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Outpatient Management of Depression
2 - Why Identify and Treat Major Depression

The number of people in the United States with major depression is estimated to be between 5% and 11% of the total population.4,61,98 Over half of these individuals will have recurrent episodes periodically throughout their lives (Table 2.1). In terms of the associated mortality, morbidity, and societal costs, the impact of clinical depression is astounding (Table 2.2).

The cost to American society of depressive disorders is estimated to be $26 billion annually. This estimate does not include the effect of depression on the family.

Forty thousand to 50,000 Americans die annually because of suicide (Table 2.3). Suicide is the seventh leading cause of death in the United States. Of patients with untreated recurrent major depression, 15% will die of suicide. In up to 70% of these cases, clinical depression will be the proximal cause of death. These figures place clinical depression in the same league as leukemia as a cause of death in the United States. Suicide is the third leading cause of death among teenagers and young adults. Suicide also has an impact on the lives of the relatives, friends, and coworkers of the suicide victim. Deaths also occur as a result of accidents caused by the impaired concentration and attention characteristic of major depression.

Having major depression also increases the risk of alcohol abuse and cigarette smoking. These conditions in turn increase health problems.

TABLE 2.1 Unipolar Depression in the United States
  • High rate of occurrence:
         5% to 11% lifetime prevalence
         10 to 14 million in the United States depressed          in any year25
  • Episodes can be of long duration (years)
  • 50% rate of recurrence following a single episode; higher if patient has had multiple episodes or a positive family history
  • Morbidity comparable to angina and advanced coronary artery disease
  • High mortality from suicide if untreated
TABLE 2.2 The Hidden Cost of Not Treating Major Depression


  • 30,000 to 35,000 suicides per year103
  • Fatal accidents due to impaired concentration and attention
  • Death due to illnesses which can be a sequelae (eg, alcohol abuse)

Patient Morbidity

  • Suicide attempts
  • Accidents
  • Resultant illnesses
  • Lost jobs
  • Failure to advance in career and school
  • Substance abuse

Societal Costs

  • Dysfunctional families
  • Absenteeism
  • Decreased productivity
  • Job-related injuries
  • Adverse effect on quality control in the workplace
TABLE 2.3 Suicide and Major Depression: The Rule of Seven
  • One out of seven people with recurrent depressive illness commit suicide72
  • Seventy percent of suicides have depressive illness206
  • Seventy percent of suicides see their primary-care practitioner within 6 weeks of suicide207
  • Suicide is the seventh leading cause of death in the United States103


Patients with major depression frequently self-medicate with alcohol to help themselves sleep and/or to reduce associated anxiety. Tragically, alcohol provides only fleeting relief and then aggravates the underlying biochemistry of clinical depression, setting up the potential for a downward, vicious spiral.

The incidence of cigarette smoking is higher in depressed individuals and may be a harder habit to break in this population. In a prospective study of almost 3,000 patients, depression was found to be associated with a 5 times greater number of disability days in employed individuals. Other studies have found depression to be associated with:

  • Poorer physical health
  • Increased health-care utilization.

Based on a 15-year prospective outcome study, 80% of depressed individuals who are not treated will have a poor outcome, either remaining ill or experiencing recurrence(s) of their illness. The disability due to major depression is on par with or worse than that of chronic medical illnesses such as coronary artery disease, hypertension, diabetes mellitus, and arthritis, adversely affecting:

  • Health-care utilization
  • Absenteeism at work
  • Productivity
  • Job-related injuries
  • Quality control in the workplace due to impaired concentration and attention.

To fully appreciate the impact of depression, the following would also have to be quantified:

  • The cost of decreased work productivity by depressed individuals suffering functional impairment due to major depression
  • The impact on the individual and their family of:
    - Failure to advance in one's education
    - Failure to advance in one's career
    - Lost jobs
    - Marital strife
    - Family dysfunction.

Major depression (Table 2.4):

  • Is twice as likely to occur in women
  • Has a peak age of onset from 20 to 40 years of age
  • Runs in families-if there is a family history of major depression, a person has a three-fold higher likelihood of developing this disorder in comparison to the general population
  • Has a greater incidence among separated and divorced people (which is cause versus which is effect is not known, since major depression may cause separation and divorce)
  • Is more likely to be reported in unmarried than married men (again, the causal relationship is unclear)
  • Is more likely to be reported in married than unmarried women (again, the causal relationship is unknown since depressed women with chronic low self-esteem may settle for abusive and dysfunctional mates)
  • Has an increased risk of occurrence for women during the last trimester, the first 6 months following childbirth, and during the onset of menopause as well as an increase in symptoms prior to menses (suggesting a possible role for fluctuations in sex hormones as pathophysiologically important "triggers" for the expression of the illness). Of interest, neuronal systems (norepinephrine and serotonin) that have been implicated in the pathophysiology of the illness are influenced by fluctuations in estrogen levels.
TABLE 2.4 Risk Factors for Major Depression
Risk Factor Association
Gender Major depression is twice as likely in women
Age Peak age of onset is 20 to 40 years of age
Family history 3 times higher risk with positive history
Marital status Separated and divorced persons report higher rates
Married males lower rates than unmarried males
Married females higher rates than unmarried females
Postpartum An increased risk for the 6-month period following childbirth
Negative life events Possible association
Early parental death Possible association

Women are more likely to experience a depressive episode, while men are more likely to suffer from alcohol abuse and dependence. In fact, a subset of males who abuse alcohol may do so because of having undetected major depression. Effective treatment of their alcoholism may require concomitant treatment of their depressive illness.

Fortunately, advances have been made in the understanding of what constitutes appropriate and effective treatment, such as:

  • The development of eight pharmacologically unique classes of antidepressants with varying spectra of antidepressant activity (Chapters 6 through 8)
  • Better definition of what constitutes a therapeutic trial of an antidepressant in terms of dose and duration (Chapter 9)
  • An enhanced knowledge of clinically meaningful pharmacokinetics and pharmacodynamics to increase the safety and efficacy of these antidepressants (Chapters 6 and 10).

As a result of these developments, the prognosis of clinical depression is among the best of any major medical illness. Approximately 50% of patients with major depression fully remit when treated with any antidepressant. Of the remaining 50%, the majority will respond to monodrug treatment with an antidepressant from a mechanistically different class (Chapters 6 through 8).

Tragically, many patients are not treated.241 In one study, only 3.5% of over 6,000 cases of newly diagnosed depressed patients had received appropriate antidepressant treatment (eg, dose, duration). Hence, many "treatment refractory" cases are actually cases of inadequate treatment.


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