1. Maintain a high index of suspicion and evaluate risk factors

Surveys consistently show that 6 to 8 percent of all outpatients in primary care settings have major depressive disorder; women are at particular risk for depression. Although sadness is frequently a presenting sign of depression, not all patients complain of sadness, and many sad patients do not have major depression. Common complaints of patients in primary care settings with major depressive disorder include:

• Pain--including headaches, abdominal pain, and other body aches.

• Low energy--excessive tiredness, lack of energy or a reduced capacity for pleasure or enjoyment.

• A mood of apathy, irritability, or even anxiety rather than, or in addition to, any overt sadness may be present.

• Sexual complaints--problems with sexual functioning or desire.

The clinician should be doubly alert to the likelihood of depression in individuals under age 40.

Additional clinical clues that raise the likelihood of a major depressive disorder include:

• Prior episodes of depression.

• A family history of major depressive or bipolar disorder.

• A personal or family history of suicide attempt(s).

• Concurrent general medical illnesses.

• Concurrent substance abuse.

• Symptoms of fatigue, malaise, irritability, or sadness.

• Recent stressful life events and lack of social supports. (Stress should not be used to "explain away" depression; stress may precipitate a depression in some cases.)

2. Detect depressive symptoms with a clinical interview

Major depressive disorder is a syndrome consisting of a constellation of signs and symptoms that are not normal reactions to life's stress. A sad or depressed mood is only one of the several possible signs and symptoms of major depressive disorder. The clinician may find it useful to provide the patient with a written list of depressive symptoms (pages 3 and 4) and ask the patient to indicate any symptoms experienced. This patient self-report can increase the likelihood of detecting major depression.

Diagnosis

Diagnostic criteria for major depressive disorder

For major depressive disorder, at least five of the following symptoms are present during the same time period, and at least one of the first two symptoms must be present. In addition, symptoms must be present most of the day, nearly daily, for at least 2 weeks.

• Depressed mood most of the day, nearly every day.

• Markedly diminished interest or pleasure in almost all activities most of the day, nearly every day (as indicated either by subjective account or observation by others of apathy most of the time).

• Significant weight loss/gain.

• Insomnia/hypersomnia.

• Psychomotor agitation/retardation.

• Fatigue (loss of energy).

• Feelings of worthlessness (guilt).

• Impaired concentration (indecisiveness).

• Recurrent thoughts of death or suicide.

Source: American Psychiatric Association, 1987.

All depressed patients should be assessed for the risk of suicide by direct questioning about suicidal thinking, impulses, and personal history of suicide attempts. Patients are reassured by questions about suicidal thoughts and by education that suicidal thinking is a common symptom of the depression itself and not a sign that the patient is "crazy." Table 1 lists the risk factors associated with completed suicide.

Table

Table 1. Suidice risk Factors.

If suicide is a distinct risk (specific plans, or significant risk factors exist), consult a mental health specialist immediately. The patient may need specialized care or hospitalization.

Bipolar illness

A small percentage of patients with major depressive disorder have bipolar illness. These patients experience mood cycles with discrete episodes of depression and mania. In between episodes, they may feel perfectly normal.

Diagnostic criteria for mania

For mania, at least four of the following symptoms, including the first one listed, must be present for a period of at least 1 week.

• A distinct period of abnormally and persistently elevated, expansive, or irritable mood

• Less need for sleep.

• Talkative or feeling pressure to keep talking.

• Distractibility.

• Flight of ideas.

• Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.

• Inflated self-esteem or grandiosity.

• Excessive involvement in pleasurable activities which have a high potential for painful consequences (buying sprees, sexual indiscretions, or foolish business investments).

Source: American Psychiatric Association, 1987.

3. Diagnose the mood disorder using clinical history and interview

Many patients are aware of only some symptoms and may minimize their disability. Interviewing someone who knows the individual well (a spouse, close friend, or relative) can be extremely valuable in obtaining an accurate picture of the patient's symptoms, degree of disability, and course of illness.

4. Evaluate patients with a complete medical history and physical examination

The patient's initial complaints should be evaluated thoroughly with a medical review of systems and a physical examination. If no cause or associated factors can be found for the initial presenting medical complaint, diagnose the patient for a primary mood syndrome.

5. Identify and treat potential known causes (if present) of mood disorder

Approximately 10-15 percent or more of major depressive conditions are caused by general medical illnesses or other conditions (See Figure 2). Generally, the principle is to treat the associated condition first. If the depression persists after treatment of the associated condition, major depressive disorder should be diagnosed and treated.

Figure

Figure 2. Conditions associated with mood symptoms of major depressive episodes.

Figure 1. Differential diagnosis of primary mood disorders

Potential associated conditions include

Substance abuse

Too much alcohol, use of illicit drugs, or abuse of prescription medicines can cause or complicate a major depressive episode. In most cases, once the substance has been discontinued, the depression lifts (Figure 3).

