TITLE:
Practice guideline for the treatment of patients with major depressive
disorder.
SOURCE(S):
Am J Psychiatry 2000 Apr;157(4 Suppl):1-45. [325 references]
ADAPTATION:
Not applicable: Guideline was not adapted from another source.
RELEASE DATE:
1993 (revised 2000)
MAJOR RECOMMENDATIONS:
Each recommendation is identified as falling into one of three categories of
endorsement, by a bracketed Roman numeral following the statement. The three
categories represent varying levels of clinical confidence regarding the
efficacy of the treatment for the disorder and conditions described.
[I] indicates recommended with substantial clinical confidence.
[II] indicates recommended with moderate clinical confidence.
[III] indicates options that may be recommended on the basis of individual
circumstances.
Successful treatment of patients with major depressive disorder is promoted
by a thorough assessment of the patient [I]. Treatment consists of an acute
phase, during which remission is induced; a continuation phase, during which
remission is preserved; and a maintenance phase, during which the
susceptible patient is protected against the recurrence of subsequent major
depressive episodes. Psychiatrists initiating treatment for major depressive
disorder have at their disposal a number of medications, a variety of
psychotherapeutic approaches, electroconvulsive therapy (ECT), and other
treatment modalities (e.g., light therapy) that may be used alone or in
combination. The psychiatrist must determine the setting that will most
likely ensure the patient's safety as well as promote improvement in the
patient's condition [I].
A.   Psychiatric Management
Psychiatric management consists of a broad array of interventions and
activities that should be instituted by psychiatrists for all patients with
major depressive disorder [I]. Regardless of the specific treatment
modalities selected, it is important to continue providing psychiatric
management through all phases of treatment. The specific components of
psychiatric management that must be addressed for all patients include
performing a diagnostic evaluation, evaluating safety of the patient and
others, evaluating the level of functional impairments, determining a
treatment setting, establishing and maintaining a therapeutic alliance,
monitoring the patient's psychiatric status and safety, providing education
to patients and families, enhancing treatment adherence, and working with
patients to address early signs of relapse.
B.    Acute Phase
1.     Choice of an initial treatment modality
In the acute phase, in addition to psychiatric management, the psychiatrist
may choose between several initial treatment modalities, including
pharmacotherapy, psychotherapy, the combination of medications plus
psychotherapy, or electroconvulsive therapy [I]. Selection of an initial
treatment modality should be influenced by both clinical (e.g., severity of
symptoms) and other factors (e.g., patient preference).
a.      Antidepressant medication
If preferred by the patient, antidepressant medications may be provided as
an initial primary treatment modality for mild major depressive disorder
[I]. Antidepressant medications should be provided for moderate to severe
major depressive disorder unless electroconvulsive therapy is planned [I]. A
combination of antipsychotic and antidepressant medications or
electroconvulsive therapy should be used for psychotic depression [I].
b.     Psychotherapy
A specific, effective psychotherapy alone as an initial treatment modality
may be considered for patients with mild to moderate major depressive
disorder [II]. Patient preference for psychotherapeutic approaches is an
important factor that should be considered in the decision. Clinical
features that may suggest the use of psychotherapeutic interventions include
the presence of significant psychosocial stressors, intrapsychic conflict,
interpersonal difficulties, or a comorbid axis II disorder [I].
c.     Psychotherapy plus antidepressant medications
The combination of a specific effective psychotherapy and medication may be
a useful initial treatment choice for patients with psychosocial issues,
interpersonal problems, or a comorbid axis II disorder together with
moderate to severe major depressive disorder [I]. In addition, patients who
have had a history of only partial response to adequate trials of single
treatment modalities may benefit from combined treatment. Poor adherence
with treatments may also warrant combined treatment modalities.
d.     Electroconvulsive therapy
Electroconvulsive therapy should be considered for patients with major
depressive disorder with a high degree of symptom severity and functional
impairment or for cases in which psychotic symptoms or catatonia are present
[I]. Electroconvulsive therapy may also be the treatment modality of choice
for patients in whom there is an urgent need for response, such as patients
who are suicidal or refusing food and nutritionally compromised [II].
