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The diagnostic criteria for major depression are anhedonia, depressed mood, feelings of worthlessness or inappropriate guilt, inability to concentrate, fatigue, insomnia or hypersomnia, psychomotor agitation or retardation, significant weight loss or gain, and recurrent thoughts of death or suicide. Five or more of these symptoms must be present for at least 2 weeks, and one of them must be anhedonia or depressed mood. Conditions that can present with depression include dysthymia, bipolar disorder, cyclothymia, and adjustment disorder. Depression may also result from substance abuse or from the physiological conditions associated with a medical disorder, such as spinal or head injury, AIDS, or cancer.


Depression is a common, recurrent, often debilitating, and potentially lethal disorder. About 1 in 10 outpatients have clinical, or major, depression.1,2 The lifetime prevalence rate for a major depressive episode is 3.2% to 4.4% for men and 4.9% to 8.7% for women.3,4 Depression is more common in persons with medical illnesses; it affects 11% to 36% of general medical inpatients.5

In this 2-part series, I review the diagnosis and treatment of depression in the primary care setting. Here I summarize the diagnostic criteria, describe conditions that can present with depression, and discuss the assessment of suicide risk. In a coming issue, I address treatment.


The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)6 lists the following criteria for major depression:

•Loss of pleasure in usual activities (anhedonia).
•Depressed mood.
•Feelings of worthlessness or inappropriate guilt.
•Inability to concentrate.
•Fatigue or loss of energy.
•Insomnia or hypersomnia.
•Psychomotor agitation or retardation.
•Significant weight loss or gain.
•Recurrent thoughts of death or suicide.

Five or more of these symptoms must be present for at least 2 weeks, and one of them must be anhedonia or depressed mood.


Dysthymic disorder (dysthymia). This is a chronic, low-grade depressive state that persists for at least 2 years (Table 1). Although the depressive symptoms are not completely disabling, they prevent the patient from achieving his or her full potential. Dysthymic disorder can coexist with major depression; this is sometimes referred to as “double depression.”

Bipolar disorder. Between 0.4% and 1.2% of American adults have bipolar disorder, and the lifetime risk of developing this disorder is roughly 1%.2 Patients with bipolar disorder-which was formerly known as manic depressive psychosis-experience mood swings alternating between severe depressive mood and extreme, inappropriate elevated mood, or mania. The depressive episodes resemble major depression, while the manic episodes are characterized by increased energy, decreased need for sleep, grandiosity, racing thoughts, hyper-talkativeness (pressured speech), hyperactivity, and increased sexual desires. Irritability, aggression, and impulsive activities may also accompany the manic episodes.

When major depressive episodes alternate with manic episodes, the condition is described as bipolar type I disorder. Bipolar type II disorder is characterized by episodes of depression that alternate with episodes of hypomania. The symptoms of hypomania (eg, euphoria or irritability) are milder and of shorter duration than those of mania; they do not dramatically affect work or social life.

Cyclothymic disorder (cyclothymia). This chronic mood disorder is characterized by short periods of mild depression and of hypomania; these episodes last from a few days to a few weeks and are separated by short periods of normal mood. Persons with cyclothymic disorder are never free of symptoms of either depression or hypomania for more than 2 months.

Adjustment disorder with a depressed mood. This is a mild, reactive depression that lasts only a few months; it occurs in response to a specific stressful situation. Symptoms may include sadness, feelings of emptiness, loss of interest and pleasure, irritability, anger, changes in appetite, sleep problems, restlessness, slow movement and thinking, fatigue, worthlessness, guilt, poor concentration, and thoughts about death and suicide. After the stressful situation resolves, the symptoms usually decrease and disappear within a few months.

Depression caused by a general medical condition. This mood disorder results from physiological conditions associated with a medical disorder. It usually subsides following the appropriate diagnosis and treatment of the disorder.

