Sec. 5
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Outpatient Management of Depression
5 - When to Institute Antidepressant Drug Therapy

If the patient has been evaluated, the diagnosis of major depression confirmed, and the current episode is causing considerable pain and functional impairment (but not so severe as to necessitate hospitalization), the first step is to provide education and support regarding major depression. Then, the question becomes whether to recommend antidepressant medication.

From this author's perspective, the clinician's role should be that of an advisor to the patient, as opposed to dictating any particular treatment plan. Following this philosophy, the clinician should properly assess the patient's complaints and give sufficient information about treatment options so the patient can make an informed decision on his/her own behalf. In the instance where the patient is unable to make such a decision, there are procedural steps (eg, commitment) to follow to ensure that the patient receives proper medical attention; however, that issue is beyond the scope of this book.

The patient may not select the option that the clinician feels is most appropriate. The question then is whether the clinician is comfortable with the patient's choice. If not, further discussion should be pursued or the patient should be referred to a psychiatrist. The underlying philosophy is that the patient should play an active role in the treatment planning. Often, patients will defer to a clinician's judgment, but that is their decision.

This patient-oriented approach has several advantages over a clinician simply telling the patient what needs to be done. Serious illness, such as major depression, often diminishes the patient's self-esteem and confidence. The patient-oriented approach enhances the patient's self-esteem by implicitly communicating to the patient that the clinician values the patient's judgment and wishes. Compliance with the treatment plan is also enhanced by the patient's involvement in the decision-making process.

Using this approach, the clinician needs to explain the treatment options to the patient so that an informed decision can be made about how to proceed. In any area of medicine, proper treatment with any medication involves four major variables, as follow.

The "Four D's"

  • Diagnosis-Does the patient have a condition that will benefit from medication? Factors that need to be considered include:
    - Will the condition persist longer without medication?
    - Is the condition likely to progressively worsen without medication?
    - Will failure to treat with medication result in chronic residual problems or even death?
  • Drug-The selection of the best medication is based on the safety-tolerability-efficacy-payment-simplicity (STEPS) criteria reviewed in Chapters 7 and 8.
  • Dose-What dose will ensure the greatest likelihood of an optimal response in terms of efficacy, tolerability, and safety?
  • Duration-An adequate trial of an antidepressant to induce a remission requires at least 4 weeks on an adequate dose. If there has not been an adequate response by this time, then a decision to switch or augment is needed. An adequate duration for maintenance treatment is a minimum of 4 to 5 months but can be longer depending on:
    - The stage of the illness
    - Specific characteristics of the patient.

Some psychiatrists (this author included) recommend that if a diagnosis of major depression is made, the option of medication therapy should always be considered and offered to the patient. Nevertheless, some patients are reluctant or would prefer not to take medication if possible. Reasons include:

  • The belief that taking antidepressant medication is a "sign of weakness" or "being crazy"
  • Concerns about the medication itself such as:
    - Safety
    - Long-term health consequences
    - Possibility of "addiction"
  • The cost of the medication.

The clinician can resolve many of these concerns through education. Currently available antidepressants are safe as established by extensive clinical trials required by the Food and Drug Administration (FDA) for registration, and by extensive clinical experience with the drugs. Antidepressants are among the most widely prescribed drugs; after only a few years on the market, the cumulative clinical experience with antidepressants often involves literally millions of patients from all walks of life under a wide range of clinical situations (eg, comorbid illnesses and treatments). Antidepressants are not addictive. The patient should not feel that s/he is "weak" or "crazy" for taking an antidepressant, but rather acknowledge that a medical condition exists that should benefit from treatment.

Nonetheless, the patient may legitimately want to know what is the evidence that the antidepressant medications will help. Those answers come from clinical trials done to gain FDA approval for marketing. In these studies, patients with major depression are randomly assigned to receive the new antidepressant, a standard antidepressant, or a placebo in a double-blind fashion (ie, neither the prescriber nor the patient knows which treatment the patient is receiving to minimize biasing the outcome). These trials typically last 6 to 8 weeks of treatment. At the end of the trial, the results are tallied to answer the following three questions:

  • How many patients improved on each treatment and to what extent (ie, full remission, partial response, no response)?
  • What was the incidence of adverse effects on each treatment?
    - How serious were these effects?
    - Did they persist or remit with continued treatment or require discontinuation?
  • Are there any predictors of either beneficial or adverse outcome?

