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- Main article: Clinical depression
Major depressive episodes often resolve over time whether they are treated or not. Outpatients on a waiting list show a 10–15% reduction in symptoms over a few months, and around 20% will no longer meet full criteria. The median duration of an episode has been estimated at least 23 weeks, with the highest rate of recovery in the first three months.
General population studies indicate around half those who have a major depressive episode (whether treated or not) recover and remain well, while 35% will have at least one more, and around 15% experience chronic recurrence. 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.
Recurrence 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 indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use. 
Depressed individuals have a shorter life expectancy than those without depression. Although depressed patients are at risk of dying by suicide, they are also more susceptible to medical conditions such as heart disease. Up to 60% of people who commit 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. Depressed people also have a higher rate of dying from other causes. 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 women (although suicide attempts are more frequent in women). The estimate is substantially lower than a previously accepted figure of 15% which had been derived from older studies of hospitalized patients.
Once an episode of depression occurs, there is at least a 50% chance of recurrence during an individual's lifetime. Odds of recurrence increase up to 90% in individuals who have had several bouts of depression. Up to one-third of depressive episodes can become chronic
The effectiveness of treatment often depends on factors such as the amount of optimism and hope the sufferer is able to maintain, the control s/he has over stressors, the severity of symptoms, the amount of time the sufferer has been depressed, the results of previous treatments, and the degree of support of family, friends, and significant others.
Although treatment is generally effective, in some cases the condition does not respond. Treatment-resistant depression warrants a full assessment, which may lead to the addition of psychotherapy, higher medication dosages, changes of medication or combination therapy, a trial of ECT/electroshock, or even a change in the diagnosis, with subsequent treatment changes. Although this process helps many, some people's symptoms continue unabated.
Relapse is more likely if treatment has not resulted in full remission of symptoms.4 In fact, current guidelines for antidepressant use recommend 4 to 6 months of continuing treatment after symptom resolution to prevent relapse.
Combined evidence from many randomized controlled trials indicates that continuing antidepressant medications after recovery substantially reduces (halves) the chances of relapse. This preventive effect probably lasts for at least the first 36 months of use.
Anecdotal evidence suggests that chronic disease is accompanied by relapses after prolonged treatment with antidepressants (Tachyphylaxis). Psychiatric texts suggest that physicians respond to relapses by increasing dosage, complementing the medication with a different class, or changing the medication class entirely. The reason for relapse in these cases is as poorly understood as the change in brain physiology induced by the medications themselves. Possible reasons may include aging of the brain or worsening of the condition. Most SSRI psychiatric medications were developed for short-term use (a year or less) but are widely prescribed for indefinite periods. \
- ↑ Country reports and charts available. WHO website - Mental health. World Health Organization. URL accessed on 2008-09-16.
- ↑ Posternak MA, Miller I (2001). 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.
- ↑ Posternak MA, Solomon DA, Leon AC, et al. (2006). The naturalistic course of unipolar major depression in the absence of somatic therapy. Journal of Nervous and Mental Disease 194 (5): 324–29.
- ↑ Eaton WW, Shao H, Nestadt G, et al. (May 2008). Population-based study of first onset and chronicity in major depressive disorder. Archives of General Psychiatry 65 (5): 513–20.
- ↑ Holma KM, Holma IA, Melartin TK, et al. (February 2008). Long-term outcome of major depressive disorder in psychiatric patients is variable. Journal of Clinical Psychiatry 69 (2): 196–205.
- ↑ Kanai T, Takeuchi H, Furukawa TA, et al. (July 2003). Time to recurrence after recovery from major depressive episodes and its predictors. Psychological Medicine 33 (5): 839–45.
- ↑ Geddes JR, Carney SM, Davies C, et al. (February 2003). Relapse prevention with antidepressant drug treatment in depressive disorders: A systematic review. Lancet 361 (9358): 653–61.
- ↑ Cassano P, Fava M (October 2002). Depression and public health: an overview. J Psychosom Res 53 (4): 849–57.
- ↑ Cite error: Invalid
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- ↑ Barlow 2005, pp. 248–49
- ↑ Rush AJ (2007). The varied clinical presentations of major depressive disorder. The Journal of clinical psychiatry 68 (Supplement 8): 4–10.
- ↑ Blair-West GW, Mellsop GW (2001). Major depression: Does a gender-based down-rating of suicide risk challenge its diagnostic validity?. Australian and New Zealand Journal of Psychiatry 35 (3): 322–28.
- ↑ Oquendo MA, Bongiovi-Garcia ME, Galfalvy H, et al (January 2007). Sex differences in clinical predictors of suicidal acts after major depression: a prospective study. The American journal of psychiatry 164 (1): 134–41.
- ↑ Bostwick, JM, Pankratz VS (2000). Affective disorders and suicide risk: A reexamination. American Journal of Psychiatry 157 (12): 1925–32.
- ↑ Geddes, JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM (22 February 2003). Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 361 (9358): 653�61. PMID 12606176.