2.     Choice of specific pharmacologic treatment
Antidepressant medications that have been shown to be effective are listed
in the full-text guideline document -- see the table titled "Commonly Used
Antidepressant Medications" [II]. The effectiveness of antidepressant
medications is generally comparable between classes and within classes of
medications. Therefore, the initial selection of an antidepressant
medication will largely be based on the anticipated side effects, the safety
or tolerability of these side effects for individual patients, patient
preference, quantity and quality of clinical trial data regarding the
medication, and its cost (for more information, see Section V.A.1 of the
original guideline document) [I]. On the basis of these considerations, the
following medications are likely to be optimal for most patients: selective
serotonin reuptake inhibitors (SSRIs), desipramine, nortriptyline,
bupropion, and venlafaxine. In general, monoamine oxidase inhibitors (MAOIs)
should be restricted to patients who do not respond to other treatments
because of their potential for serious side effects and the necessity of
dietary restrictions. Patients with major depressive disorder with atypical
features are one group for whom several studies suggest monoamine oxidase
inhibitors may be particularly effective; however, in clinical practice,
many psychiatrists start with selective serotonin reuptake inhibitors in
such patients because of the more favorable adverse effect profile.
a.      Implementation
When pharmacotherapy is part of the treatment plan, it must be integrated
with the psychiatric management and any other treatments that are being
provided (e.g., psychotherapy) [I]. Once an antidepressant medication has
been selected, it can be started at the dose levels suggested in the
full-text guideline document -- see the table titled "Commonly Used
Antidepressant Medications" [I]. Titration to full therapeutic doses
generally can be accomplished over the initial week(s) of treatment but may
vary depending on the development of side effects, the patient's age, and
the presence of comorbid illnesses. Patients who have started taking an
antidepressant medication should be carefully monitored to assess their
response to pharmacotherapy as well as the emergence of side effects,
clinical condition, and safety [I] (see "Management of Medication Side
Effects" in the original guideline document.). Factors to consider in
determining the frequency of patient monitoring include the severity of
illness, the patient's cooperation with treatment, the availability of
social supports, and the presence of comorbid general medical problems.
Visits should also be frequent enough to monitor and address suicidality and
to promote treatment adherence. In practice, the frequency of monitoring
during the acute phase of pharmacotherapy can vary from once a week in
routine cases to multiple times per week in more complex cases.
b.     Failure to respond
If at least moderate improvement is not observed following 6-8 weeks of
pharmacotherapy, a reappraisal of the treatment regimen should be conducted
[I]. Section II.B.2.b in the original guideline document reviews options for
adjusting the treatment regimen when necessary. Following any change in
treatment, the patient should continue to be closely monitored. If there is
not at least a moderate improvement in major depressive disorder symptoms
after an additional 6-8 weeks of treatment, the psychiatrist should conduct
another thorough review. An algorithm depicting the sequence of subsequent
steps that can be taken for patients who fail to respond fully to treatment
is provided in the full-text guideline document --see "Acute Phase Treatment
of Major Depressive Disorder."
3.     Choice of specific psychotherapy
Cognitive behavioral therapy and interpersonal therapy are the
psychotherapeutic approaches that have the best documented efficacy in the
literature for the specific treatment of major depressive disorder, although
rigorous studies evaluating the efficacy of psychodynamic psychotherapy have
not been published [II]. When psychodynamic psychotherapy is used as a
specific treatment, in addition to symptom relief, it is frequently
associated with broader long-term goals. Patient preference and the
availability of clinicians with appropriate training and expertise in the
specific approach are also factors in the choice of a particular form of
psychotherapy.
a.      Implementation
When psychotherapy is part of the treatment plan, it must be integrated with
the psychiatric management and any other treatments that are being provided
(e.g., medication treatment) [I]. The optimal frequency of psychotherapy has
not been rigorously studied in controlled trials. The psychiatrist should
take into account multiple factors when determining the frequency for
individual patients, including the specific type and goals of psychotherapy,
the frequency necessary to create and maintain a therapeutic relationship,
the frequency of visits required to ensure treatment adherence, and the
frequency necessary to monitor and address suicidality. The frequency of
outpatient visits during the acute phase generally varies from once a week
in routine cases to as often as several times a week. Regardless of the type
of psychotherapy selected, the patient's response to treatment should be
carefully monitored [I].
