College of Neuropsychopharmacology, 2002, Lippincott Williams & Wilkins, Philadelphia, 978-0-7817-2837-9, 1139–63, 5th, 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.JOURNAL, Adell A, Revisiting the role of raphe and serotonin in neuropsychiatric disorders, The Journal of General Physiology, 145, 4, 257–59, April 2015, 25825168, 10.1085/jgp.201511389, 4380212, 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 depressed patients that normalized with SSRI treatment, and the preference for carbohydrates in depressed patients.JOURNAL, Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA, Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response, Neuroscience and Biobehavioral Reviews, 51, 164–88, April 2015, 25625874, 10.1016/j.neubiorev.2015.01.018, Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.JOURNAL, Lacasse JR, Leo J, Serotonin and depression: a disconnect between the advertisements and the scientific literature, PLoS Medicine, 2, 12, e392, December 2005, 16268734, 1277931, 10.1371/journal.pmed.0020392, Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior (which shares overlap with depression).JOURNAL, Krishnadas R, Cavanagh J, Depression: an inflammatory illness?, Journal of Neurology, Neurosurgery, and Psychiatry, 83, 5, 495–502, May 2012, 22423117, 10.1136/jnnp-2011-301779, JOURNAL, Patel A, Review: the role of inflammation in depression, Psychiatria Danubina, 25 Suppl 2, S216–23, September 2013, 23995180, JOURNAL, Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL, A meta-analysis of cytokines in major depression, Biological Psychiatry, 67, 5, 446–57, March 2010, 20015486, 10.1016/j.biopsych.2009.09.033, The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors in treating depression,JOURNAL, Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J, Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials, JAMA Psychiatry, 71, 12, 1381–91, December 2014, 25322082, 10.1001/jamapsychiatry.2014.1611,weblink and normalization of cytokine levels after successful treatment further suggest immune system abnormalities in depression.JOURNAL, Raedler TJ, Inflammatory mechanisms in major depressive disorder, Current Opinion in Psychiatry, 24, 6, 519–25, November 2011, 21897249, 10.1097/YCO.0b013e32834b9db6, 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 depressed patients. However, this abnormality is not adequate as a diagnosis tool, because its sensitivity is only 44%.JOURNAL, Arana GW, Baldessarini RJ, Ornsteen M, The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review, Archives of General Psychiatry, 42, 12, 1193–204, December 1985, 3000317, 10.1001/archpsyc.1985.01790350067012, JOURNAL, Arana GW, Baldessarini RJ, Ornsteen M, The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review, Archives of General Psychiatry, 42, 12, 1193–204, December 1985, 3000317, 10.1001/archpsyc.1985.01790350067012, These stress-related abnormalities have been hypothesized to be the cause of hippocampal volume reductions seen in depressed patients.JOURNAL, Varghese FP, Brown ES, The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians, Primary Care Companion to the Journal of Clinical Psychiatry, 3, 4, 151–55, August 2001, 15014598, 181180, 10.4088/pcc.v03n0401, Furthermore, a meta-analysis yielded decreased dexamethasone suppression, and increased response to psychological stressors.JOURNAL, Lopez-Duran NL, Kovacs M, George CJ, Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis, Psychoneuroendocrinology, 34, 9, 1272–83, October 2009, 19406581, 2796553, 10.1016/j.psyneuen.2009.03.016, Further abnormal results have been obscured with the cortisol awakening response, with increased response being associated with depression.JOURNAL, Dedovic K, Ngiam J, The cortisol awakening response and major depression: examining the evidence, Neuropsychiatric Disease and Treatment, 11, 1181–89, 14 May 2015, 25999722, 4437603, 10.2147/NDT.S62289, 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.JOURNAL, Mayberg HS, Limbic-cortical dysregulation: a proposed model of depression, The Journal of Neuropsychiatry and Clinical Neurosciences, 9, 3, 471–81, 1 August 1997, 9276848, 10.1176/jnp.9.3.471, Another model, the "Corito-Striatal model", suggests that abnormalities of the prefrontal cortex in regulating striatal and subcortical structures results in depression.JOURNAL, Graham J, Salimi-Khorshidi G, Hagan C, Walsh N, Goodyer I, Lennox B, Suckling J, Meta-analytic evidence for neuroimaging models of depression: state or trait?, Journal of Affective Disorders, 151, 2, 423–31, November 2013, 23890584, 10.1016/j.jad.2013.07.002, 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.JOURNAL, Hamilton JP, Etkin A, Furman DJ, Lemus MG, Johnson RF, Gotlib IH, Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data, The American Journal of Psychiatry, 169, 7, 693–703, July 2012, 22535198, 10.1176/appi.ajp.2012.11071105,

Diagnosis

Clinical assessment

{{further|Rating scales for depression}}A diagnostic assessment may be conducted by a suitably trained general practitioner, or by a psychiatrist or psychologist, who records the person's current circumstances, biographical history, current symptoms, and family history. The broad clinical aim is to formulate the relevant biological, psychological, and social factors that may be impacting on the individual's mood. The assessor may also discuss the person's current ways of regulating mood (healthy or otherwise) such as 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. Specialist mental health services are rare in rural areas, and thus diagnosis and management is left largely to primary-care clinicians.JOURNAL, Kaufmann IM, Rural psychiatric services. A collaborative model, Canadian Family Physician, 39, 1957–61, September 1993, 8219844, 2379905, This issue is even more marked in developing countries.WEB,weblink Call for action over Third World depression, 11 October 2008, 1 November 1999, BBC News (Health), British Broadcasting Corporation (BBC), no,weblink" title="web.archive.org/web/20080513222415weblink">weblink 13 May 2008, The mental health examination may include the use of a rating scale such as the Hamilton Rating Scale for Depression,JOURNAL, Zimmerman M, Chelminski I, Posternak M, A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression, The Journal of Nervous and Mental Disease, 192, 9, 595–601, September 2004, 15348975, 10.1097/01.nmd.0000138226.22761.39, the Beck Depression InventoryJOURNAL, McPherson A, Martin CR, A narrative review of the Beck Depression Inventory (BDI) and implications for its use in an alcohol-dependent population, Journal of Psychiatric and Mental Health Nursing, 17, 1, 19–30, February 2010, 20100303, 10.1111/j.1365-2850.2009.01469.x, or the Suicide Behaviors Questionnaire-Revised.JOURNAL, Osman A, Bagge CL, Gutierrez PM, Konick LC, Kopper BA, Barrios FX, The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with clinical and nonclinical samples, Assessment, 8, 4, 443–54, December 2001, 11785588, 10.1177/107319110100800409, The score on a rating scale alone is insufficient to diagnose depression to the satisfaction of the DSM or ICD, but it provides 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.JOURNAL, Sharp LK, Lipsky MS, Screening for depression across the lifespan: a review of measures for use in primary care settings, American Family Physician, 66, 6, 1001–08, September 2002, 12358212, Primary-care physicians and other non-psychiatrist physicians have more difficulty with underrecognition and undertreatment of depression compared to psychiatric physicians, in part because of the physical symptoms that often accompany depression, in addition to many potential patient, provider, and system barriers. A review found that non-psychiatrist physicians miss about two-thirds of cases, though this has improved somewhat in more recent studies.JOURNAL, Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A, Recognition of depression by non-psychiatric physicians—a systematic literature review and meta-analysis, Journal of General Internal Medicine, 23, 1, 25–36, January 2008, 17968628, 2173927, 10.1007/s11606-007-0428-5, Before diagnosing a major depressive disorder, in general a doctor performs a medical examination and selected investigations to rule out other causes of 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.JOURNAL, Dale J, Sorour E, Milner G, 2008, Do psychiatrists perform appropriate physical investigations for their patients? A review of current practices in a general psychiatric inpatient and outpatient setting, Journal of Mental Health, 17, 3, 293–98, 10.1080/09638230701498325, Adverse affective reactions to medications or alcohol misuse are often ruled out, as well. Testosterone levels may be evaluated to diagnose hypogonadism, a cause of depression in men.JOURNAL, Orengo CA, Fullerton G, Tan R, Male depression: a review of gender concerns and testosterone therapy, Geriatrics, 59, 10, 24–30, October 2004, 15508552, Vitamin D levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression.JOURNAL, Parker GB, Brotchie H, Graham RK, Vitamin D and depression, Journal of Affective Disorders, 208, 56–61, January 2017, 27750060, 10.1016/j.jad.2016.08.082, 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.JOURNAL, Reid LM, Maclullich AM, Subjective memory complaints and cognitive impairment in older people, Dementia and Geriatric Cognitive Disorders, 22, 5–6, 471–85, 2006, 17047326, 10.1159/000096295, JOURNAL, Katz IR, Diagnosis and treatment of depression in patients with Alzheimer's disease and other dementias, The Journal of Clinical Psychiatry, 59 Suppl 9, 38–44, 1998, 9720486, Cognitive testing and brain imaging can help distinguish depression from dementia.JOURNAL, Wright SL, Persad C, Distinguishing between depression and dementia in older persons: neuropsychological and neuropathological correlates, Journal of Geriatric Psychiatry and Neurology, 20, 4, 189–98, December 2007, 18004006, 10.1177/0891988707308801, A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.{{Harvnb |Sadock|2002|p=108}} In general, investigations are not repeated for a subsequent episode unless there is a medical indication.No biological tests confirm major depression.{{Harvnb |Sadock|2002|p=260}} Biomarkers of depression have been sought to provide an objective method of diagnosis. There are several potential biomarkers, including brain-derived neurotrophic factor and various functional MRI (fMRI) techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. In their subjects, the authors of that study were able to achieve a sensitivity of 80% and a specificity of 87%, corresponding to a negative predictive value of 98% and a positive predictive value of 32% (positive and negative likelihood ratios were 6.15, 0.23, respectively). However, much more research is needed before these tests can be used clinically.JOURNAL, Hahn T, Marquand AF, Ehlis AC, Dresler T, Kittel-Schneider S, Jarczok TA, Lesch KP, Jakob PM, Mourao-Miranda J, Brammer MJ, Fallgatter AJ, Integrating neurobiological markers of depression, Archives of General Psychiatry, 68, 4, 361–68, April 2011, 21135315, 10.1001/archgenpsychiatry.2010.178,weblink Klaus-Peter Lesch,

