Mood Disorders—Depression

Tonya Fancher MD, MPH

Robert M. McCarron DO

Oladio Kukoyi MD

James A. Bourgeois OD, MD

A 42-year-old woman presents to your office complaining of insomnia. She reports four weeks of insomnia, decreased appetite, weight loss, fatigue, and depressed mood. She continues to work but socializes less than usual. Twenty years ago she had a similar episode and sought a brief course of counseling. Her symptoms improved over several months. She has never been on medications for depression and has no family history of mental illness. She denies suicidal ideation or access to firearms. Her examination is notable for tearfulness and a blunted affect, but is otherwise normal.

CLINICAL HIGHLIGHTS

Major depressive disorder is characterized by a depressed mood most of the day nearly every day or a significant loss of interest or pleasure in almost all activities (anhedonia) for a period of 2 weeks or more. Various other specific depressive syndromes are characterized by both duration and number of mood symptoms.
Roughly 10% of patients in primary care settings meet the criteria for major depressive disorder.
Depression is common among postpartum women and patients with a personal or family history of depression, the experience of a recent trauma or loss, ongoing substance abuse, and comorbid systemic medical illnesses such as cancer, diabetes mellitus, neurologic disease, and cardiovascular disease.
The U.S. Preventive Services Task Force recommends that primary care practices should screen all adults for depression if the practice has systems in place to formally diagnose, treat, and follow patients with depression. The Physician Health Questionnaire, or PHQ-9, is a self-administered screening tool for depression that can be easily used in the primary care setting.
Most patients with depression respond well to psychotherapy, antidepressants, or a combination of both.
Sixty percent of those with major depressive disorder will have a second episode. Individuals who have had two to three major depressive episodes have an 80% to 90% chance of having yet another episode. Patients with recurrent depression should be educated about the early signs of depression and be on lifelong antidepressant therapy.
Suicide can occur at any phase of treatment for depression. More than half of all patients who die by suicide have visited their primary care provider within 1 month of their death.
More than 70% of men and 50% of women who die by suicide used a firearm. Physicians should ask depressed or anxious patients about suicidal ideation and access to firearms at each visit.

Clinical Significance

Up to 10% of patients seen in primary care settings meet the criteria for major depressive disorder (1). The prevalence of major depressive disorder is closer to 30% to 40% among patients with such chronic medical illnesses as coronary artery disease (CAD), cerebrovascular disease, diabetesmellitus, obesity, and human immunodeficiency virus (HIV). Depression is the leading cause of disability and premature death in people aged 18 to 44 years and is associated with worsening medical morbidity and mortality (2, 3). For example, depression in patients with CAD has been consistently demonstrated to be an independent risk factor for increased cardiac mortality (4).

Up to one quarter of adults will have a major depressive episode during their lifetime (5). For the primary care clinician, untreated depression may help explain poor adherence to appointment keeping and prescribed treatments. Women are affected by depression twice as often as men. The lifetime risk of depression increases by 1.5 to 3.0 times in patients with an affected first-degree relative. Onset of depression is most common among patients aged 12 to 24 years and those over 65. The suicide rate is similarly high in both groups.

Diagnosis

Early diagnosis and treatment of depression usually improve a patient’s quality of life and health outcomes, and may prevent suicide. Most patients with depression seek care from their primary care provider before presenting to a mental health provider. Increasingly, primary care physicians are managing depression alone or in consultation with
a mental health provider. Major depression is defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), as the presence of five or more depressive symptoms over a 2-week period (depressed mood or lack of interest in pleasurable activities must be present). The collective symptoms cause significant dysfunction and cannot be due to other illnesses such as anxiety, hypothyroidism, or alcohol- or substance-related disorders (1) (Table 2.1).

Patients who do not meet the criteria for major depression may have a subsyndromal depression such as minor depression or dysthymic disorder. These types of depression are distinguished based on the length and number of symptoms in addition to sad mood and anhedonia, the degree of functional impairment, and the severity of symptoms. Minor depression is characterized by two to four depressive symptoms, including depressed mood or anhedonia, of greater than 2 weeks in duration. Dysthymic disorder is usually described as a chronic feeling of “being down in the dumps” and is characterized by at least 2 years of three or more depressive symptoms, including depressed mood, for more days than not. Also, in order to meet DSM-IV-TR criteria, depressive symptoms will not have been absent for more than 2 months during the 2 or more year-long period of dysthymic disorder.

Major depression can be stratified into three levels of severity: mild, moderate, or severe. A diagnosis of mild depression is indicated when no or few additional symptoms beyond the number required for diagnosis of major depression are present in the setting of minor functional impairment. Moderate depression is diagnosed when more than the required number of symptoms for the diagnosis of major depression are
present and there is moderate impairment in functioning. Severe depression is suggested by the presence of many more symptoms than required for the diagnosis of major depression and related disabling functional impairment. Psychotic features such as hallucinations or delusions may be present in severe depression. Suicidal ideation may accompany mild, moderate, or severe depression.