Clinical depression is not a normal part of coping with a medical condition. In fact, the presence of clinical depression can complicate recovery. Having a depressive mood disorder along with a serious medical condition can increase the risk of suicide. The greatest risk of suicide is associated with chronic, painful, or terminal illnesses, such as spinal cord injury, head injury, AIDS, malignancy, severe burns, and chronic pain.

To determine whether depression results solely from the patient’s medical condition or from a combination of the condition and an underlying mood disorder, it may be helpful to focus on the following:

•Ask about symptoms that are more likely psychological than physiological, such as guilt, worthlessness, helplessness, hopelessness, loss of pleasure, and suicidal ideation.

•Inquire about a personal or family history of depression.

•Search for metabolic or physiological causes of the depression.

Substance-induced depression. Depression may be caused or precipitated by the use or abuse of illicit drugs, alcohol, medications, and herbal supplements or by exposure to toxins. Determine whether the mood disorder results from such use or exposure or whether it occurs at the same time by coincidence. To make a diagnosis of a substance-induced mood disorder, the disturbance can occur only while a person is intoxicated or undergoing withdrawal, or within 4 weeks of intoxication or withdrawal.

Seasonal affective disorder (SAD). This mood disorder is associated with depressive episodes during the winter; symptoms subside during the spring and summer. SAD is related to the seasonal variations in sunlight exposure. The most difficult months for affected persons are January and February in the northern hemisphere and July and August in the southern hemisphere. This condition seems to be more prevalent in younger persons and women.

Depression not otherwise specified. In this condition, depressive symptoms are present but they do not meet the criteria for any specific mood disorder.


Once a mood disorder is diagnosed, more detailed information can be provided in the form of “specifiers.” The use of specifiers helps in selecting the most effective treatment and in predicting the course and prognosis of the illness. Specifiers may be considered as subcategories of the larger categories of depressive disorders. The following is an example of a diagnosis with specifiers: major depressive disorder, single episode, moderate, with atypical features.

Specifiers that may be used to describe the degree of the episodes are:

Mild: Few or no symptoms beyond what is needed to make a diagnosis are present. The patient can function normally, although with extra effort.

Moderate: The severity of symptoms ranges between mild and severe. For a manic episode, the patient’s activity is increased or judgment is impaired.

Severe without psychotic features: Most symptoms are present, and the patient has little or no ability to function. During a manic or mixed episode, the patient needs to be supervised to prevent harm to self or others.

Severe with psychotic features: The patient experiences hallucinations or delusions. Psychoses may develop in about 15% of those with major depressive disorder.2 The delusions and hallucinations often interfere with patients' ability to make sound judgments about the consequences of their actions, and this may put them at risk for self-harm. Patients with psychotic symptoms require immediate medical attention and possibly hospitalization.

Other specifiers that are used to further characterize the episodes are:

Single episode/recurrent: A first episode is considered “single”; subsequent episodes are “recurrent.”

Partial/full remission: Full remission is defined as the absence of symptoms for at least 2 months. For partial remission, the full criteria for a major depressive episode are no longer met, or the patient has had no substantial symptoms for less than 2 months.

Chronic: For at least 2 years, the patient's symptoms have met the criteria for major depression.

Catatonic features: Unusual behaviors or movements, such as immobility, excessive activity that is purposeless, rigid or peculiar posturing, and mimicking others’ words or behaviors.

Melancholic features: A loss of pleasure in most activities or an inability to feel better, even for a short time, when something pleasurable happens. Also, at least 3 of following are present: the depressed mood is distinct (ie, different from feelings of bereavement), mood is worse in the morning, the patient wakes too early in the morning, there is distinct agitation or movements are slowed down, substantial weight loss occurs, or the patient has extreme feelings of guilt.

Melancholic features are associated with the presence of a specific precursor to the illness and a better response to antidepressants. Men and women are equally likely to have these features, although they are more common in older adults. They may also be more likely to occur in more severe depressive episodes, particularly those with psychotic features.