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 and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems which uses the name depressive episode for a single episode and recurrent depressive disorder for repeated episodes.WEB,weblink Mental and behavioural disorders: Mood [affective] disorders, World Health Organization, 2010, 8 November 2008, no,weblink" title="web.archive.org/web/20141102133725weblink">weblink 2 November 2014, The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,{{Harvnb |Sadock|2002|p=288}} and the authors of both have worked towards conforming one with the other.{{Harvnb |American Psychiatric Association|2000a|p=xxix}}Both DSM-5 and ICD-10 mark out typical (main) depressive symptoms. ICD-10 defines three typical depressive symptoms (depressed mood, anhedonia, and reduced energy), two of which should be present to determine the depressive disorder diagnosis.WEB, The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines,weblink 2010, World Health Organization, 12 November 2014, no,weblink" title="web.archive.org/web/20140323025330weblink">weblink 23 March 2014, The ICD-10 classification of mental and behavioral disorders. Clinical description and diagnostic guideline. Geneva: World Health Organization, 1992 According to DSM-5, there are two main depressive symptoms- a depressed mood and loss of interest/pleasure in activities (anhedonia). 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.WEB,weblink Diagnostic Criteria for Major Depressive Disorder and Depressive Episodes, City of Palo Alto Project Safety Net, Major depressive disorder is classified as a mood disorder in DSM-5.JOURNAL, Parker, George F., 2014-06-01, DSM-5 and Psychotic and Mood Disorders,weblink Journal of the American Academy of Psychiatry and the Law Online, en, 42, 2, 182–190, 1093-6793, 24986345, The diagnosis hinges on the presence of single or recurrent major depressive episodes. 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. The ICD-10 system does not use the term major depressive disorder but lists very similar criteria for the diagnosis of a depressive episode (mild, moderate or severe); the term recurrent may be added if there have been multiple episodes without mania.

Major depressive episode

A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. 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. If the patient 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".{{Harvnb |Parker|1996|p=173}}DSM-IV-TR excludes cases where the symptoms are a result of bereavement, although it is possible for normal bereavement to evolve into a depressive episode if the mood persists and the characteristic features of a major depressive episode develop.{{Harvnb |American Psychiatric Association|2000a|p=352}} The criteria were criticized because they do not take into account any other aspects of the personal and social context in which depression can occur.JOURNAL, Wakefield JC, Schmitz MF, First MB, Horwitz AV, April 2007, Extending the bereavement exclusion for major depression to other losses: evidence from the National Comorbidity Survey, Archives of General Psychiatry, 64, 4, 433–40, 10.1001/archpsyc.64.4.433, 17404120, The Washington Post, 3 April 2007,weblink In addition, some studies have found little empirical support for the DSM-IV cut-off criteria, indicating they are a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration.JOURNAL, Kendler KS, Gardner CO, February 1998, Boundaries of major depression: an evaluation of DSM-IV criteria, The American Journal of Psychiatry, 155, 2, 172–77, 10.1176/ajp.155.2.172, 9464194, 2019-05-25, Bereavement is no longer an exclusion criterion in DSM-5, and it is now 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;{{Harvnb |Sadock|2002|p=552}} recurrent brief depression, consisting of briefer depressive episodes;{{Harvnb |American Psychiatric Association|2000a|p=778}}JOURNAL, Carta MG, Altamura AC, Hardoy MC, Pinna F, Medda S, Dell'Osso L, Carpiniello B, Angst J, Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample, European Archives of Psychiatry and Clinical Neuroscience, 253, 3, 149–53, June 2003, 12904979, 10.1007/s00406-003-0418-5, minor depressive disorder, whereby only some symptoms of major depression are present;JOURNAL, Rapaport MH, Judd LL, Schettler PJ, Yonkers KA, Thase ME, Kupfer DJ, Frank E, Plewes JM, Tollefson GD, Rush AJ, A descriptive analysis of minor depression, The American Journal of Psychiatry, 159, 4, 637–43, April 2002, 11925303, 10.1176/appi.ajp.159.4.637, and adjustment disorder with depressed mood, which denotes low mood resulting from a psychological response to an identifiable event or stressor.{{Harvnb |American Psychiatric Association|2000a|p=355}} Three new depressive disorders were added to the DSM-5: disruptive mood dysregulation disorder, classified by significant childhood irritability and tantrums,WEB,weblink NIMH » Disruptive Mood Dysregulation Disorder, www.nimh.nih.gov, 2019-02-21, premenstrual dysphoric disorder (PMDD), causing periods of anxiety, depression, or irritability in the week or two before a woman's menstruation,WEB,weblink Premenstrual dysphoric disorder (PMDD), 2017-07-12, womenshealth.gov, en, 2019-02-21, and persistent depressive disorder.

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.{{Harvnb |American Psychiatric Association|2000a|pp=419–20}}
  • "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 social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.{{Harvnb |American Psychiatric Association|2000a|pp=421–22}}
  • "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.{{Harvnb |American Psychiatric Association|2000a|pp=417–18}}
  • "Depression with anxious distress" was added into the DSM-V as a means to emphasize the common co-occurrence between depression or mania and anxiety, as well as the risk of suicide of depressed individuals with anxiety. Specifying in such a way can also help with the prognosis of those diagnosed with a depressive or bipolar disorder.
  • "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 in order to not exclude cases of depressed woman during pregnancy.BOOK, Diagnostic and statistical manual of mental disorders : DSM-5., DSM-5 Task Force, 2013, American Psychiatric Association, 9780890425541, 1026055291, Depression with peripartum onset has an incidence rate of 10–15% among new mothers. The DSM-V mandates that, in order to qualify as depression with peripartum onset, onset occur during pregnancy or within one month of delivery. It has been said that postpartum depression can last as long as three months.WEB, Nonacs, Ruta M,weblink eMedicine, Postpartum depression, 4 December 2007, 30 October 2008, no,weblink" title="web.archive.org/web/20081013205912weblink">weblink 13 October 2008,
  • "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.{{Harvnb |American Psychiatric Association|2000a|p=425}}

Screening

In 2016, the United States Preventive Services Task Force (USPSTF) recommended screening in the adult populations with evidence that it increases the detection of people with depression and with proper treatment improves outcomes. They recommend screening in those between the age of 12 to 18 as well.A Cochrane review from 2005 found screening programs do not significantly improve detection rates, treatment, or outcome.

Differential diagnoses

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). 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. Bipolar disorder, also known as manic–depressive disorder, is a condition in which depressive phases alternate with periods of mania or hypomania. Although depression is currently categorized as a separate disorder, there is ongoing debate because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a mood disorder continuum.JOURNAL, Akiskal HS, Benazzi F, The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum, Journal of Affective Disorders, 92, 1, 45–54, May 2006, 16488021, 10.1016/j.jad.2005.12.035, Further differential diagnoses involve chronic fatigue syndrome.JOURNAL, Hawk C, Jason LA, Torres-Harding S, Differential diagnosis of chronic fatigue syndrome and major depressive disorder, International Journal of Behavioral Medicine, 13, 3, 244–51, 1 January 2006, 17078775, 10.1207/s15327558ijbm1303_8, 10.1.1.574.3376, Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications, and substance abuse. 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, drug of abuse, or exposure to a toxin, it is then diagnosed as a specific mood disorder (previously called substance-induced mood disorder in the DSM-IV-TR).

Prevention

Preventative efforts may result in decreases in rates of the condition of between 22 and 38%. Eating large amounts of fish may also reduce the risk.JOURNAL, Li F, Liu X, Zhang D, Fish consumption and risk of depression: a meta-analysis, Journal of Epidemiology and Community Health, 70, 3, 299–304, March 2016, 26359502, 10.1136/jech-2015-206278, Behavioral interventions, such as interpersonal therapy and cognitive-behavioral therapy, are effective at preventing new onset depression.JOURNAL, Cuijpers P, van Straten A, Smit F, Mihalopoulos C, Beekman A, Preventing the onset of depressive disorders: a meta-analytic review of psychological interventions, The American Journal of Psychiatry, 165, 10, 1272–80, October 2008, 18765483, 10.1176/appi.ajp.2008.07091422, 1871/16952, JOURNAL, Muñoz RF, Beardslee WR, Leykin Y, Major depression can be prevented, The American Psychologist, 67, 4, 285–95, May–June 2012, 22583342, 4533896, 10.1037/a0027666, CONFERENCE, Cuijpers, P, Prevention and early treatment of mental ill-health,weblink PSYCHOLOGY FOR HEALTH: Contributions to Policy Making, Brussels, 20 September 2012, no,weblink" title="web.archive.org/web/20130512015105weblink">weblink 12 May 2013, 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.JOURNAL, Griffiths KM, Farrer L, Christensen H, 2010, 192, 11, 4–11, The efficacy of internet interventions for depression and anxiety disorders: a review of randomised controlled trials, Medical Journal of Australia,weblink 12 November 2014, no,weblink 12 November 2014, However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behavior-oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. In addition, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates, and had a well-defined intervention.WEB, Jané-Llopis E, Hosman C, Jenkins R, Anderson P, 2003,weblink Predictors of efficacy in depression prevention programmes, British Journal of Psychiatry, 2 April 2009, no,weblink" title="web.archive.org/web/20090326083702weblink">weblink 26 March 2009, 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.JOURNAL, Cuijpers P, Muñoz RF, Clarke GN, Lewinsohn PM, Psychoeducational treatment and prevention of depression: the "Coping with Depression" course thirty years later, Clinical Psychology Review, 29, 5, 449–58, July 2009, 19450912, 10.1016/j.cpr.2009.04.005,