Figure

Figure 3. Relationship between major depressive and other current psychiatric disorders.

Concurrent medication

Depression may be an idiosyncratic side effect of many medications. However, the clinician should be aware that this effect is uncommon and usually occurs within days to weeks of starting the medication. Current evidence clearly implicates only reserpine, glucocorticoids, and anabolic steroids with the de novo development of depression as a potential side effect of the drug. Changing to a different medication often relieves the depression (Figure 4).

Figure

Figure 4. Relationship between major depressive and other current general medical disorders.

General medical disorders

Depression can occur in the presence of another general medical condition (Figure 4) (most commonly, autoimmune, neurologic, metabolic, infectious, oncologic, and endocrine disorders, among others). There are several possibilities in such cases:

The general medical disorder biologically causes or triggers a depression; for example, hypothyroidism can be accompanied by depressive symptoms. In this case, treat the general medical disorder first.

The general medical disorder psychologically results in depression; for example, a patient with cancer may become clinically depressed as a reaction to the prognosis, pain, or incapacity, although most patients with cancer do not suffer a major depressive episode. In this case, treat the depression as an independent disorder.

The general medical disorder and the mood disorder are not causally related. In this case, treat the depression.

Other causal nonmood psychiatric disorders

These generally include eating disorders, obsessive-compulsive disorder, and some cases of panic disorder (Figure 3).

When generalized anxiety disorder co-exists with major depression, treatment should be directed toward the major depression first.

If panic disorder is present only during major depressive episodes, the major depression is treated first.

If panic disorder and major depression are both present and the panic disorder has been present without episodes of major depression in the past, the clinician must judge which is the most significant condition (e.g., by family history, the level of current disability attributable to each, and the prior course of illness) and treat that condition Figure 3. Relationship between major depressive and other current psychiatric disorders.

If a "personality disorder" is suspected, the major depressive disorder is treated first, whenever feasible.

Grief reaction

It is important to differentiate a normal grief reaction from depression. A normal grief reaction persists for 2 to 6 months and improves steadily without specific treatment. Most grief reactions do not meet criteria for a major depressive episode. Grief reactions are usually seen by patients as normal and appropriate. While unpleasant, they rarely cause significant and prolonged impairment in work or other functions. Some individuals experience symptoms of depression along with the grief reaction. If the major depressive episode persists for more than 2 months after the loss, a major depressive disorder should be diagnosed and treated.

6. Reevaluate for mood disorders

If the depression persists after treatment of the associated psychiatric general medical, or substance abuse disorders, the depression should be diagnosed and treated.

7. Develop a treatment plan with the patient

If the mood disorder is still present, or if associated conditions do not exist, work with the patient to treat the primary mood disorder.

Treatment of depression consists of three phases (Figure 5):

• Acute treatment (6 to 12 weeks) aims at remission of symptoms. A partial response (not a complete remission) is associated with a poorer prognosis.

• Continuation treatment (4 to 9 months) aims at prevention of relapse. During this phase, medication should be continued at the full dosage. Continuation phase psychotherapy may be helpful for selected individuals.

• Maintenance treatment aims at prevention of recurrence in patients with prior episodes. Only maintenance medication prevents a new episode (recurrence). Maintenance psychotherapy may delay the next episode

Figure

Figure 5. Phases of treatment for major depression.

The objective of treatment is for the patient to reach a sustained asymptomatic state. Figure 6 presents a flow diagram for the treatment of depression. These principles apply no matter what treatment is selected. The essential features of this plan include:

• Patient education prior to treatment (page 10).

• Regular monitoring for side effects.

• Regular monitoring of the patient's depressive symptoms.

• Adjustment or changes in the treatment plan if response is not timely or complete.

Figure

Figure 6. Overview of treatment for depression.

8. Select the most appropriate acute phase treatment

The aim of acute phase treatment is symptom remission. Treatment of depression in the primary care setting includes:

• Medication.

• Psychotherapy.

• Combined treatment of medication and psychotherapy.

The choice of treatment modality is based primarily on the history of illness and the severity of the major depressive episode. The following general definitions may be helpful in determining an appropriate treatment:

• Severe depression is present when a person has nearly all of the symptoms of depression, and the depression almost always keep them from doing their regular day-to-day activities.

• Moderate depression is present when a person has many symptoms of depression that often keep them from doing things that they need to do.

• Mild depression is present when a person has some of the symptoms of depression, and it takes extra effort to do the things they need to do.

9. If medication is used, select the type and dose best suited to the patient

Primary care providers will find it useful to become familiar with one drug with minimal side effects from each of the major classes of antidepressants (Tables 2 and 3).