If more than one clinician is involved in providing the care, it is
essential that all treating clinicians have sufficient ongoing contact with
the patient and with each other to ensure that relevant information is
available to guide treatment decisions [I].
b.     Failure to respond
If after 4-8 weeks of treatment at least a moderate improvement is not
observed, then a thorough review and reappraisal of the diagnosis,
complicating conditions and issues, and treatment plan should be conducted
[I]. Figure 3 and Section II.B.3.b. in the original guideline document
review the options to consider.
4.     Choice of medications plus psychotherapy
In general, the same issues that influence the specific choice of medication
or psychotherapy when used alone should be considered when choosing
treatments for patients receiving combined modalities [I].
5.     Assessing the adequacy of response
It is not uncommon for patients to have a substantial but incomplete
response in terms of symptom reduction or improvement in functioning during
acute phase treatments. It is important not to conclude the acute phase of
treatment for such patients, as a partial response is often associated with
poor functional outcomes. When patients are found to have not fully
responded to an acute phase treatment, a change in treatment should be
considered as outlined in the full-text guideline document -- see "Acute
Phase Treatment of Major Depressive Disorder" [II].
C.   Continuation Phase
During the 16-20 weeks following remission, patients who have been treated
with antidepressant medications in the acute phase should be maintained on
these agents to prevent relapse [I]. In general, the dose used in the acute
phase is also used in the continuation phase. Although there has been less
study of the use of psychotherapy in the continuation phase to prevent
relapse, there is growing evidence to support the use of a specific
effective psychotherapy during the continuation phase [I]. Use of
electroconvulsive therapy in the continuation phase has received little
formal study but may be useful in patients for whom medication or
psychotherapy has not been effective in maintaining stability during the
continuation phase [II]. The frequency of visits must be determined by the
patient's clinical condition as well as the specific treatments being
provided.
D.   Maintenance Phase
Following the continuation phase, maintenance-phase treatment should be
considered for patients to prevent recurrences of major depressive disorder
[I]. Factors to consider are discussed in the full-text guideline
document -- see the table titled "Considerations in the Decision to Use
Maintenance Treatment" -- and Section II.D of the original guideline
document.
In general, the treatment that was effective in the acute and continuation
phases should be used in the maintenance phase [II]. In general, the same
full antidepressant medication doses are employed as were used in prior
phases of treatment; use of lower doses of antidepressant medication in the
maintenance phase has not been well studied. For cognitive behavioral
therapy and interpersonal therapy, maintenance phase treatments usually
involve a decreased frequency of visits (e.g., once a month). The frequency
of visits in the maintenance phase must be determined by the patient's
clinical condition as well as the specific treatments being provided. The
frequency required could range from as low as once every 2-3 months for
stable patients who require only psychiatric management and medication
monitoring to as high as multiple times a week for those in whom
psychodynamic psychotherapy is being conducted.
E.    Discontinuation of Active Treatment
The decision to discontinue active treatment should be based on the same
factors considered in the decision to initiate maintenance treatment,
including the probability of recurrence, the frequency and severity of past
episodes, the persistence of dysthymic symptoms after recovery, the presence
of comorbid disorders, and patient preferences [I]. In addition to the
factors listed in the full-text guideline document -- see the table titled
"Considerations in the Decision to Use Maintenance Treatment" and the table
titled "Risk Factors for Recurrence of Major Depressive Disorder" --
patients and their psychiatrists should consider the patient's response, in
terms of both beneficial and adverse effects, to maintenance treatments.


Edward E. Rylander,M.D.
    D.A.B.F.P. AND D.A.B.P.M.