Management

The three most common treatments for depression are psychotherapy, medication, and electroconvulsive therapy. Psychotherapy is the treatment of choice (over medication) for people under 18. 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:
* 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.WEB,weblink 20 March 2013, Depression, National Institute for Health and Care Excellence, December 2004,weblink" title="web.archive.org/web/20081115042517weblink">weblink 15 November 2008, no, 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 patient preference. Options may include pharmacotherapy, psychotherapy, exercise, electroconvulsive therapy (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 patients with severe depression unless ECT is planned. There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care.JOURNAL, Archer J, Bower P, Gilbody S, Lovell K, Richards D, Gask L, Dickens C, Coventry P, Collaborative care for depression and anxiety problems, The Cochrane Database of Systematic Reviews, 10, CD006525, October 2012, 23076925, 10.1002/14651858.CD006525.pub2, 10871/13751, Treatment options are much 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.JOURNAL, Patel V, Araya R, Bolton P, Treating depression in the developing world, Tropical Medicine & International Health, 9, 5, 539–41, May 2004, 15117296, 10.1111/j.1365-3156.2004.01243.x, A 2014 Cochrane review found insufficient evidence to determine the effectiveness of psychological versus medical therapy in children.JOURNAL, Cox GR, Callahan P, Churchill R, Hunot V, Merry SN, Parker AG, Hetrick SE, Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents, The Cochrane Database of Systematic Reviews, 11, 11, CD008324, November 2014, 25433518, 10.1002/14651858.CD008324.pub3,

Lifestyle

{{further|Neurobiological effects of physical exercise#Major depressive disorder}}Physical exercise is recommended for management of mild depression,WEB,weblink Management of depression in primary and secondary care, 4 November 2008, National Clinical Practice Guideline Number 23, National Institute for Health and Clinical Excellence, 2007, no,weblink" title="web.archive.org/web/20081217031910weblink">weblink 17 December 2008, and has a moderate effect on symptoms. Exercise has also been found to be effective for (unipolar) major depression.JOURNAL, Josefsson T, Lindwall M, Archer T, Physical exercise intervention in depressive disorders: meta-analysis and systematic review, Scandinavian Journal of Medicine & Science in Sports, 24, 2, 259–72, April 2014, 23362828, 10.1111/sms.12050, It is equivalent to the use of medications or psychological therapies in most people. In older people it does appear to decrease depression.JOURNAL, Bridle C, Spanjers K, Patel S, Atherton NM, Lamb SE, Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials, The British Journal of Psychiatry, 201, 3, 180–85, September 2012, 22945926, 10.1192/bjp.bp.111.095174, Exercise may be recommended to people who are willing, motivated, and physically healthy enough to participate in an exercise program as treatment.There is a small amount of evidence that skipping a night's sleep may improve depressive symptoms, 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.JOURNAL, Giedke H, Schwärzler F, Therapeutic use of sleep deprivation in depression, Sleep Medicine Reviews, 6, 5, 361–77, October 2002, 12531127, 10.1053/smrv.2002.0235, harv, In observational studies, smoking cessation has benefits in depression as large as or larger than those of medications.JOURNAL, Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P, Change in mental health after smoking cessation: systematic review and meta-analysis, BMJ, 348, feb13 1, g1151, February 2014, 24524926, 3923980, 10.1136/bmj.g1151, Besides exercise, sleep and diet may play a role in depression, and interventions in these areas may be an effective add-on to conventional methods.JOURNAL, Lopresti, Hood, Drummond, vanc, 3) A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise, Journal of Affective Disorders, 1 January 2006, 148, 1, 12–27,weblink no,weblink" title="web.archive.org/web/20170109183840weblink">weblink 9 January 2017, 10.1016/j.jad.2013.01.014, 23415826,

Counseling

Psychotherapy can be delivered to individuals, groups, or families by mental health professionals. A 2015 review found that cognitive behavioral therapy appears to be similar to antidepressant medication in terms of effect.JOURNAL, Amick HR, Gartlehner G, Gaynes BN, Forneris C, Asher GN, Morgan LC, Coker-Schwimmer E, Boland E, Lux LJ, Gaylord S, Bann C, Pierl CB, Lohr KN, Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis, BMJ, 351, h6019, December 2015, 26645251, 4673103, 10.1136/bmj.h6019, A 2012 review found psychotherapy to be better than no treatment but not other treatments.JOURNAL, Khan A, Faucett J, Lichtenberg P, Kirsch I, Brown WA, A systematic review of comparative efficacy of treatments and controls for depression, PLOS ONE, 7, 7, e41778, 30 July 2012, 22860015, 3408478, 10.1371/journal.pone.0041778, 2012PLoSO...741778K, With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.JOURNAL, Thase ME, When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder?, The Psychiatric Quarterly, 70, 4, 333–46, 1999, 10587988, 10.1023/A:1022042316895, ENCYCLOPEDIA, Cordes J, Encyclopedia of Sciences and Religions, 610–16, 2013, 10.1007/978-1-4020-8265-8_301, Depression, 978-1-4020-8264-1, A 2014 Cochrane review found that work-directed interventions combined with clinical interventions helped to reduce sick days taken by people with depression.JOURNAL, Nieuwenhuijsen K, Faber B, Verbeek JH, Neumeyer-Gromen A, Hees HL, Verhoeven AC, van der Feltz-Cornelis CM, Bültmann U, Interventions to improve return to work in depressed people, The Cochrane Database of Systematic Reviews, 12, 12, CD006237, December 2014, 25470301, 10.1002/14651858.CD006237.pub3, There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of treatment-resistant depression in the short term.JOURNAL, Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N, Psychological therapies for treatment-resistant depression in adults, The Cochrane Database of Systematic Reviews, 5, CD010558, May 2018, 29761488, 6494651, 10.1002/14651858.CD010558.pub2, Psychotherapy has been shown to be effective in older people.JOURNAL, Wilson KC, Mottram PG, Vassilas CA, Psychotherapeutic treatments for older depressed people, The Cochrane Database of Systematic Reviews, 23, 1, CD004853, January 2008, 18254062, 10.1002/14651858.CD004853.pub2, JOURNAL, Cuijpers P, van Straten A, Smit F, Psychological treatment of late-life depression: a meta-analysis of randomized controlled trials, International Journal of Geriatric Psychiatry, 21, 12, 1139–49, December 2006, 16955421, 10.1002/gps.1620, 1871/16894, Successful psychotherapy appears to reduce the recurrence of depression even after it has been terminated or replaced by occasional booster sessions.

Cognitive behavioral therapy

{{See also|Behavioral theories of depression}}Cognitive behavioral therapy (CBT) currently 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.weblink" title="web.archive.org/web/20110726055131weblink">Childhood Depression. abct.org. Last updated: 30 July 2010 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.BOOK, NICE, NICE guidelines: Depression in children and adolescents, NICE, London, 2005, 5, 978-1-84629-074-9,weblink 16 August 2008, no,weblink" title="web.archive.org/web/20080924152314weblink">weblink 24 September 2008, National Institute for Health and Clinical Excellence, Cognitive behavioral therapy has also been shown to reduce the number of sick days taken by people with depression, when used in conjunction with primary care.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. Research beginning in the mid-1990s suggested that CBT could perform as well as or better than antidepressants in patients with moderate to severe depression.JOURNAL, Dobson KS, A meta-analysis of the efficacy of cognitive therapy for depression, Journal of Consulting and Clinical Psychology, 57, 3, 414–19, June 1989, 2738214, 10.1037/0022-006X.57.3.414, BOOK, What Works for Whom? Second Edition: A Critical Review of Psychotherapy Research, Roth, Anthony, Fonagy, Peter, vanc, 2005, 1996, Guilford Press, 978-1-59385-272-6, 78, CBT may be effective in depressed adolescents,JOURNAL, Weersing VR, Walker PN, Review: cognitive behavioural therapy for adolescents with depression, Evidence-Based Mental Health, 11, 3, 76, August 2008, 18669678, 10.1136/ebmh.11.3.76, although its effects on severe episodes are not definitively known.JOURNAL, Harrington R, Whittaker J, Shoebridge P, Campbell F, Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder, BMJ, 316, 7144, 1559–63, May 1998, 9596592, 28555, 10.1136/bmj.316.7144.1559, Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer cognitive distortions.JOURNAL, Becker SJ, Cognitive-Behavioral Therapy for Adolescent Depression: Processes of Cognitive Change, Psychiatric Times, 25, 14, 2008,weblink CBT is particularly beneficial in preventing relapse.JOURNAL, Almeida AM, Lotufo Neto F, [Cognitive-behavioral therapy in prevention of depression relapses and recurrences: a review], Revista Brasileira de Psiquiatria, 25, 4, 239–44, October 2003, 15328551, 10.1590/S1516-44462003000400011, JOURNAL, Paykel ES, Cognitive therapy in relapse prevention in depression, The International Journal of Neuropsychopharmacology, 10, 1, 131–36, February 2007, 16787553, 10.1017/S1461145706006912, 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.