When evaluating results from clinical trials, the clinician should be aware that there are two common ways of reporting the results: response rates and remission rates (Table 5.1). Response rate is generally 10% to 15% higher than the remission rate. A patient who is a responder but has not experienced a full remission has benefited from treatment, but still has residual symptoms.

TABLE 5.1 — What Is “Response” and “Remission” in Major Depression?

Response = 50% reduction in severity of depressive syndrome as measured by a standardized scale (eg, Hamilton Depression Rating Scale).


Remission = A full resolution of the depressive syndrome such that the patient scores in the nondepressed range on such a standardized scale.
TABLE 5.2 — Predictors of Placebo Response in “Depressed” Patients

• Mood symptom only
• Lower severity (< 15) on HDRS
• Shorter duration (< 3 months)
• Shorter interval since episode onset
• Additional psychiatric diagnoses
• Normal neuroendocrine challenge tests (eg, dexamethasone suppression test)

Abbreviations: HDRS, Hamilton Depression Rating Scale, a standardized severity assessment scale.

From such studies conducted over decades, valuable information has emerged about the treatment of major depression. There is a significant benefit to medication in terms of the likelihood of remission of the depressive episode in comparison to placebo. The number of patients who remit on placebo and on antidepressant therapy varies from study to study. The percentage who remit on placebo generally ranges from 20% to 30% versus a remission rate of 45% to 60% on medication. The patient's chance of responding is thus approximately doubled by taking medication.

There are features which predict placebo response (Table 5.2). The clinician can use these features when making treatment recommendations. There are also findings that do not predict placebo response.

Patients with "a reason for being depressed" do not have a higher or a poorer medication response rate than do patients without "a reason." This finding, along with others, casts serious doubts on the usefulness of the concept of a "reactive depression." This term implies etiology (ie, psychosocial stress) which may be entirely spurious. The question is: Does the patient have a major depressive episode? If so, treatment is indicated.

Thus, the recommendation to use medication is based on the presence of a major depressive episode:

  • The longer the episode, the more pressing the need
  • The greater the severity, the more pressing the need
  • The more substantial the family history, the more pressing the need.103

Also of importance is the fact that the decision to institute medication is just that-an empirical medication trial. If the medication produces a significant improvement within a reasonable period of time (eg, 4 weeks) and is well tolerated, then the patient and clinician will not question continuing such treatment. If the medication is not helpful, then it is appropriate to stop it and try another antidepressant as discussed in Chapter 11. Thus, the patient should understand that the decision to try medication is for a specified interval of time after which a decision can be made about whether to continue with it.


TABLE 5.3 — Factors Related to Noncompliance
  • Duration, complexity, and tolerability of regimen
  • Lack of trust
  • Lack of supportive follow-up
  • Perceived mastery over the illness
  • Severity of the illness
  • Doubts about effectiveness
  • Lack of social supports
  • Poor educational background
  • Organicity
  • Concomitant substance abuse

Beyond the "Four D's," patient compliance with the treatment plan is the most important factor in determining outcome of antidepressant therapy. Table 5.3 presents the variables related to noncompliance. The clinician can address and minimize many of these variables through patient education, as discussed in this section and in Chapter 4. The clinician also should determine whether other variables are present, such as:

  • The occurrence of rate-limiting adverse effects
  • Lack of social support
  • The concomitant presence of substance abuse and/or organicity.

If these variables are present, the clinician needs to address them and modify the treatment plan accordingly.

In terms of education, the patient should understand that without effective treatment, the episode may last for many months to even several years. Such a prolonged episode can cause considerable functional impairment, both in the patient's personal life and on the job.

The patient should also understand what is expected from treatment. The goal is full remission of the depressive episode on monodrug therapy. This goal is realistic for a substantial percentage of patients in the primary-care setting.


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