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Chapter: Essentials of Psychiatry: Mood Disorders: Depression

Depression: Course and Natural History

Clinical Course and Age of Onset, Natural History of Episodes

Course and Natural History


Clinical Course and Age of Onset


In order to document onset of depressive phases as well as periods of remission, psychiatrists must pay careful attention to clinical course. Improvements in assessment procedures, including struc-tured interview guides for the assessment of depression as well as rating scales for depression, will promote better attention to course and natural history of MDD. Long-term studies of depression must incorporate information on recovery, recurrence and chronicity. The mean age of onset of major depression is 27 years of age, al-though an individual can experience the onset of MDD at any age.


Natural History of Episodes


New symptoms of MDD often develop over several to several weeks. Early manifestations of an episode of MDD include anxi-ety, sleeplessness, worry and rumination prior to the experience of overt depression. Over a lifetime, the presence of one major depressive episode is associated with a 50% chance of a recurrent episode. A history of two episodes is associated with a 70 to 80% risk of a future episode. Three or more episodes are associated with extremely high rates of recurrence. Because the majority of cases of MDD recur, continuation treatment and ongoing edu-cation regarding warning signs of relapse or recurrence are es-sential in ongoing clinical care. In an MDD when single episode recurs, a change in diagnosis to MDD recurrent is necessitated.


In comparison to individuals who develop a single episode (many of whom return to premorbid functioning), individuals with recurrent episodes of depression are at greater risk to mani-fest bipolar disorder. Individuals who experience several recur-rent episodes of depression may develop a hypomanic or manic episode requiring rediagnosis to bipolar disorder. In children and adolescents, the transformation of a diagnosis of depression to a diagnosis of bipolar disorder is higher. Approximately 40% of adolescents who are depressed, evolve a bipolar course. Because bipolar disorder is initiated with a depressive episode in four of five cases, it is important to identify those patients who are most likely to develop a bipolar disorder. Therefore, the clinician is confronted with significant diagnostic and treatment challenges when called upon to evaluate a patient, particularly an adoles-cent, who presents with depression and has no previous history of mania. Several risk factors have been identified, which predict when a first episode of MDD will evolve into bipolar disorder: 1) the first episode of depression emerges during adolescence; 2) the depression is severe and includes psychotic features; 3) psy-chomotor retardation and hypersomnia are present; 4) a family history of bipolar disorder exists, particularly across two to three generations; and 5) the patient experiences hypomania induced by antidepressant medication.


Recurrent MDD requires longitudinal observation because of its highly variable course. Generally, complete remission of an episode of MDD heralds a return to premorbid levels of social, occupational and interpersonal functioning. Therefore, the goal of treatment is a focus on achieving full remission of depressive symptoms and recovery. Untreated episodes of depression last 6 to 24 months. Symptom remission and a return to premorbid level of functioning characterize approximately 66% of depressed pa-tients. By comparison, roughly 5 to 10% of patients continue to experience a full episode of depression for greater than 2 years and approximately 20 to 25% of patients experience partial recovery between episodes. Furthermore, 25% of patients manifest “double depression”, characterized by the development of MDD superim-posed upon a mild, chronic depression (DD). Patients with double depression often demonstrate poor interepisode recovery. Four characteristics are seen in a partial remission of an episode: 1) in-creased likelihood of a subsequent episode; 2) partial interepisode recovery following subsequent episodes; 3) longer-term treatment may be required; and 4) treatment with a combination of pharma-cotherapy and psychotherapy may be indicated.


Follow-up naturalistic studies have indicated that 40.3% of individuals with MDD carry the same diagnosis 1 year later, 2.6% evidence DD, 16.7% manifest incomplete recovery and 40.5% do not meet criteria for MDD. Keller and colleagues (1992) highlight the potential for chronicity in MDD. A 5-year follow-up study indicated that 50% of 431 patients showed recovery by 6 months but 12% of the sample continued to be depressed for the entire 5-year period. The authors noted that inadequate treatment may have contributed to chronicity.

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