Variants

Several variants of cognitive behavior therapy have been used in those with depression, the most notable being rational emotive behavior therapy,{{Harvnb |Beck|1987|p=10}} and mindfulness-based cognitive therapy.JOURNAL, Coelho HF, Canter PH, Ernst E, Mindfulness-based cognitive therapy: evaluating current evidence and informing future research, Journal of Consulting and Clinical Psychology, 75, 6, 1000–05, December 2007, 18085916, 10.1037/0022-006X.75.6.1000, Mindfulness-based stress reduction programs may reduce depression symptoms.JOURNAL, Khoury B, Lecomte T, Fortin G, Masse M, Therien P, Bouchard V, Chapleau MA, Paquin K, Hofmann SG, Mindfulness-based therapy: a comprehensive meta-analysis, Clinical Psychology Review, 33, 6, 763–71, August 2013, 23796855, 10.1016/j.cpr.2013.05.005, JOURNAL, Jain FA, Walsh RN, Eisendrath SJ, Christensen S, Rael Cahn B, Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review, Psychosomatics, 56, 2, 140–52, 2014, 25591492, 4383597, 10.1016/j.psym.2014.10.007,weblink Mindfulness programs also appear to be a promising intervention in youth.JOURNAL, Simkin DR, Black NB, Meditation and mindfulness in clinical practice, Child and Adolescent Psychiatric Clinics of North America, 23, 3, 487–534, July 2014, 24975623, 10.1016/j.chc.2014.03.002,

Psychoanalysis

Psychoanalysis is a school of thought, founded by Sigmund Freud, which emphasizes the resolution of unconscious mental conflicts.BOOK, Dworetzky J, Psychology, Brooks/Cole Pub. Co, Pacific Grove, CA, 1997, 602, 978-0-314-20412-7, Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression.JOURNAL, Doidge N, Simon B, Lancee WJ, First M, Brunshaw J, Brauer L, Grant DC, Stevens A, Oldham JM, Mosher P, Psychoanalytic patients in the U.S., Canada, and Australia: II. A DSM-III-R validation study, Journal of the American Psychoanalytic Association, 50, 2, 615–27, 2002, 12206545, 10.1177/00030651020500021101, 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.{{Harvnb|Barlow|2005|p=20}} 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.JOURNAL, de Maat S, Dekker J, Schoevers R, van Aalst G, Gijsbers-van Wijk C, Hendriksen M, Kool S, Peen J, Van R, de Jonghe F, Short psychodynamic supportive psychotherapy, antidepressants, and their combination in the treatment of major depression: a mega-analysis based on three randomized clinical trials, Depression and Anxiety, 25, 7, 565–74, 2007, 17557313, 10.1002/da.20305,

Antidepressants

File:Zoloft bottles.jpg|thumb|SertralineSertralineConflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression.JOURNAL, Iglesias-González M, Aznar-Lou I, Gil-Girbau M, Moreno-Peral P, Peñarrubia-María MT, Rubio-Valera M, Serrano-Blanco A, Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review, Family Practice, 34, 6, 639–48, November 2017, 28985309, 10.1093/fampra/cmx054, Stronger evidence supports the usefulness of antidepressants in the treatment of depression that is chronic (dysthymia) or severe.While small benefits were found, researchers Irving Kirsch and Thomas Moore state they may be due to issues with the trials rather than a true effect of the medication.JOURNAL, The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration, Kirsch I, Moore TJ, Scoboria A, Nicholls SS, Prevention & Treatment, 2002, 5, 10.1037/1522-3736.5.1.523a, In a later publication, Kirsch concluded that the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance. Similar results were obtained in a meta-analysis by Fornier.A review commissioned by the National Institute for Health and Care Excellence (UK) concluded that there is strong evidence that selective serotonin reuptake inhibitors (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.WEB, The treatment and management of depression in adults,weblink PDF, NICE, October 2009, 12 November 2014, no,weblink" title="web.archive.org/web/20141112140520weblink">weblink 12 November 2014, 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.JOURNAL, Leucht C, Huhn M, Leucht S, Amitriptyline versus placebo for major depressive disorder, The Cochrane Database of Systematic Reviews, 12, CD009138, December 2012, 23235671, 10.1002/14651858.CD009138.pub2, Leucht, C, In 2014 the U.S. Food and Drug Administration published a systematic review of all antidepressant maintenance trials submitted to the agency between 1985 and 2012. The authors concluded that maintenance treatment reduced the risk of relapse by 52% compared to placebo, and that this effect was primarily due to recurrent depression in the placebo group rather than a drug withdrawal effect.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 50–75%, and it can take at least six to eight weeks from the start of medication to remission. Antidepressant medication treatment is usually continued for 16 to 20 weeks after remission, to minimize the chance of recurrence,JOURNAL, Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association, The American Journal of Psychiatry, 157, 4 Suppl, 1–45, April 2000, 10767867, ; Third edition {{DOI|10.1176/appi.books.9780890423363.48690}} and even up to one year of continuation is recommended.JOURNAL, Thase ME, Preventing relapse and recurrence of depression: a brief review of therapeutic options, CNS Spectrums, 11, 12 Suppl 15, 12–21, December 2006, 17146414, 10.1017/S1092852900015212, People with chronic depression may need to take medication indefinitely to avoid relapse.SSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and because they are less toxic in overdose than other antidepressants.{{Harvnb|Royal Pharmaceutical Society of Great Britain|2008|p=204}} People who do not respond to one SSRI can be switched to another antidepressant, and this results in improvement in almost 50% of cases.JOURNAL, Whooley MA, Simon GE, Managing depression in medical outpatients, The New England Journal of Medicine, 343, 26, 1942–50, December 2000, 11136266, 10.1056/NEJM200012283432607, Another option is to switch to the atypical antidepressant bupropion.JOURNAL, Zisook S, Rush AJ, Haight BR, Clines DC, Rockett CB, Use of bupropion in combination with serotonin reuptake inhibitors, Biological Psychiatry, 59, 3, 203–10, February 2006, 16165100, 10.1016/j.biopsych.2005.06.027, Venlafaxine, an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs.JOURNAL, Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC, Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents, Biological Psychiatry, 62, 11, 1217–27, December 2007, 17588546, 10.1016/j.biopsych.2007.03.027, However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits,WEB,weblink Updated prescribing advice for venlafaxine (Efexor/Efexor XL), Gordon Duff, Medicines and Healthcare products Regulatory Agency (MHRA), 31 May 2006, yes,weblink" title="web.archive.org/web/20081113133358weblink">weblink 13 November 2008, Gordon Duff, and it is specifically discouraged in children and adolescents.JOURNAL, Depression in children and young people: Identification and management in primary, community and secondary care, 2005, NHS National Institute for Health and Clinical Excellence, 12 November 2014,weblink PDF, yes,weblink" title="web.archive.org/web/20141112133741weblink">weblink 12 November 2014, JOURNAL, Mayers AG, Baldwin DS, Antidepressants and their effect on sleep, Human Psychopharmacology, 20, 8, 533–59, December 2005, 16229049, 10.1002/hup.726, For children, some research has supported the use of the SSRI antidepressant fluoxetine.JOURNAL, Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, Coghill D, Zhang Y, Hazell P, Leucht S, Cuijpers P, Pu J, Cohen D, Ravindran AV, Liu Y, Michael KD, Yang L, Liu L, Xie P, Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis, Lancet, 388, 10047, 881–90, August 2016, 27289172, 10.1016/S0140-6736(16)30385-3, The benefit however appears to be slight in children,JOURNAL, Tsapakis EM, Soldani F, Tondo L, Baldessarini RJ, Efficacy of antidepressants in juvenile depression: meta-analysis, The British Journal of Psychiatry, 193, 1, 10–17, July 2008, 18700212, 10.1192/bjp.bp.106.031088, while other antidepressants have not been shown to be effective. Medications are not recommended in children with mild disease.JOURNAL, Cheung AH, Zuckerbrot RA, Jensen PS, Laraque D, Stein RE, Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management, Pediatrics, 141, 3, e20174082, February 2018, 29483201, 10.1542/peds.2017-4082, There is also insufficient evidence to determine effectiveness in those with depression complicated by dementia.JOURNAL, Nelson JC, Devanand DP, A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia, Journal of the American Geriatrics Society, 59, 4, 577–85, April 2011, 21453380, 10.1111/j.1532-5415.2011.03355.x, Any antidepressant can cause low blood sodium levels;JOURNAL, Palmer BF, Gates JR, Lader M, Causes and management of hyponatremia, The Annals of Pharmacotherapy, 37, 11, 1694–702, November 2003, 14565794, 10.1345/aph.1D105, nevertheless, it has been reported more often with SSRIs. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating atypical antidepressant mirtazapine can be used in such cases.JOURNAL, Guaiana G, Barbui C, Hotopf M, Amitriptyline for depression, The Cochrane Database of Systematic Reviews, 18, 3, CD004186, July 2007, 17636748, 10.1002/14651858.CD004186.pub2, JOURNAL, Anderson IM, Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability, Journal of Affective Disorders, 58, 1, 19–36, April 2000, 10760555, 10.1016/S0165-0327(99)00092-0, 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.JOURNAL, Krishnan KR, Revisiting monoamine oxidase inhibitors, The Journal of Clinical Psychiatry, 68 Suppl 8, 35–41, 2007, 17640156, 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.JOURNAL, Bonnet U, Moclobemide: therapeutic use and clinical studies, CNS Drug Reviews, 9, 1, 97–140, 2003, 12595913, 10.1111/j.1527-3458.2003.tb00245.x, 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.WEB,weblink Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidality, 29 May 2008, Hammad TA, 16 August 2004, FDA, 42, 115, no,weblink" title="web.archive.org/web/20080625161255weblink">weblink 25 June 2008, JOURNAL, Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN, Newer generation antidepressants for depressive disorders in children and adolescents, The Cochrane Database of Systematic Reviews, 11, CD004851, November 2012, 23152227, 10.1002/14651858.CD004851.pub3, For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection;JOURNAL, Gunnell D, Saperia J, Ashby D, Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review, BMJ, 330, 7488, 385, February 2005, 15718537, 549105, 10.1136/bmj.330.7488.385, another an increased risk;JOURNAL, Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, Hutton B, Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials, BMJ, 330, 7488, 396, February 2005, 15718539, 549110, 10.1136/bmj.330.7488.396, and a third no risk in those 25–65 years old and a decreased risk in those more than 65.JOURNAL, Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G, Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration, BMJ, 339, b2880, August 2009, 19671933, 2725270, 10.1136/bmj.b2880, 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 patients younger than 24 years old.WEB,weblink FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications, 2 May 2007, U.S. Food and Drug Administration, FDA, 29 May 2008, no,weblink" title="web.archive.org/web/20080223195544weblink">weblink 23 February 2008, Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.REPORT, Medics and Foods Department, Ministry of Health, Labour and Welfare (Japan),weblink Pharmaceuticals and Medical Devices Safety Information, 261, PDF, Ministry of Health, Labour and Welfare (Japan), Japanese, no,weblink" title="web.archive.org/web/20110429200312weblink">weblink 29 April 2011,

