Major Depressive Disorder

Clinical Features and Course

Major depressive disorder may begin at any age, although it usually begins in the mid-20s and 30s. Symptoms develop over days to weeks. Some people have only a single episode, with a full return to premorbid functioning. However, more than 50 percent of those who initially suffer a single major depressive episode eventually develop another. In these cases, diagnosis is revised to recurrent major depressive disorder.

Individuals with recurrent major depressive disorder are at grater risk of developing bipolar disorder than are those with single episodes, and they are more likely to have first-degree biologic relatives with major depressive disorder. Some patients who meet the criteria for major depressive disorder, especially of the recurrent type, have a genotype that groups them more clearly with patients with bipolar disorder, as evidenced by a family history of bipolar disorder.

The early onset of their major depressive disorder, a higher frequency of depressive episodes, and a greater tendency to show psychomotor retardation and hypersomnia during the episode of major depression. These patients may have a greater tendency to develop hypomania with standard tricyclic antidepressants (TCAs), and their recurrent depressive episodes may be more responsive to lithium alone.The course of recurrent of major depressive disorder is variable. In some patients, the episodes are separated by many symptom-free years of normal functioning. For others, the episodes become increasingly frequent with greater age. Major depressive episodes nearly always reduce social, occupational, and interpersonal functioning to some degree, but functioning usually returns to the premorbid level between episodes if the episodes remit completely.

Studies of patients with major depressive disorder have found those most untreated episodes last 6 to 24 months. Two thirds of cases, symptoms remit completely and functioning returns to the premorbid level. In the remaining one-third cases, the full episode may persist for more than 2 years (about 5 to 10 percent), or recovery between episodes may be partial (about 20 to 25 percent).

Approximately one-fourth of patients develops major depression superimposed on a low-grade chronic depression (dysthymia disorder), which accounts for the majority of those with poor interepisode recovery. Major depressive episodes may end completely or only partially. If partial recovery occurs, clinical experience and some research data suggest that :

Epidemiology of Major Depressive Disorder

The point prevalence for major depressive disorder in the western industrialized nations is 2.3 to 3.2 percent for men and 4.5 to 9.3 percent for women. The lifetime risk for major depressive disorder is 7 to 12 percent for men and 20 to 25 percent for women.

Risk factors for major depressive disorder include female gender (especially during the postpartum period), a history of depressive illness in first-degree relatives, and prior episodes of major depression. The above gender difference is found in community samples and, is not due to increased female help-seeking behavior.

Prevalence rates for major depressive disorder are unrelated to race, education, income, or civil status. Recent epidemiological data clearly indicate that the age at onset of major depressive disorder has decreased for the more recently born (the "birth cohort" effect) in many cultures.

A recent available studies strongly suggests, that psychosocial events or stresses may play a significant role in precipitating the first or second episodes of major depressive disorder, but they may play little or no role in the onset of subsequent episodes.

That is, for the recurrent forms of major depressive disorder, new episodes are less likely to involve a specific precipitant as the disorder becomes more firmly established. Individuals with major depressive disorder and those with dysthymia disorder are high users of medical services and are as functionally impaired as are patients with severe chronic medical disorders.

The lifetime psychiatric co-morbidity rate for major depressive disorder can be as high as 43 percent. That is up to 43 percent of patients with major depressive disorder have history of one or more non affective psychiatric disorders. The 1-month point prevalence for concurrent in contrast to lifetime psychiatric co-morbidity is 8 percent. Depressive conditions are highly prevalent in community level of settings. The point prevalence of major depressive disorder in community care outpatient settings ranged from 4.8 to 8.6 percent; whereas 14.6 percent of adult medical inpatients studied met criteria for major depressive disorder.

Costs of Untreated Major Depressive Disorder

Patients with major depressive disorder have substantial amounts of physical and psychological disability and occupational difficulties. Untreated major depressive disorder has a substantial effect on health and functioning. Patients in a major depressive episode report substantially poorer intimate relationships and less satisfying social interactions than do members of the general population who have previously suffered from depression or who currently have other psychiatric disorders.

