A challenge for the primary-care practitioner is how to efficiently and accurately determine whether a patient is suffering from major depression alone or in combination with a comorbid medical illness (eg, a patient with diabetes mellitus who is also suffering from major depression). This task is even more challenging because there are no confirmatory or screening laboratory tests that are sufficiently sensitive or specific to be clinically useful. Thus, the diagnosis must be based on clinical grounds:

• Medical history
• Physical examination
• Laboratory tests; to rule out other medical conditions that can cause a depressive episode.

The primary presenting picture generally falls into one of four categories:

• Mood or emotional complaints:
  - Low self-esteem or feelings of inadequacy
  - Anxiety
  - Irritability
  - Apathy
  - Loss of interest
• Somatic complaints:
  - Insomnia
  - Fatigue
  - Headache
  - Weight change (loss or gain)
• "Memory" problems
• Life complaints:
  - Inability to cope with marital or job stresses
  - Social withdrawal or isolation
  - Financial problems.

The clinician may unfortunately conclude that the depressive symptoms are understandable results of the patient's life situation and/or recent stressors. While that connection may seem obvious given cultural beliefs, it is often wrong. Major depression may be the cause of the life problems rather than being the result of them. After all, this illness can adversely affect work performance, motivation, and social skills.

Having a "reason" for major depression does not alter its course, reduce its severity and consequences, nor change its responsiveness to treatment. Nonetheless, clinicians may not treat major depression if they perceive that the patient "has a reason for being depressed." However, they would never think of not treating a myocardial infarction or lung carcinoma because the patient has a "reason" for having the illness, such as being overweight or being a smoker, respectively.

Further complicating the diagnostic process is the fact that some patients will deny the mood symptoms of clinical depression, yet present with all the other symptoms (Figure 3.1).

What to Do After the Suspicion of Major Depression Has Arisen

There are many possible medical causes of a depressive episode, which need to be efficiently assessed and ruled out to arrive at a diagnosis of major depression. The diagnostic process can be accomplished by following these steps:

The following series of hierarchically arranged questions is recommended to establish the presence of a depressive episode:

FIGURE 3.1 — Diagnostic and Treatment Planning Process

• Question 1

You have been having problems with [use patient's words] (eg, "depression," "insomnia," "stress at work"). What else have you noticed about how you have been feeling or acting?

This question is phrased to elicit as many spontaneous reports of the signs and symptoms of a depressive episode as possible. The clinician can then follow-up and clarify the patient's answer(s) in terms of duration, clustering, temporal stability, and severity. Frequently, a patient who presents with mood or emotional symptoms will remain fixed on these complaints when asked Question 1. In this case, the clinician can move to the next more focused question.

• Question 2

I understand that you have been feeling [using patient's words] (eg, "depressed," "sad," "hopeless," "overwhelmed"). Has this affected you physically?

This question is designed to shift the patient's mental set to somatic signs and symptoms of major depression (ie, sleep, appetite, energy, activity, sex drive, and concentration/attention). The patient who has major depression will generally report a number of these symptoms at this point. At that point, the clinician can explore duration, clustering, temporal stability, and severity. Based on the answers to this series of questions, the clinician will have gathered sufficient data to have a reasonable opinion as to whether the patient is experiencing a depressive episode. To completely and fully assess the severity of the syndrome, the clinician can then move to highly specific questions, such as:

• Question 3

Since you have been [using patient's words] (eg, "depressed," "bothered by headaches"), have you also been having problems with:

• Mood (being depressed, irritable, anxious)
• Sleep (too little or too much)
• Appetite (too little or too much)
• Energy (subjective)
• Activity (objective)
• Interest
• Motivation
• Concentration/attention
• Sex drive.

If desired, this portion can also be done by having the patient complete a checklist or by having appropriate clinic staff (eg, office nurse) conduct this portion of the interview. If any answers to the questions on this list are positive and represent new findings, further questions may be needed to assess their duration, temporal stability, and severity, and whether they have occurred as a cluster with any other previously elicited depressive symptoms.