Table

Table 2. Side-effect profiles of antidepressant medications.

Table

Table 3. Pharmacology of antidepressant medications.

Medications should be individualized to the patient in order to optimize treatment benefit and lower risk. Factors to be considered include:

• Possibility of short- and long-term side effects.

• History of response or nonresponse.

• Consideration of possible drug interactions.

• Presence of other psychiatric and general medical conditions.

• Patient age. Elderly patients are at much higher risk for concomitant general medical disorders and should, therefore, receive a more thorough medical evaluation prior to treatment.

Patients at risk of experiencing adverse drug interactions or with other medical illnesses may need lower than recommended dosages. Geriatric patients often require lower dosages of medication, and dosage increments should be made slowly.

10. Evaluate treatment response

Whether medication, psychotherapy, or a combination are used, evaluate the patient's response to treatment.

Medication

Adequate response—

Many patients will respond to an adequate trial of the first drug tried.

Inadequate response --

Figure 7 summarizes the steps in managing partial or nonresponse to medication. If inadequate response is a problem, the following steps may be taken:

• Reevaluate the diagnosis.

• Evaluate for side effects.

• Inquire about medication adherence.

• Determine the need for increased dosing. For tricyclic agents, the primary cause of inadequate response is insufficient dosing. In selected cases, it may be useful to obtain blood drug levels to gauge dosing. (Minimal therapeutic blood levels have been fairly well documented for nortriptyline, desipramine, imipramine, and amitriptyline.)

• Change medication. Patients who do not respond to the initial medication trial are likely to respond to an alternate drug from a different class. If the patient still does not respond after a trial on a second drug, consultation with a mental health specialist should be strongly considered (Figure 7).

• Add or change to psychotherapy. Patients who cannot tolerate medication or who have only a partial response (with residual cognitive symptoms) in mild to moderate depression may benefit from time-limited psychotherapy (Figure 7).

Figure

Figure 7. Six-week evaluation: partial or nonresponders to medication.

11. Proceed to continuation phase treatment

Once the patient has responded to acute phase treatment with medication, continuation treatment is indicated. If acute phase psychotherapy alone was effective, continuation treatment with psychotherapy may be useful in selected cases. The aim of continuation treatment is to prevent the return of the most recent depressive episode (a relapse). The following principles apply:

• If the acute phase treatment included medication, continuation medication is always called for (Figure 8). The dosage is the same as that used in acute treatment. Medication visits can be extended to once every 2 to 3 months for most patients.

• If psychotherapy alone constituted acute treatment, the patient remitted, and psychosocial function was restored, psychotherapy may not be needed as a continuation treatment. While two studies are suggestive that continuation psychotherapy may reduce the relapse rate in those who respond to acute phase psychotherapy, the indications for continuation phase psychotherapy are unclear.

• If combined acute phase treatment was used, psychotherapy may be continued, or it may be discontinued if the patient is in remission and psychosocial function has been restored.

Figure

Figure 8. Six-week evaluation: responders to medication.

12. Evaluate the need for maintenance phase treatment

The goal of maintenance treatment is prevention of a recurrence of a major depressive episode. The efficacy of maintenance treatment in preventing a future episode of depression has been clearly demonstrated only with medication. The following principles apply:

• Maintenance medication treatment should be considered for selected cases after acute and continuation treatment. Patients who have had three previous episodes of depression should be maintained for one to several years on medication at the same dose that was effective in the acute phase of treatment.

• Maintenance medication treatment should be considered for patients with two episodes of major depressive disorder who also have:

• First-degree relative with bipolar disorder or recurrent major depression.

• History of recurrence within 1 year after previously effective medication was discontinued.

• Early onset (before age 20) of the first episode.

• Both episodes were severe, sudden, or life-threatening in the past 3-years.

• Maintenance psychotherapy can be useful in selected situations with recurrent major depressive disorder, such as women who want to become pregnant and bear a child in a drug-free condition or individuals who must be medication-free for a limited time period. Although maintenance psychotherapy has not been shown to prevent recurrence, one study suggests that it may help to delay the onset of the next episode.

13. Seek consultation

Consult with or referral to a mental health specialist (e.g., psychiatrist, psychologist, psychiatric nurse, social worker) can be useful in the following situations:

• The general guidelines cannot be followed or may not be suitable for the individual patient.

• The patient fails to respond fully to one or two medication trials.

• The patient is actively suicidal.

• The patient is suffering very severe psychotic or bipolar depression.

• The presence of psychotic features makes hospitalization a consideration.

• The patient's symptoms suggest a complex psychiatric or general medical diagnosis.

• The patient shows persistent psychosocial problems.

• Formal psychotherapy is a consideration.

• Specialized treatments, such as electroconvulsive or light therapy, are a consideration.

• The patient or clinician wishes a second opinion.