Physical complaints are also common during a major depressive episode. Twenty-three percent of patients in one study reported some days in which their health kept them in bed all or most of the day, in the previous 2 weeks, compared to 5 percent for the general population. The health status of community respondents with major depressive disorder, 48 per cent of who described their health as either fair of poor, compared to only 19 per cent of the general population.

Other general population data indicate that patients with major depressive disorder reported 11 disability days per 90-day interval versus 2.2 disability days for the general population. Data from community respondents indicate that 38 percent of patients with major depressive disorder have some chronic activity restriction, and 30 percent of those with depression- reported decreased activity days in the previous 2 weeks.

Clinical samples of patients with major depressive disorder also provide evidence of severe impairment in interpersonal and occupational functioning, including loss of work time. Patients with major depressive disorder have more physical illnesses than do other patients seen by doctors in primary care settings.

Health care utilization is increased in persons in the community with major depressive disorder compared to other patients in the general medical setting. Major depressive disorder is associated with increased mortality, which is generally considered to be secondary to suicide and accident.

A recent report indicated that patients with major depressive disorder admitted to nursing homes had a 59 percent greater likelihood of death in the first year following admission compared to those without major depressive disorder. Patients with major depressive disorder in a study of aged 55 and over, had a mortality rate over four times higher than that of nondepressed age-matched controls. Up to 15 percent of patients with major depressive disorder severe enough to require suicide.

Subgroups of Major Depressive Disorder

Studies of major depressive disorder reveal heterogeneity with regard to the biology, family history, pharmacological response, genetics and course of illness. The common subgroups and possible clinical relevance of each are shown in.

Major Depressive Disorders

Sub-group based on cross sectional symptoms

Sub-group based on course & time of life

Sub-group based on aetiology and symptoms

These subtypes are not all-inclusive. For example, a large number of patients, who have major depressive disorder without melancholic. psychotic, or atypical features have episodes that are not seasonally related and do not have a postpartum onset.

Three subgroups based on cross-sectional symptom features psychotic, melancholic, and atypical may have implications for treatment selection. Two based on course features; seasonal pattern and postpartum onset have prognostic utility. The seasonal type may also suggest the specific therapeutic option of light therapy.

However, these subgroups may not be etiologically distinct. Rather, they may represent varying clinical expressions of the same condition over time, in different age groups, or in the context of particular provoking stimuli.

Psychotic Features

Psychotic features refer to the presence of delusions or hallucinations. They occur in 15% of patients with major depressive disorders. In psychotic depressions, psychotic features are never present without concurrent mood symptoms. Psychotic depressions must be distinguished from schizoaffective disorder. In the Schizoaffective disorder there are periods of at least 2 weeks during which delusions or hallucinations are present without mood disturbances.

The content of the hallucinations or delusions in psychotic depressions is usually logically consistent with the predominant sad mood (mood-congruent). For example, there may be a delusion that the patient has sinned in an unforgivable way. Less commonly, the hallucinations or delusions have no obvious relationship to sadness (mood-incongruent); for example, there may be persecutory delusions, for which the person has no explanation.

Studies suggest that mood-incongruent symptoms are associated with a worse prognosis; involve into Schizophrenifrom or Schizoaffective disorders; involve a less episodic, more chronic course; and require more insidious, longer maintenance treatment.

The psychotic features of psychotic major depressive disorder usually recur in subsequent episodes, should such episodes occur. Some studies suggest that psychotic depressive episodes are familial. For psychotic depressions, TCAs plus a neuroleptic or electroconvulsive therapy (ECT) is each superior to TCAs alone in treating the illness. Given the markedly disabling nature of psychotic depression, maintenance treatments are strongly indicated when the disorder is recurrent.

However, the relative efficacy of maintenance treatment compared to placebo; the value of including both a neuroleptic and an antidepressant in maintenance phase efficacy of non-TCA medications, lithium, or selected anticonvulsant have not been studied.