Table 2.1 DSM-IV-TR Definition of Major Depression

Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning.

At least one of the symptoms is either depressed mood or loss of interest or pleasure.
Depressed mood most of the day, nearly every day, as self-reported or observed by others
Diminished interest or pleasure in all or almost all activities most of the day, nearly every day
Significant weight loss when not dieting, or weight gain; or decrease or increase in appetite nearly every day
Insomnia or hypersomnia nearly every day
Psychomotor agitation or retardation as described by people who know the patient
Fatigue or loss of energy nearly every day
Feelings of worthlessness or excessive or inappropriate guilt nearly every day
Diminished ability to think or concentrate nearly every day
Recurrent thoughts of death; recurrent suicidal ideation without a specific plan

From Diagnosis and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

IDENTIFYING HIGH-RISK POPULATIONS

There are currently no diagnostic tests or laboratory makers that reliably estimate risk for the development of depression. Moreover, there is much controversy over the actual cause of depression. Although there is strong evidence to support a familial link among first-degree relatives who have depression, there is currently no definitive genetic association with the development of major depressive disorder.

The U.S. Preventive Services Task Force recommends that primary care practices should screen all adults for depression if the practice has systems in place to formally diagnose, treat, and follow patients with depression (6). The following section provides an overview of risk factors for the development of depression. Patients with risk factors should be screened on the initial primary care visit and at least every 1 to 2 years thereafter.

Postpartum Women

Postpartum women often have abrupt hormonal shifts and related short-lived depression commonly referred to as “the blues.” Most such subsyndromal, postpartum depressive episodes will subside gradually with supportive care over 1 to 2 weeks after the delivery. In other words, the majority of new mothers will not have the full neurovegetative signs or mood disturbance duration characteristic of a major depressive episode. It is difficult to predict which women will progress to full-spectrum postpartum depression, but women with a previous mood disorder, poor social support, and delivery following an unplanned or unwanted pregnancy are at particularly high risk for postpartum depression. Continued clinical vigilance for up to 1 year after the delivery is indicated for all postpartum women.

Up to 1 in 10 women in the postpartum period will develop major depression (7). Clinicians can screen for postpartum depression using the Edinburgh Postnatal Depression Scale approximately 4 to 6 weeks after delivery. Postpartum depressive episodes are more likely to be complicated by psychotic symptoms, which may lead to poor infant care, infanticide, or suicide.

Personal or Family History of Depression

A personal history of major depression or bipolar disorder is the most significant risk factor for recurrent depression. Major depressive disorder is up to three times more likely among those with first-degree relatives who have either depression or bipolar disorder (1). A family history of depression is also associated with longer depressive episodes, greater risk of recurrence, and persistent thoughts of death and suicide (8).

Advanced Age

Elderly patients with depression can present with apathy, diminished self-care, or severe cognitive deficits. Depression is also common among caregivers of the elderly (9). Elderly depressed patients often have increased primary care utilization for nonspecific physical complaints and may present with significant weight loss and failure to thrive. Depression is also common in patients with dementia.

Neurologic Disorders

The risk of depression is very high in the first year following a stroke. Poststroke depression correlates with failure to regain motor function, more medical complications, and cognitive impairment. Parkinson disease is also frequently complicated by depression. The depression in Parkinson disease may have a greater impact on quality of life than impairment from the associated movement disorder. Patients with chronic neurologic disorders like stroke and Parkinson disease should be watched closely for the emergence of depression or anhedonia.

Comorbid Systemic Physical Illnesses

Patients with diabetes mellitus, cancer, rheumatologic disease, thyroid disease, HIV, myocardial infarction, and obesity have significantly higher rates of depression. At least one quarter of those with cardiac disease or diabetes will develop major depressive disorder. Patients may present atypically with nonadherence, multiple unexplained physical symptoms, or chronic pain syndromes (10, 11, 12, 13, 14, 15, 16 and 17). Early recognition and treatment of depression can improve morbidity, mortality, and quality of life.

PATIENT ASSESSMENT

The U.S. Preventive Services Task Force encourages routine depression screening for adults in primary care practices that have the resources to treat and follow the identified patients (6, 18). Clinicians with limited resources may consider screening mainly at-risk groups. Clinicians should consider repeated screenings of patients with a history of depression or other psychiatric symptoms, comorbid medical illness, multiple unexplained somatic complaints, high rates of clinical utilization, substance abuse, chronic pain, or nonadherence. Patients should also be asked about the use of recent or current medications that have been associated with depressive symptoms or suicidal ideation (e.g., corticosteroids, interferon, montelukast sodium, varenicline, isotretinoin).