Other medications

There is some evidence that omega-3 fatty acids fish oil supplements containing high levels of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) are effective in the treatment of, but not the prevention of major depression.JOURNAL, Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, Davis JM, Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression, The British Journal of Psychiatry, 209, 3, 192–201, September 2016, 27103682, 10.1192/bjp.bp.114.160242, However, a Cochrane review determined there was insufficient high quality evidence to suggest omega-3 fatty acids were effective in depression.JOURNAL, Appleton KM, Sallis HM, Perry R, Ness AR, Churchill R, Omega-3 fatty acids for depression in adults, The Cochrane Database of Systematic Reviews, 11, CD004692, November 2015, 26537796, 5321518, 10.1002/14651858.cd004692.pub4, There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient.JOURNAL, Parker GB, Brotchie H, Graham RK, Vitamin D and depression, Journal of Affective Disorders, 208, 56–61, January 2017, 27750060, 10.1016/j.jad.2016.08.082, There is some preliminary evidence that COX-2 inhibitors, such as celecoxib, have a beneficial effect on major depression.JOURNAL, Müller N, Myint AM, Schwarz MJ, Inflammatory biomarkers and depression, Neurotoxicity Research, 19, 2, 308–18, February 2011, 20658274, 10.1007/s12640-010-9210-2, Lithium appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression to nearly the same levels as the general population.JOURNAL, Cipriani A, Hawton K, Stockton S, Geddes JR, Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis, BMJ, 346, jun27 4, f3646, June 2013, 23814104, 10.1136/bmj.f3646, There is a narrow range of effective and safe dosages of lithium thus close monitoring may be needed.Nolen-Hoeksema, Susan. (2014) "Treatment of Mood Disorders". In (6th ed.) Abnormal Psychology p. 196. New York: McGraw-Hill. {{ISBN|978-0-07-803538-8}}. Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms in people who have tried multiple courses of medication.WEB, Gelenberg, Alan J., Freeman, Marlene P., Markowitz, John C, vanc, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd,weblink American Psychiatric Association (APA), 3 November 2014, Limited evidence suggests stimulants, such as amphetamine and modafinil, may be effective in the short term, or as adjuvant therapy.JOURNAL, Corp SA, Gitlin MJ, Altshuler LL, A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder, The Journal of Clinical Psychiatry, 75, 9, 1010–18, September 2014, 25295426, 10.4088/JCP.13r08851, JOURNAL, Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G, Stimulants for depression: On the up and up?, The Australian and New Zealand Journal of Psychiatry, 50, 3, 203–07, March 2016, 26906078, 10.1177/0004867416634208, Also, it is suggested that folate supplements may have a role in depression management.JOURNAL, Taylor MJ, Carney S, Geddes J, Goodwin G, Folate for depressive disorders, The Cochrane Database of Systematic Reviews, 2, CD003390, 2003, 12804463, 10.1002/14651858.CD003390, There is tentative evidence for benefit from testosterone in males.JOURNAL, Walther, A, Breidenstein, J, Miller, R, Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis., JAMA Psychiatry, 1 January 2019, 76, 1, 31–40, 10.1001/jamapsychiatry.2018.2734, 30427999,

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in patients to provide relief from psychiatric illnesses.Rudorfer, MV, Henry, ME, Sackeim, HA (2003). "Electroconvulsive therapy". In A Tasman, J Kay, JA Lieberman (eds) Psychiatry, Second Edition. Chichester: John Wiley & Sons Ltd, 1865–1901.{{rp|1880}} ECT is used with informed consentJOURNAL, Beloucif S, Informed consent for special procedures: electroconvulsive therapy and psychosurgery, Current Opinion in Anesthesiology, 26, 2, 182–85, April 2013, 23385317, 10.1097/ACO.0b013e32835e7380, as a last line of intervention for major depressive disorder.FDA. FDA Executive Summary {{webarchive|url=https://web.archive.org/web/20150924161659weblink |date=24 September 2015 }}. 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."A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar.JOURNAL, Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK, Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis, Bipolar Disorders, 14, 2, 146–50, March 2012, 22420590, 10.1111/j.1399-5618.2012.00997.x, Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.JOURNAL, Jelovac A, Kolshus E, McLoughlin DM, Relapse following successful electroconvulsive therapy for major depression: a meta-analysis, Neuropsychopharmacology, 38, 12, 2467–74, November 2013, 23774532, 3799066, 10.1038/npp.2013.149, Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anesthesia.Surgeon General (1999). Mental Health: A Report of the Surgeon General {{webarchive|url=https://web.archive.org/web/20070112012907weblink |date=12 January 2007 }}, chapter 4.{{rp|259}} Immediately following treatment, the most common adverse effects are confusion and memory loss.BOOK, American Psychiatric Association, The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging, 2nd, Washington, DC, American Psychiatric Publishing, 2001,weblink 978-0-89042-206-9, Committee on Electroconvulsive Therapy, ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.JOURNAL, Pompili M, Dominici G, Giordano G, Longo L, Serafini G, Lester D, Amore M, Girardi P, Electroconvulsive treatment during pregnancy: a systematic review, Expert Review of Neurotherapeutics, 14, 12, 1377–90, December 2014, 25346216, 10.1586/14737175.2014.972373, A usual course of ECT involves multiple administrations, typically given two or three times per week, until the patient is no longer suffering symptoms. ECT is administered under anesthesia with a muscle relaxant.WEB,weblink 5 Outdated Beliefs About ECT, Psych Central.com, no,weblink" title="web.archive.org/web/20130808042410weblink">weblink 8 August 2013, 2016-05-17, 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 patients receive maintenance ECT.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.JOURNAL, Abbott CC, Gallegos P, Rediske N, Lemke NT, Quinn DK, A review of longitudinal electroconvulsive therapy: neuroimaging investigations, Journal of Geriatric Psychiatry and Neurology, 27, 1, 33–46, March 2014, 24381234, 10.1177/0891988713516542,

Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) or deep transcranial magnetic stimulation is a noninvasive method used to stimulate small regions of the brain.WEB,weblink NiCE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine, yes,weblink" title="web.archive.org/web/20151004194631weblink">weblink 4 October 2015, TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008WEB,weblink Melkerson, MN (2008-12-16). "Special Premarket 510(k) Notification for NeuroStar® TMS Therapy System for Major Depressive Disorder" (pdf). Food and Drug Administration. Retrieved 2010-07-16, no,weblink" title="web.archive.org/web/20100331000421weblink">weblink 31 March 2010, and as of 2014 evidence supports that it is probably effective.JOURNAL, Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS), Clinical Neurophysiology, 125, 11, 2150–206, November 2014, 25034472, 10.1016/j.clinph.2014.05.021, The American Psychiatric AssociationWEB,weblink American Psychiatric Association (2010). (eds: Gelenberg, AJ, Freeman, MP, Markowitz, JC, Rosenbaum, JF, Thase, ME, Trivedi, MH, Van Rhoads, RS). Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, the Canadian Network for Mood and Anxiety Disorders,WEB,weblink Journal of Affective Disorders, 117, 2009, S1–S64, yes,weblink" title="web.archive.org/web/20150823230409weblink">weblink 23 August 2015, and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD.JOURNAL, Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG, Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial, Biological Psychiatry, 58, 5, 347–54, September 2005, 16139580, 10.1016/j.biopsych.2005.05.025,

Other

Bright light therapy reduces depression symptom severity, with benefit for both seasonal affective disorder and for nonseasonal depression, and an effect similar to those for conventional antidepressants. For nonseasonal depression, adding light therapy to the standard antidepressant treatment was not effective.JOURNAL, Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CB, The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence, The American Journal of Psychiatry, 162, 4, 656–62, April 2005, 15800134, 10.1176/appi.ajp.162.4.656, harv, For nonseasonal depression, where light was used mostly in combination with antidepressants or wake therapy, a moderate effect was found, with response better than control treatment in high-quality studies, in studies that applied morning light treatment, and with people who respond to total or partial sleep deprivation.JOURNAL, Tuunainen A, Kripke DF, Endo T, Light therapy for non-seasonal depression, The Cochrane Database of Systematic Reviews, 2, CD004050, 2004, 15106233, 10.1002/14651858.CD004050.pub2, harv, Tuunainen, Arja, Both analyses noted poor quality, short duration, and small size of most of the reviewed studies. There is insufficient evidence for ReikiJOURNAL, Joyce J, Herbison GP, Reiki for depression and anxiety, The Cochrane Database of Systematic Reviews, 4, CD006833, April 2015, 25835541, 10.1002/14651858.cd006833.pub2, and dance movement therapy in depression.JOURNAL, Meekums B, Karkou V, Nelson EA, Dance movement therapy for depression, The Cochrane Database of Systematic Reviews, 2, CD009895, February 2015, 25695871, 10.1002/14651858.cd009895.pub2,