Melancholic Features

The key melancholic features of major depressive disorder are :

Melancholic symptom features appear to repeat from episode in individuals with recurrent, severe major depressive disorder. They are more commonly present in older depressed patients. Melancholic features are not uniquely associated with a family history of depression. They are associated with reduced rapid eye movement latency and/or Dexamethosone nonsuppression.

Severely symptomatic patients whose depression has melancholic features are likely to respond to treatment with TCAs or to ECT. Melancholic features do not predict which antidepressants will be effective, though their presence indicates that anxiolytics will not be effective The presence of meiancholic symptom features, especially in the severely ill, should sharply increase the doctor's tendency to treat with antidepressants and should provoke a thorough questioning for the presence of psychotic symptom and features. If medications fail, ECT should be strongly considered for these patients.

Atypical Features

The groups studying atypical features define the featured differently. The atypical features may be grouped into two types, vegetative and anxious.

Vegetatiue features include :

Anxious features include :

Atypical features of either types are associated with a younger age at onset of illness. Whether these symptoms run in families, repeat across episodes. or are associated with an identifiable or unique biology is not known. However, rapid eye movement latency is not characteristically reduced in this type of mood disorder.

The relationship between atypical and melancholic symptom features remains to be clarified. Some data suggest that atypical symptoms may be more likely earlier in the course of major depressive disorder, while melancholic features are more likely to appear later.

Several studies shows that when a typical features (those in the vegetative group above) are present, monoamine oxidase inhibitors (MAOIs) are more effective than TCAs, although the latter are still more effective than placebo. Case reports and clinical experience suggest that those depressions with a typical features may respond better to selective serotonin reuptake inhibitors (SSRIs) than to TCAs.

Seasonal Pattern

DSM-IV indicates that a seasonal pattern for major depressive disorder can be diagnosed only if :

The first systematic evidence of the prevalence of seasonal affective disorder was between 2-10%. Preliminary evidence suggests that light therapy is effective in the short-term treatment of outpatients with mild to moderate seasonal major depressive disorder. Clinical reports suggest that medications may also be effective for some seasonal mood disorders in addition to light therapy.

Postpartum Onset

Postpartum mood symptoms are divided into three categories, based on severity:

Postpartum blues are brief episodes (1 to 4 days) of labile mood & tearfulness that normally occur in 50 to 80 percent of women within 1 to 5 days of delivery. Treatment consists of reassurance and time to resolve this normal response.

Postpartum psychoses can be divided into depressed and manic types. Patients with the depressed type show more psychotics, disoriented, agitated. and emotionally labile features as well as more psychomotor retardation, than do non-postpartum matched depressed controls. Most of these cases are associated with signs of organic impairment. Features of the manic type are similar to features of a classic mania. The incidence of postpartum ps4chosa is low (0.5 to 2.0 per 1,000 deliveries). Many early cases were mistaken for toxic/infectious states.

The symptoms of postpartum psychosis develop rapidly (over 24 to 72 hours), typically beginning 2 to 3 days after delivery. The period of risk for developing postpartum psychosis is within the first month following delivery.

For acute postpartum psychosis, the prognosis is generally good. However, many patients have previously had or subsequently develop a bipolar disorder. The risk of postpartum psychosis is higher for those with episodes at prior deliveries. The recurrence rate is from 33 to 51 percent.

Non Psychotic postpartum depressions (major or minor depressive disorders) have also been identified these conditions may occur from 2 weeks to 12 months postpartum, but typically occur within 6 months. The prevalence of nonpsychotic depressions is 10 to 15 percent within the first 3 to 6 months after childbirth, which is somewhat higher than are the rates (5 to 7 percent) in nonchildbearing females. However. the risk for nonpsychotic postpartum depression is higher for persons with a psychiatric history.

Clinical experience suggests that prophylactic lithium be given as soon as possible after delivery to prevent postpartum precipitation in-patients with a history of bipolar disorder. Likewise. given the high likelihood of recurrence, other previously effective psychotropic medications should be considered in those with a history of psychotic postpartum mood episodes immediately after giving birth.

The author is Director, National Institute of Mental Health.

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