Atypical features: During the last 2 weeks of an episode of major depression or a depressive episode of bipolar disorder, or during the last 2 years of dysthymic disorder, the patient is able to experience brightened mood when pleasurable events occur. Also, at least 2 of the following must be present: substantial increase in weight or appetite, sleeping too much at night or daytime napping (ie, at least 10 hours total or 2 hours beyond normal), body feels heavy or weighted down, or persistent sensitivity to rejection by others that is related to personal or social difficulties.

The sensitivity to rejection tends to be a long-standing problem. Depression may increase the sensitivity, although it is often present when the person is not depressed.

Atypical features occur 2 to 3 times more often in women. They are also associated with depression beginning at an earlier age (eg, during adolescence) and possibly more chronic depressive episodes. Personality and anxiety disorders may also be more common.

Postpartum onset: The depressive episode begins within 4 weeks of giving birth.

With/without full inter-episode recovery: Describes a long-term course of recurrent major depression or bipolar disorder. The specifiers indicate whether the patient recovered from the symptoms between the 2 latest episodes.

Seasonal pattern: Describes a pattern of depressive episodes in recurrent major depression or bipolar disorder. The symptoms tend to begin (usually in the fall or winter) and end (usually in the spring) at particular times of the year.

Rapid cycling: Describes a recurrent pattern of depressive and manic episodes in bipolar disorder. The patient has had at least 4 mood disorder episodes during the past 12 months. There is either a general absence of symptoms between episodes or a clear switch from one mood disorder to its opposite, such as from depression to mania. Rapid cycling may affect 5% to 15% of those with bipolar disorder, and women account for 70% to 90% of those with this pattern.2 Certain medical conditions may be related to rapid cycling, such as neurological disorders, hypothyroidism, head injury, and mental retardation, as well as treatment with antidepressants. Patients who experience rapid cycling may have a less favorable prognosis.


Depressed patients frequently contemplate suicide. Table 2 lists some of the warning signs.7

During the initial evaluation, ask specific questions, such as, “Do you ever think of hurting yourself or taking your own life?” If the answer is yes, this should be followed by “Do you currently have a plan?” and if the answer is yes, “What is your plan?” Do not avoid these questions for fear of suggesting the idea of suicide.

If patients are unsure of their ability to resist suicidal urges or if you are concerned that certain patients may not seek help before harming themselves, emergency psychiatric evaluation becomes critical. Even in the absence of immediate risk, emphasize to patients the importance of reporting suicidal thoughts, especially if they are becoming more intense or more frequent.7Table 3 summarizes the risk factors for suicide in patients with major depression.

The author thanks the VA Medical Center director, Mr Alan Perry, and the chief of staff, Dr William Cahill, for their administrative support; Drs Robert Hierholzer, Nestor Manzano, Scott Ahles, and Craig C. Campbell, for their clinical guidance; Dr Avak A. Howsepian for his constructive criticism; Dr Matthew Battista and Leonard Williams, PA-C, for their encouragement; and Ms Emma Nichols for her computer assistance.




Broadhead WE, Blazer DG, George LK, Tse CK. Depression, disability days, and days lost from work in a prospective epidemiologic survey.




Robins LN, Regier DA, eds.

Psychiatric Disorders in America, the Epidemiologic Catchment Area Study.

New York: The Free Press; 1990.


Ferketich AK, Schwartzbaum JA, Frid DJ, Moeschberger ML. Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey.

Arch Intern Med.



Covinsky KE, Fortinsky RH, Palmer RM, et al. Relation between symptoms of depression and health status outcomes in acutely ill hospitalized older persons.

Ann Intern Med.



Wells KB, Stewart A, Hays RD, et al. The functioning and well-being of depressed patients: results from the Medical Outcomes Study.




American Psychiatric Association.

Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR).

4th ed. Washington, DC: American Psychiatric Association; 2000.


Whooley MA, Simon GE. Managing depression in medical outpatients.

N Engl J Med.



•Khouzam HR, Tan DT, Gill TS.

Handbook of Emergency Psychiatry.

Philadelphia: Mosby; 2007.

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