Prognosis

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.JOURNAL, Posternak MA, Miller I, Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups, Journal of Affective Disorders, 66, 2–3, 139–46, October 2001, 11578666, 10.1016/S0165-0327(00)00304-9, The median duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.JOURNAL, Posternak MA, Solomon DA, Leon AC, Mueller TI, Shea MT, Endicott J, Keller MB, The naturalistic course of unipolar major depression in the absence of somatic therapy, The Journal of Nervous and Mental Disease, 194, 5, 324–29, May 2006, 16699380, 10.1097/01.nmd.0000217820.33841.53, Studies have shown that 80% of those suffering from their first major depressive episode will suffer from at least one more during their life,JOURNAL, Fava GA, Park SK, Sonino N, Treatment of recurrent depression, Expert Review of Neurotherapeutics, 6, 11, 1735–40, November 2006, 17144786, 10.1586/14737175.6.11.1735, with a lifetime average of 4 episodes.JOURNAL, Limosin F, Mekaoui L, Hautecouverture S, [Prophylactic treatment for recurrent major depression], Presse Médicale, 36, 11 Pt 2, 1627–33, November 2007, 17555914, 10.1016/j.lpm.2007.03.032, 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.JOURNAL, Eaton WW, Shao H, Nestadt G, Lee HB, Lee BH, Bienvenu OJ, Zandi P, Population-based study of first onset and chronicity in major depressive disorder, Archives of General Psychiatry, 65, 5, 513–20, May 2008, 18458203, 2761826, 10.1001/archpsyc.65.5.513, 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.JOURNAL, Holma KM, Holma IA, Melartin TK, Rytsälä HJ, Isometsä ET, Long-term outcome of major depressive disorder in psychiatric patients is variable, The Journal of Clinical Psychiatry, 69, 2, 196–205, February 2008, 18251627, 10.4088/JCP.v69n0205, JOURNAL, Kanai T, Takeuchi H, Furukawa TA, Yoshimura R, Imaizumi T, Kitamura T, Takahashi K, Time to recurrence after recovery from major depressive episodes and its predictors, Psychological Medicine, 33, 5, 839–45, July 2003, 12877398, 10.1017/S0033291703007827, A high proportion of people who experience full symptomatic remission still have at least one not fully resolved symptom after treatment.JOURNAL, Culpepper L, Muskin PR, Stahl SM, Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability, The American Journal of Medicine, 128, 9 Suppl, S1–S15, September 2015, 26337210, 10.1016/j.amjmed.2015.07.001, Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment. Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many randomized controlled trials indicate 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.JOURNAL, Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM, Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review, Lancet, 361, 9358, 653–61, February 2003, 12606176, 10.1016/S0140-6736(03)12599-8, People experiencing repeated episodes of depression require ongoing treatment in order to prevent more severe, long-term depression. In some cases, people must take medications for the rest of their lives.WEB,weblink Major Depression, MedlinePlus, 10 March 2014, 16 July 2010, no,weblink" title="web.archive.org/web/20100707122024weblink">weblink 7 July 2010, 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.WEB,weblink Depression, Major: Prognosis, MDGuidelines, The Guardian Life Insurance Company of America, 16 July 2010, no,weblink" title="web.archive.org/web/20100420055044weblink">weblink 20 April 2010, Depressed individuals have a shorter life expectancy than those without depression, in part because depressed patients are at risk of dying of suicide.JOURNAL, Cassano P, Fava M, Depression and public health: an overview, Journal of Psychosomatic Research, 53, 4, 849–57, October 2002, 12377293, 10.1016/S0022-3999(02)00304-5, However, they also have a higher rate of dying from other causes,JOURNAL, Rush AJ, The varied clinical presentations of major depressive disorder, The Journal of Clinical Psychiatry, 68 Suppl 8, Supplement 8, 4–10, 2007, 17640152, being more susceptible to medical conditions such as heart disease. Up to 60% 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.BOOK, Barlow DH, Durand VM, Abnormal psychology: An integrative approach (5th ed.), Thomson Wadsworth, Belmont, CA, 2005, 978-0-534-63356-1, 248–49, The lifetime risk of suicide associated with a diagnosis of major depression in the US is estimated at 3.4%, which averages two highly disparate figures of almost 7% for men and 1% for womenJOURNAL, Blair-West GW, Mellsop GW, Major depression: does a gender-based down-rating of suicide risk challenge its diagnostic validity?, The Australian and New Zealand Journal of Psychiatry, 35, 3, 322–28, June 2001, 11437805, 10.1046/j.1440-1614.2001.00895.x, (although suicide attempts are more frequent in women).JOURNAL, Oquendo MA, Bongiovi-Garcia ME, Galfalvy H, Goldberg PH, Grunebaum MF, Burke AK, Mann JJ, Sex differences in clinical predictors of suicidal acts after major depression: a prospective study, The American Journal of Psychiatry, 164, 1, 134–41, January 2007, 17202555, 3785095, 10.1176/ajp.2007.164.1.134, The estimate is substantially lower than a previously accepted figure of 15%, which had been derived from older studies of hospitalized patients.JOURNAL, Bostwick JM, Pankratz VS, Affective disorders and suicide risk: a reexamination, The American Journal of Psychiatry, 157, 12, 1925–32, December 2000, 11097952, 10.1176/appi.ajp.157.12.1925, Depression is often associated with unemployment and poverty.JOURNAL, Weich S, Lewis G, Poverty, unemployment, and common mental disorders: population based cohort study, BMJ, 317, 7151, 115–19, July 1998, 9657786, 28602, 10.1136/bmj.317.7151.115, Major depression is currently the leading cause of disease burden in North America and other high-income countries, and the fourth-leading cause worldwide. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after HIV, according to the WHO.JOURNAL, Mathers CD, Loncar D, Projections of global mortality and burden of disease from 2002 to 2030, PLoS Medicine, 3, 11, e442, November 2006, 17132052, 1664601, 10.1371/journal.pmed.0030442, Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.JOURNAL, Andrews G, Reducing the burden of depression, Canadian Journal of Psychiatry, 53, 7, 420–27, July 2008, 18674396, 10.1177/070674370805300703,

Epidemiology

File:Unipolar depressive disorders world map - DALY - WHO2004.svg|thumb|upright=1.15|weblink WHO Disease and injury country estimates, 2009, World Health Organization, 11 November 2009, no,weblink" title="web.archive.org/web/20091111101009weblink">weblink 11 November 2009, {{colbegin}}{{legend">#b3b3b3|no data}}{{legend|#ffff65|1450}}{{colend}}Major depressive disorder affects approximately 216 million people in 2015 (3% of the global population). 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. In North America, the probability of having a major depressive episode within a year-long period is 3–5% for males and 8–10% for females.JOURNAL, Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE, Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication, Archives of General Psychiatry, 62, 6, 593–602, June 2005, 15939837, 10.1001/archpsyc.62.6.593, JOURNAL, Murphy JM, Laird NM, Monson RR, Sobol AM, Leighton AH, A 40-year perspective on the prevalence of depression: the Stirling County Study, Archives of General Psychiatry, 57, 3, 209–15, March 2000, 10711905, 10.1001/archpsyc.57.3.209, 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.JOURNAL, Kuehner C, Gender differences in unipolar depression: an update of epidemiological findings and possible explanations, Acta Psychiatrica Scandinavica, 108, 3, 163–74, September 2003, 12890270, 10.1034/j.1600-0447.2003.00204.x, 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. Depression is a major cause of disability worldwide.WEB,weblink The world health report 2001 â€“ Mental Health: New Understanding, New Hope, 19 October 2008, WHO website, World Health Organization, 2001, no,weblink" title="web.archive.org/web/20081016085638weblink">weblink 16 October 2008, 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.JOURNAL, Eaton WW, Anthony JC, Gallo J, Cai G, Tien A, Romanoski A, Lyketsos C, Chen LS, Natural history of Diagnostic Interview Schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up, Archives of General Psychiatry, 54, 11, 993–99, November 1997, 9366655, 10.1001/archpsyc.1997.01830230023003, 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.JOURNAL, Rickards H, Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke, Journal of Neurology, Neurosurgery, and Psychiatry, 76 Suppl 1, i48–52, March 2005, 15718222, 1765679, 10.1136/jnnp.2004.060426, 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.JOURNAL, Alboni P, Favaron E, Paparella N, Sciammarella M, Pedaci M, Is there an association between depression and cardiovascular mortality or sudden death?, Journal of Cardiovascular Medicine, 9, 4, 356–62, April 2008, 18334889, 10.2459/JCM.0b013e3282785240, JOURNAL, Strik JJ, Honig A, Maes M, Depression and myocardial infarction: relationship between heart and mind, Progress in Neuro-Psychopharmacology & Biological Psychiatry, 25, 4, 879–92, May 2001, 11383983, 10.1016/S0278-5846(01)00150-6, Studies conflict on the prevalence of depression in the elderly, but most data suggest there is a reduction in this age group.JOURNAL, Jorm AF, Does old age reduce the risk of anxiety and depression? A review of epidemiological studies across the adult life span, Psychological Medicine, 30, 1, 11–22, January 2000, 10722172, 10.1017/S0033291799001452, 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.Gelder, M, Mayou, R and Geddes, J (2005). Psychiatry. 3rd ed. New York: Oxford. p. 105.