There are no definitive findings of depression on physical examination, although many patients demonstrate a tearful, blunted, or restricted affect. Depressed patients may also have psychomotor retardation or a quiet and slow speech pattern. The physical examination may be useful in helping to rule out common conditions that are often confused with depression (e.g., hypothyroidism, dementia) and in looking for commonly co-occurring illnesses (e.g., obesity, cancer, CAD). When clinical suspicion is high, laboratory testing might include tests for anemia, hypothyroidism, vitamin B12 deficiency, and Cushing disease.

Screening Tools and Rating Scales for Depression

The most important first step in the diagnosis of depression is to ask about depressed mood and anhedonia over the past 2 or more weeks. One of the easiest depression screening tools is the two-question Patient Health Questionnaire-2 tool (PHQ-2) (19, 20):

“Over the past 2 weeks have you felt down, depressed, or hopeless?”

“Over the past 2 weeks have you felt little interest or pleasure in doing things?”

A positive response to either question warrants a thorough review of the DSM-IV-TR criteria (or equivalent rating tool) for major depression (Figure 2.1).

An alternative screening tool is the Patient Health Questionnaire-9 (PHQ-9) (Figure 2.2). The PHQ-9 can be used to diagnose depression and to follow the disease over time. It has been validated in primary care settings, is self-administered, and is available in English and Spanish versions (21, 22 and 23). It is a nine-item self-administered questionnaire that classifies current symptoms on a scale of 0 (no symptoms) to 3 (daily symptoms) (21). Items 1 through 9 are summed to yield a score ranging from 0 to 27. A score of 0 to 4 is considered nondepressed, 5 to 9 mild depression, 10 to 14 moderate depression, 15 to 19 moderately severe depression, and 20 to 27 severe depression. Repeating the PHQ-9 during treatment allows the clinician to objectively monitor response to therapy: a 50% reduction in symptom score suggests an adequate response; a 25% to 50% reduction suggests a partial response, and a reduction by less than 25% suggests a minimal to no response. Patients who fail to respond to initial treatment may warrant an urgent psychiatric referral.

Two items from the PHQ-9 deserve particular attention. Item 9 assesses suicidal ideation. Any positive response should be followed up with direct questioning about suicidal ideation, intent, and planning. Item 10 assesses functional impairment. Like symptom severity, severe functional impairment may suggest the need for psychiatric consultation and consideration for hospitalization (24, 25).

Additional rating instruments for the clinical assessment of depression include the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and the Zung Self-Rating Depression Scale. The HAM-D is a clinician-administered instrument. Both 17-item and 31-item versions are available, although the 17-item version is more widely used. It relies both on patient-reported symptoms and clinician observation of in-interview behavior (26). Although various cut-off scores have been used to define both syndromal depression and remission from a depressive episode, we use a cut-off of greater than 16 to define a major depression episode and a score of less than 7 to define a remission (27, 28). Because it is clinician administered, the HAM-D has the advantage of including clinician behavioral observations into an overall rating score; however, the length of time required to complete the HAM-D may make it impractical for some clinicians. Like the PHQ-9, the BDI and the Zung are patient self-rating instruments (29, 30). The Zung is a 20-item scale with 10 positively scored items and 10 negatively scored items. Scores of 50 to 59 correlate with mild depression, 60 to 69
with moderate to severe depression, and greater than 70 with severe depression. The BDI contains 21 items; scores of 0 to 9 represent minimal symptoms, 10 to 16 mild depression symptoms, 17 to 29 moderate symptoms, and 30 to 63 severe symptoms. Generally, the PHQ-9 is the easiest for the primary care provider to use.

Figure 2.1 Diagnosing depression in the primary care setting.

Figure 2.2 Patient Health Questionnaire (PHQ-9) nine-symptom depression checklist. (PHQ is adapted from PRIME MD TODAY. PHQ Copyright © 1999 Pfizer Inc. All rights reserved. Reproduced with permission. PRIME MD TODAY is a trademark of Pfizer Inc.)

Suicide Risk Assessment

Clinicians must remain vigilant to the risk of suicide as up to 15% of those with major depressive disorder die by suicide (1). Suicide is consistently a leading cause of death in the United States, accounting for more than 30,000 deaths per year (31). Many patients who die by suicide meet criteria for a depressive disorder and nearly half have seen a primary care physician within a month of their death (32, 33). Clinicians should routinely ask (and document asking) depressed patients if they have had or currently have any thoughts of suicide, of ending their life, or that they would be better off dead. Positive responses should be followed by assessment of the content of suicidal thoughts (including specific plans or actual intent of suicide) and reduction of access to lethal means (especially firearms and medications that may be harmful if taken in large quantities). Clinicians should consult a psychiatrist if there is any uncertainty regarding suicidal risk or need for hospitalization.