By using these three questions, the clinician can evaluate whether the patient fulfills criteria for a depressive syndrome. Most often, the diagnosis will be major depression. Nonetheless, a depressive syndrome can be due to several other causes. Hence, the clinician needs to rule out other possibilities.

Work-Up for Other Causes of a Depressive Syndrome

(Table 3.1)

• Medical history and physical examination-the clinician can assess for a variety of other medical causes of major depression
• History of present illness-be alert for any signs of symptoms that are not typically associated with major depression (eg, productive cough)
• Past medical history-are there any past illnesses that could be recurrent and cause a depressive syndrome?
• Medications-is the patient taking any medications (eg, antihypertensives, steroids) which could cause a depressive syndrome?
• Social history-is the patient drinking alcohol or abusing illicit drugs?
• Family history-are there other family members with major depression or other psychiatric disorders that could be presenting as a
  depressive syndrome? Remember most psychiatric illnesses run in families. The family history therefore can help elucidate and support the diagnosis. Conditions such as somatization disorder (eg, Briquet's syndrome) can present with waxing and waning complaints of dysphoria and anxiety and lead to a false-positive diagnosis of major depression. Somatization disorders tend to run in families, so check whether other relatives (particularly females) have complicated medical histories. A family history of bipolar disorder increases the likelihood that the patient will eventually have a manic episode, and treatment with a mood stabilizer (eg, lithium) might be warranted, either alone or in combination with an antidepressant (Chapter 11).
• Physical observation-the patient with major depression typically will have the following findings (Figure 3.1 and Table 3.2):
  - Diminished eye contact
  - Sad, apathetic, or emotionally blunted expression
  - Stooped posture
  - Decreased rate and rhythm of speech
  - Increased latency of response.
  Less often, patients will show:
  - Irritability
  - Psychomotor restlessness (eg, drumming fingers, biting nails). The efficient clinician can assess the mental status while obtaining the history and will also be comparing the patient's subjective statements about the severity of the patient's condition with observations of behavior during the interview.
• Laboratory tests-the standard laboratory work-up is to evaluate other possible medical causes. These tests include:
  - Complete blood cell count
  - Liver, renal, and thyroid function tests
  - Urinalysis
  - Serology for infectious diseases (if the history warrants). Other laboratory tests would be more patient specific, such as an electrocardiogram, depending on the age of the patient, or brain imaging if a neurological condition needs to be assessed.

For the primary-care clinician who has treated the patient for some time, the above history may either already be known or can be quickly elicited. If that is not the case, then the clinician or a staff member can obtain that information at either the initial or a follow-up visit. That decision should be based on the clinician's assessment of how likely it is that this information would substantially alert his/her opinion and course of treatment.

Note: The above has focused on differential diagnosis and thus has discussed major depression and other medical conditions from an "either/or" perspective. In fact, clinical depression is frequently comorbid with a variety of other medical illnesses (eg, cancer, diabetes, coronary artery disease). In such instances, both conditions need to be treated for optimal outcome. Otherwise, untreated clinical depression can seriously compromise the ability to effectively treat the whole patient. This fact also means the clinician needs to be mindful of the potential for interactions between the various medications the patient will be taking. This issue and its relevance to antidepressant drug selection is discussed in greater detail in Chapters 6 and 10.

To Treat or Not to Treat Now?

If the severity of the syndrome is mild and/or not convincingly present, the clinician may decide to defer initiating antidepressant pharmacotherapy and schedule the patient for a follow-up within 1 week. This approach permits an assessment of the temporal stability of the patient's complaints. That is particularly true if somatization disorder is suspected because depressive and anxiety complaints in such patients may be prominent one week and gone the next.

Conversely, if the illness is sufficiently severe to be causing distress and/or dysfunction, the prescriber may elect to start a trial of medication, and schedule a follow-up visit in 1 week. Chapters 6 through 9 provide a way of evaluating which antidepressant is likely to be the best option for a specific patient.