History

File:Hippocrates pushkin02.jpg|alt=|thumb|Diagnoses of depression go back at least as far as HippocratesHippocratesThe Ancient Greek physician Hippocrates described a syndrome of melancholia 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.Hippocrates, Aphorisms, Section 6.23 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.JOURNAL, Radden, J, 2003, Is this dame melancholy? Equating today's depression and past melancholia, Philosophy, Psychiatry, & Psychology, 10, 1, 37–52, 10.1353/ppp.2003.0081, The term depression itself was derived from the Latin verb deprimere, "to press down".depress. (n.d.). Online Etymology Dictionary. Retrieved 30 June 2008, from Dictionary.com {{webarchive|url=https://web.archive.org/web/20081203095346weblink |date=3 December 2008 }} 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.WEB, Wolpert, L, 1999, Malignant Sadness: The Anatomy of Depression, The New York Times,weblink 30 October 2008, no,weblink" title="web.archive.org/web/20090409111218weblink">weblink 9 April 2009, 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.JOURNAL, Berrios GE, Melancholia and depression during the 19th century: a conceptual history, The British Journal of Psychiatry, 153, 3, 298–304, September 1988, 3074848, 10.1192/bjp.153.3.298, Since Aristotle, melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. The newer concept abandoned these associations and through the 19th century, became more associated with women.(File:A wretched man with an approaching depression; represented b Wellcome V0011145.jpg|thumb|left|A historical caricature of a man with an approaching depression)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.JOURNAL, Davison, K, 2006, Historical aspects of mood disorders, Psychiatry, 5, 4, 115–18, 10.1383/psyt.2006.5.4.115, Sigmund 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.JOURNAL, Carhart-Harris RL, Mayberg HS, Malizia AL, Nutt D, Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry, Annals of General Psychiatry, 7, 9, July 2008, 18652673, 2515304, 10.1186/1744-859X-7-9, The patient's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness.BOOK, Richards A, Freud S, 11. On Metapsychology: The Theory of Psycholoanalysis, Mourning and Melancholia, 245–69, Pelican, Aylesbury, Bucks, 1984, 978-0-14-021740-7, He also emphasized early life experiences as a predisposing factor. 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.JOURNAL, Lewis, AJ, 1934, Melancholia: A historical review, Journal of Mental Science, 80, 328, 1–42, 10.1192/bjp.80.328.1, 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.BOOK, Diagnostic and statistical manual of mental disorders: DSM-II, American Psychiatric Association, American Psychiatric Publishing, Inc., Washington, DC, 1968, Schizophrenia,weblink PDF, 3 August 2008, 36–37, 40, 10.1176/appi.books.9780890420355.dsm-ii, 2019-05-25, In the mid-20th century, researchers theorized that depression was caused by a chemical imbalance in neurotransmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms.JOURNAL, Schildkraut JJ, The catecholamine hypothesis of affective disorders: a review of supporting evidence, The American Journal of Psychiatry, 122, 5, 509–22, November 1965, 5319766, 10.1176/ajp.122.5.509, The chemical imbalance theory has never been proven.JOURNAL, Paris J, The mistreatment of major depressive disorder, Canadian Journal of Psychiatry, 59, 3, 148–51, March 2014, 24881163, 4079242, 10.1177/070674371405900306, Review, 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.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.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),WEB, Spitzer RL, Endicott J, Robins E, 1975,weblink The development of diagnostic criteria in psychiatry, 8 November 2008, no,weblink" title="web.archive.org/web/20051214203223weblink">weblink 14 December 2005, and was incorporated into the DSM-III in 1980.JOURNAL, Philipp M, Maier W, Delmo CD, The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R, European Archives of Psychiatry and Clinical Neuroscience, 240, 4–5, 258–65, 1991, 1829000, 10.1007/BF02189537, 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.BOOK, Gruenberg, AM, Goldstein, RD, Pincus, HA, Biology of Depression, 1–12, 2005,weblink Biology of Depression: From Novel Insights to Therapeutic Strategies (eds J. Licinio and M-L Wong), Wiley-VCH Verlag GmbH, 30 October 2008, 10.1002/9783527619672.ch1, 978-3-527-61967-2, Classification of Depression: Research and Diagnostic Criteria: DSM-IV and ICD-10, 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.JOURNAL, Bolwig, Tom G, vanc, Melancholia: Beyond DSM, Beyond Neurotransmitters. Proceedings of a conference, May 2006, Copenhagen, Denmark, Acta Psychiatrica Scandinavica. Supplementum, 115, 433, 4–183, 2007, 17280564, 10.1111/j.1600-0447.2007.00956.x, JOURNAL, Fink M, Bolwig TG, Parker G, Shorter E, Melancholia: restoration in psychiatric classification recommended, Acta Psychiatrica Scandinavica, 115, 2, 89–92, February 2007, 17244171, 3712974, 10.1111/j.1600-0447.2006.00943.x, 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.BOOK, The Antidepressant Era, Healy, David, vanc, David Healy (psychiatrist), 1999, Harvard University Press, Cambridge, MA, 978-0-674-03958-2, 42,

Society and culture

File:Abraham Lincoln O-60 by Brady, 1862.jpg|thumb|The 16th American president Abraham Lincoln had "(Depression (mood)|melancholy]]", a condition that now may be referred to as clinical depression.Wolf, Joshua "Lincoln's Great Depression" {{webarchive|url=https://www.webcitation.org/62a4fProj?url=http://www.theatlantic.com/magazine/archive/2005/10/lincoln-apos-s-great-depression/4247/ |date=20 October 2011 }}, The Atlantic, October 2005, Retrieved 10 October 2009){{See also|List of people with major depressive disorder}}

Terminology

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."JOURNAL,weblink The Depression Wars: Would Honest Abe Have Written the Gettysburg Address on Prozac?, Maloney F, 3 November 2005, Slate, 3 October 2008, no,weblink" title="web.archive.org/web/20080925012423weblink">weblink 25 September 2008, There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or is 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.JOURNAL, Karasz A, Cultural differences in conceptual models of depression, Social Science & Medicine, 60, 7, 1625–35, April 2005, 15652693, 10.1016/j.socscimed.2004.08.011, JOURNAL, Tilbury F, Rapley M, 2004, 'There are orphans in Africa still looking for my hands': African women refugees and the sources of emotional distress, Health Sociology Review, 13, 1, 54–64, 10.5172/hesr.13.1.54, The diagnosis is less common in some countries, such as China. It has been argued that the Chinese traditionally deny or somatize emotional depression (although since the early 1980s, the Chinese denial of depression may have modified).JOURNAL, Parker G, Gladstone G, Chee KT, Depression in the planet's largest ethnic group: the Chinese, The American Journal of Psychiatry, 158, 6, 857–64, June 2001, 11384889, 10.1176/appi.ajp.158.6.857, Alternatively, it may be that Western cultures reframe and elevate some expressions of human distress to disorder status. Australian professor Gordon Parker and others have argued that the Western concept of depression "medicalizes" sadness or misery.JOURNAL, Parker G, Is depression overdiagnosed? Yes, BMJ, 335, 7615, 328, August 2007, 17703040, 1949440, 10.1136/bmj.39268.475799.AD, JOURNAL, Pilgrim D, Bentall R, 1999, The medicalisation of misery: A critical realist analysis of the concept of depression, Journal of Mental Health, 8, 3, 261–74, 10.1080/09638239917580, Similarly, Hungarian-American psychiatrist Thomas Szasz and others argue that depression is a metaphorical illness that is inappropriately regarded as an actual disease.WEB, Steibel W (Producer), 1998,weblink Is depression a disease?, Debatesdebates, 16 November 2008, no,weblink" title="web.archive.org/web/20081228184624weblink">weblink 28 December 2008, There has also been concern that the DSM, as well as the field of descriptive psychiatry that employs it, tends to reify abstract phenomena such as depression, which may in fact be social constructs.BOOK, Blazer DG, The age of melancholy: "Major depression" and its social origins, Routledge, New York, 2005, 978-0-415-95188-3, American archetypal psychologist James Hillman writes that depression can be healthy for the soul, insofar as "it brings refuge, limitation, focus, gravity, weight, and humble powerlessness."BOOK, Hillman J, Moore T, A blue fire: Selected writings by James Hillman, Harper & Row, New York, 1989, 152–53, 978-0-06-016132-3, Hillman argues that therapeutic attempts to eliminate depression echo the Christian theme of resurrection, but have the unfortunate effect of demonizing a soulful state of being.

