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Outpatient Management of Depression
5 - When to Institute Antidepressant Drug Therapy |
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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).
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Remission = A full
resolution of the depressive syndrome such that
the patient scores in the nondepressed range on
such a standardized scale. |
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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)
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Abbreviations: HDRS, Hamilton
Depression Rating Scale, a standardized severity
assessment scale. |
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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
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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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