Differential Diagnosis

In addition to the systemic illnesses associated with and presenting as depression, many other psychiatric illnesses are associated with depressed mood and other symptoms of depression. “All that is depressive may not be depression” is a useful reminder of this phenomenon. We recommend using the AMPS approach to the psychiatric review of systems when assessing anyone who presents with sadness or anhedonia (see Chapter 1).

Depressive symptoms may be present with psychiatric disorders other than the depressive disorders of major depression, dysthymic disorder, or minor depression. In bipolar disorder, a patient may present with depressive symptoms as part of a depressive or mixed mood episode. Patients with psychotic disorders (e.g., schizophrenia or schizoaffective disorder) may, at some points during their illness, present with prominent symptoms of depression. Anxiety disorders (particularly panic disorder and posttraumatic stress disorder) may coexist with depression or feature prominent depressive symptoms.Dementia and delirium have well-known associations with depressive symptoms; dementia is often associated with comorbid depression, while hypoactive delirium may physically resemble depression. During or following periods of substance abuse, a person may have a substance-induced mood disorder. If depressive symptoms are mild or transient, a personmay have an adjustment disorder or bereavement (Table 2.2).

Biopsychosocial Treatment

GENERAL PRINCIPLES

The goals of depression treatment include reducing symptoms of depression, improving daily functioning and quality of life, eliminating suicidal thoughts, minimizing treatment adverse effects, and preventing depression relapse. Medication and psychological therapies are most frequently and successfully used to treat depression. Patients who experience full clinical remission have a better long-term prognosis than patients with only a partial response to therapy (34, 35).

Table 2.2 Differential Diagnosis for Major Depressive Disorder

Alcohol abuse/dependence	Can co-occur with depression, mimic depressive symptoms, or actually cause depression. At lease 4 weeks of abstinence is necessary when ruling out depression that is secondary to alcohol use.
Anxiety disorders	Anxiety disorders frequently co-occur with depression. Both generalized anxiety disorder and more episodic, circumstance-specific anxiety disorders (i.e., panic disorder, social phobia, specific phobia, obsessive compulsive disorder, posttraumatic stress disorder, acute stress disorder) should be addressed when present.
Bipolar disorder	Depression is accompanied by a history of one or more manic or mixed episodes. Many patients with bipolar disorder are depressed at the time of initial clinical presentation.
Cobalamin deficiency	Vitamin B₁₂ deficiency is associated with macrocytic anemia, paresthesia, numbness, and impaired memory.
Cushing disease	This condition is associated with obesity, dermatologic manifestations, signs of adrenal androgen excess, and proximal muscle wasting.
Dementia	Dementia is characterized by memory changes, mood symptoms, personality changes, psychosis, problematic social behaviors, and changes in day-to-day functioning. Comorbid depression is very common in dementia.
Eating disorders	These disorders are more common in women and sometimes characterized by disturbance in the perception of body weight, size, or shape, and refusal to maintain a healthy body weight in the case of the anorexia nervosa syndrome and impulsive binge eating with compensatory purging behaviors in the bulimia nervosa syndrome. Depression is commonly comorbid in eating disorder patients.
Bereavement	The symptoms of major depression may be transiently present in normal grief. The duration and expression of normal grief vary among racial/ethnic groups. Temporarily hearing the voice of or seeing the deceased person is considered within normal limits of bereavement. Patients with unremitting and significantly impaired function attributable to these mood symptoms should be fully assessed for major depressive disorder.
Hypothyroidism	Associated symptoms include weight gain, constipation, decreased concentration, fatigue, disturbance with sleep, and depressed mood.
Medication adverse effects	Patient should be asked about use of glucocorticoids, interferon, levodopa, and oral contraceptives.
Premenstrual dysphoric disorder (PMDD)	PMDD is characterized by depressed mood, anxiety, and irritability during the week before menses and resolving with menses. PMDD also has prominent pain symptoms.
Psychotic disorders	Patients with major depression may have psychotic symptoms during acute depressive episodes. Mood-congruent hallucinations and delusions are commonly found in patients who have depression with psychotic features. A temporal correlation between increased depressed mood and increased psychotic symptoms is often present with a diagnosis of depression with psychotic features.
Secondary depression	This is depression due to the physiologic consequences of a specific metabolic disturbance, recent drug or substance use, or substance withdrawal. It often remits with treatment of the disorder, removal of the drug or substance, or recovery from withdrawal, but, if persistent, may need specific antidepressant therapy. At least 4 weeks of abstinence is necessary when ruling out depression due to stimulant use.
Adjustment disorder with depressed mood	This is a subsyndromal depression with a clearly identified precipitating event. It usually resolves with resolution of the acute stressor. Although it is not the norm, in some circumstances, a diagnosis of adjustment disorder may justify the short-term use of sedative-hypnotic and antidepressant medications.