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,BOOK, Seymour, Miranda, vanc, Mary Shelley, Grove Press, 2002, 560–61, 978-0-8021-3948-1, American-British writer Henry James,WEB,weblink Biography of Henry James, Public Broadcasting Service, pbs.org, 19 August 2008, yes,weblink" title="web.archive.org/web/20081008042925weblink">weblink 8 October 2008, and American president Abraham Lincoln.BOOK, Burlingame, Michael, vanc, The Inner World of Abraham Lincoln, University of Illinois Press, Urbana, 1997, 978-0-252-06667-2, xvii, 92–113, Some well-known contemporary people with possible depression include Canadian songwriter Leonard CohenWEB, Pita E,weblink An Intimate Conversation with...Leonard Cohen, 26 September 2001, 3 October 2008, no,weblink" title="web.archive.org/web/20081011082500weblink">weblink 11 October 2008, and American playwright and novelist Tennessee Williams.JOURNAL, Jeste ND, Palmer BW, Jeste DV, Tennessee Williams, The American Journal of Geriatric Psychiatry, 12, 4, 370–75, 2004, 15249274, 10.1097/00019442-200407000-00004, Some pioneering psychologists, such as Americans William JamesBOOK, James H, Letters of William James (Vols. 1 and 2), Kessinger Publishing Co, Montana, 147–48, 978-0-7661-7566-2, 1920, {{Harvnb |Hergenhahn|2005|p=311}} and John B. Watson,BOOK, Cohen D, J. B. Watson: The Founder of Behaviourism, Routledge & Kegan Paul, London, 1979, 7, 978-0-7100-0054-5, dealt with their own depression.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.JOURNAL, Andreasen NC, The relationship between creativity and mood disorders, Dialogues in Clinical Neuroscience, 10, 2, 251–5, 2008, 18689294, 3181877, JOURNAL, Simonton DK, 2005, Are genius and madness related? Contemporary answers to an ancient question, Psychiatric Times, 22, 7,weblink no,weblink" title="web.archive.org/web/20090114065333weblink">weblink 14 January 2009, British literature gives many examples of reflections on depression.BOOK, Heffernan CF, The melancholy muse: Chaucer, Shakespeare and early medicine, Duquesne University Press, Pittsburgh, 1996, 978-0-8207-0262-9, 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."BOOK,weblink Autobiography, Mill JS, txt, Project Gutenberg EBook, 1826–32, A crisis in my mental history: One stage onward, 9 August 2008, 978-1-4212-4200-2, 2003, no,weblink" title="web.archive.org/web/20080921084533weblink">weblink 21 September 2008, John Stuart Mill, JOURNAL, Sterba R, The 'Mental Crisis' of John Stuart Mill, Psychoanalytic Quarterly, 16, 2, 271–72, 1947,weblink 5 November 2008, no,weblink" title="web.archive.org/web/20090112164603weblink">weblink 12 January 2009, English writer Samuel Johnson used the term "the black dog" in the 1780s to describe his own depression,WEB,weblink Churchill's Black Dog?: The History of the 'Black Dog' as a Metaphor for Depression, 2005, 18 August 2008, Black Dog Institute website, Black Dog Institute, yes,weblink" title="web.archive.org/web/20080910170230weblink">weblink 10 September 2008, and it was subsequently popularized by depression sufferer former British Prime Minister Sir Winston Churchill.Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on treatment differ markedly to those of health professionals; alternative treatments are held to be more helpful than pharmacological ones, which are viewed poorly.BOOK, Unmet Need in Psychiatry:Problems, Resources, Responses, Andrews G, Henderson S, 2000, Cambridge University Press, 409, Public knowledge of and attitudes to mental disorders: a limiting factor in the optimal use of treatment services, Jorm AF, Angermeyer M, Katschnig H, 978-0-521-66229-1, 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;JOURNAL, Paykel ES, Tylee A, Wright A, Priest RG, Rix S, Hart D, The Defeat Depression Campaign: psychiatry in the public arena, The American Journal of Psychiatry, 154, 6 Suppl, 59–65, June 1997, 9167546, 10.1176/ajp.154.6.59, a MORI study conducted afterwards showed a small positive change in public attitudes to depression and treatment.JOURNAL, Paykel ES, Hart D, Priest RG, Changes in public attitudes to depression during the Defeat Depression Campaign, The British Journal of Psychiatry, 173, 6, 519–22, December 1998, 9926082, 10.1192/bjp.173.6.519,

Elderly

{{See also|Late life depression}}{{anchor|Geriatric|Geriatrics}}Depression is especially common among those over 65 years of age and increases in frequency beyond this age.WEB,weblink Depression treatment for the elderly, Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU), www.sbu.se, 16 June 2016, no,weblink" title="web.archive.org/web/20160618011954weblink">weblink 18 June 2016, 2015-01-27, In addition, the risk of depression increases in relation to the frailty of the individual. Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly. Both symptoms and treatment among the elderly differ from those of the rest of the population.As with many other diseases, it is common among the elderly not to present with classical depressive symptoms. 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. Treatment differs in that studies of SSRIs have shown lesser and often inadequate effects among the elderly, while other drugs, such as duloxetine (a serotonin-norepinephrine reuptake inhibitor), with more clear effects have adverse effects, such as dizziness, dryness of the mouth, diarrhea and constipation, which can be especially difficult to handle among the elderly.Problem solving therapy was, as of 2015, the only psychological therapy with proven effect, and can be likened to a simpler form of cognitive behavioral therapy. However, elderly with depression are seldom offered any psychological treatment, and the evidence proving other treatments effective is incomplete. ECT has been used in the elderly, and register-studies suggest it is effective, although less so as compared to the rest of the population. The risks involved with treatment of depression among the elderly as opposed to benefits are not entirely clear.

Research

MRI scans of patients with depression have revealed a number of differences in brain structure compared to those who are not depressed. Meta-analyses of neuroimaging studies in major depression reported that, compared to controls, depressed patients had increased volume of the lateral ventricles and adrenal gland and smaller volumes of the basal ganglia, thalamus, hippocampus, and frontal lobe (including the orbitofrontal cortex and gyrus rectus).JOURNAL, Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC, Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder, Archives of General Psychiatry, 68, 7, 675–690, 2011, 21727252, 10.1001/archgenpsychiatry.2011.60, see also MRI database at www.depressiondatabase.org {{webarchive|url=https://web.archive.org/web/20110929165423weblink |date=29 September 2011 }}JOURNAL, Arnone D, McIntosh AM, Ebmeier KP, Munafò MR, Anderson IM, Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses, European Neuropsychopharmacology, 22, 1, 1–16, 2012, 21723712, 10.1016/j.euroneuro.2011.05.003, Hyperintensities have been associated with patients with a late age of onset, and have led to the development of the theory of vascular depression.JOURNAL, Herrmann LL, Le Masurier M, Ebmeier KP, White matter hyperintensities in late life depression: a systematic review, Journal of Neurology, Neurosurgery, and Psychiatry, 79, 6, 619–624, 2008, 17717021, 10.1136/jnnp.2007.124651, Trials are looking at the effects of botulinum toxins on depression. The idea is that the drug is used to make the person look less frowning and that this stops the negative facial feedback from the face.JOURNAL, Kruger TH, Wollmer MA, Depression—An emerging indication for botulinum toxin treatment, Toxicon, 107, Pt A, 154–157, 2015, 26415901, 10.1016/j.toxicon.2015.09.035, In 2015 results showed, however, that the partly positive effects that had been observed until then could have been due to placebo effects.JOURNAL, Milev R, Response of depression to botulinum toxin treatment: agitation as a predictor, Frontiers in Psychiatry, 6, 55, 2015, 25941497, 4403301, 10.3389/fpsyt.2015.00055, .In 2018, the US Food and Drug Administration (FDA) approved a Phase 2 study on psilocybin in the treatment of treatment-resistant depression and granted Breakthrough Therapy Designation.WEB,weblink COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression – COMPASS, en-US, 2019-04-11,

Animals models

{{further|Animal psychopathology#Depression}}{{See|Animal models of depression}}Models of depression in animals for the purpose of study include iatrogenic depression models (such as drug-induced), forced swim tests, tail suspension test, and learned helplessness models. Criteria frequently used to assess depression in animals include expression of despair, neurovegetative changes, and anhedonia, as many other criteria for depression are untestable in animals, such as guilt and suicidality.BOOK, Krishnan V, Nestler EJ, 7, 121–47, 2011, 21225412, 3270071, 10.1007/7854_2010_108, 978-3-642-19702-4, Current Topics in Behavioral Neurosciences, Molecular and Functional Models in Neuropsychiatry, Animal Models of Depression: Molecular Perspectives,

References

{{Reflist}}

Cited works

  • BOOK, Diagnostic and statistical manual of mental disorders, Fourth Edition, Text Revision: DSM-IV-TR, American Psychiatric Publishing, Inc., Washington, DC, 2000a, 978-0-89042-025-6, CITEREFAmerican_Psychiatric_Association2000a, American Psychiatric Association,
  • BOOK, Barlow DH, Durand VM, Abnormal psychology: An integrative approach (5th ed.), Thomson Wadsworth, Belmont, CA, 2005, 978-0-534-63356-1, CITEREFBarlow2005,
  • BOOK, Beck AT, Rush J, Shaw BF, Emery G, Cognitive Therapy of depression, Guilford Press, New York, 1987, 1979, 978-0-89862-919-4, CITEREFBeck1987,
  • BOOK, Hergenhahn BR, An Introduction to the History of Psychology, 5th, Thomson Wadsworth, Belmont, CA, 2005, 978-0-534-55401-9, CITEREFHergenhahn2005,
  • BOOK, May R, The discovery of being: Writings in existential psychology, W. W. Norton & Company, New York, 1994, 978-0-393-31240-9, CITEREFMay1994,
  • BOOK, Hadzi-Pavlovic, Dusan, Parker, Gordon, vanc, Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review, Cambridge University Press, Cambridge, 1996, 978-0-521-47275-3, CITEREFParker1996,
  • BOOK, British National Formulary (BNF 56), Royal Pharmaceutical Society of Great Britain, 2008, BMJ Group and RPS Publishing, UK, 978-0-85369-778-7,weblink CITEREFRoyal_Pharmaceutical_Society_of_Great_Britain2008,
  • BOOK, Sadock, Virginia A, Sadock, Benjamin J, Kaplan, Harold I, vanc, Kaplan & Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry, Lippincott Williams & Wilkins, Philadelphia, 2003, 978-0-7817-3183-6, CITEREFSadock2002,

External links

{{Medical condition classification and resources|DiseasesDB=3589F30}}, {{ICD1033f|30}}296.2}}, {{ICD9|296.3}}|ICDO=|OMIM=608516|MedlinePlus=003213|eMedicineSubj=med|eMedicineTopic=532|MeshID=D003865}}{{Spoken Wikipedia|Mdd2 003.ogg|2014-10-06}}
  • {{dmoz|Health/Mental_Health/Disorders/Mood/Depression|Depression}}
{{Mental and behavioural disorders|selected=mood}}{{Mood disorders}}{{Featured article}}{{Authority control}}

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