Professional Documents
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Despite the availability of proven treatments, both disorders remain underrecognized and undertreated. Their diagnosis and management are complicated by the considerable overlap of symptomatology. For example, according
to the National Comorbidity Survey,4 58% of those with
lifetime depression were also observed to have at least one
anxiety disorder. Furthermore, increased health care resource utilization and decreased productivity are more significant in patients with comorbid anxiety and depression.3
Anxiety and depression are often manifested initially
as physical ailments rather than the classic symptom of
altered mood; thus, it is not surprising that many of these
patients turn to their primary care physicians for care. As
a result, it is crucial for the generalist physician to be well
versed in recognizing and managing such cases. Now
more than ever, new, more user-friendly pharmacologic
options demonstrate robust efficacy; simplified treatment
with monotherapy can provide the necessary tools to
manage anxiety and depression in the primary care setting both efficaciously and cost effectively. Toward this
end, this article reviews these clinical disorders and summarizes current information on the drug therapies available to treat them.
ANXIETY
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James C. Ballenger
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Co
somnia and anorexia. Data on mirtazapine use in noncomorbid anxiety disorders are limited.
Venlafaxine extended release (XR) is the only agent
with a dual indication for the treatment of depression and
GAD. In addition to demonstrating efficacy in GAD,2126
some data suggest it may be useful in social phobia,27
panic disorder,28 and OCD. 29 Other reports suggest it is
highly effective in the treatment of patients with mixed
anxiety and depression. 30,31 Venlafaxine XR has a low potential for drug-drug interactions,32 which makes it suitable as a first-line agent in these patients, particularly in
those in whom such interactions are more likely.
py
DEPRESSION
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James C. Ballenger
Possible
Does the patient have any of the following symptoms?
presenting
Depressed mood or sadness
symptoms
Decreased energy
Insomnia
Weight loss
Unexplained medical complaint, such as
Chronic pain
Gastrointestinal distress
Dizziness
Step 1
Does the patient have a general medical condition that
may be causing depression, or is it being caused by
substance use (eg, alcohol, illegal drugs, prescription
medications)?
Can the depressed mood be accounted for by another
mental disorder?
Step 2
Has the depressed mood or loss of interest or pleasure
persisted over a 2-week period? If yes, consider
Major depressive disorder, single episode
Major depressive disorder, recurrent
If criteria for major depressive episode are met, is there
a history of elevated, expansive, or euphoric mood?
If yes, consider
Bipolar I disorder
Bipolar II disorder
Step 3
Has the depressed mood been present for most of the
past 2 years in adults (or 1 year in children)? If yes,
consider
Dysthymic disorder
Steps 46
Is the depressed mood associated with any of the
following?
Death of a loved one (consider bereavement)
Identifiable social stressor (consider adjustment
disorder)
Distinct, disabling symptoms that do not meet any
criteria noted above (consider depressive
disorder not otherwise specified)
a
Adapted from the American Psychiatric Association. 41
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from that typically seen in younger patients, often occurring as a consequence of an underlying physical illness or
its treatment or in association with the loss of a spouse.39
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Management of Depression
in the Primary Care Setting
The aggressive and appropriate management of depression in the primary care setting is crucial, not only from a
clinical perspective, but from a health economics perspective as well. Untreated or inadequately treated patients are
more likely to have negative medical consequences of
their depression, including a substantial risk of suicide and
longer, more treatment-resistant episodes of depression.42
Such patients will continue to use valuable health care resources inappropriately, including significantly more general medical services.43
Thus, the challenge for clinicians is to make a rapid and
accurate diagnosis and then to ensure adequate and effec-
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Goal
Duration
Dosage
Complete remission
612 wk
Full
of symptoms
Maintenance
Stabilization of
45 mo
Full
patient (to normal
functioning)
Discontinuation b Prevention of
15 mo
Taper by 25%
relapse
per wk
a
Adapted with permission from Montano.40 Data from Hirschfeld46
and Frank et al.47
b
For patients with severe or recurrent depression, a strong family
history of depression, or signs of suicidal ideation, lifelong full-dosage
therapy should be considered. Antidepressant therapy should not be
discontinued during stressful life events or during the winter in
patients with seasonal affective disorder.
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Generic Name
SSRIs
Citalopram
Celexa
20
2060
Fluoxetine
Prozac
20
2080
Fluvoxamine
Luvox
50
50300
Paroxetine
Paxil
20
2050
Sertraline
Zoloft
50
100200
SNRIs
Venlafaxine IR
Effexor
75
150225
Venlafaxine XR
Effexor XR
75
150225
Atypical antidepressants
Bupropion
Wellbutrin
200
300450
Bupropion SR
Wellbutrin SR
150
300400
Nefazodone
Serzone
200
300600
Mirtazapine
Remeron
15
1545
a
Data from Cohen, 42 Drug Facts and Comparisons,49 and Noble and
Benfield. 48 Abbreviations: IR = immediate-release formulation,
SNRI = serotonin-norepinephrine reuptake inhibitor, SR = sustainedrelease formulation, SSRI = selective serotonin reuptake inhibitor,
XR = extended-release formulation.
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James C. Ballenger
Risk of
Cytochrome P450Based
Activation Drug-Drug Interactions
Co
Drug
Sedation Anticholinergic
SSRIs
Citalopram
0/+
0/+
0/+
0/+
0/+
Fluoxetine
0/+
0/+
0
+
++
Fluvoxamine
0/+
0/+
0
0/+
++
Paroxetine
+
0/+
0
+
+/++
Sertraline
0/+
0/+
0
+
++
SNRIs
Venlafaxine XR
0/+
0/+
0
0/+
0
Atypical
Bupropion
0
0/+
0
+
0/+
Nefazodone
+/++
0/+
+/++
0/+
++
Mirtazapine
+++
0/+
0
0/+
0/+
a
Adapted from Cohen42 and Wells and Mandos. 57 Additional data from Jefferson,56 Dopheide et al.,20
Frazer,44 Noble and Benfield,48 and Danish University Antidepressant Group.50 Abbreviations:
SNRI = serotonin-norepinephrine reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor,
XR = extended-release formulation. Symbols: 0 = none, + = minimal, ++ = moderate, +++ = severe.
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investigators have concluded that these disorders may reflect a continuum of the clinical expression of a single disease. Because patients with chronic anxiety often develop
depressive disorders over time, it also has been hypothesized that anxiety disorders actually may be, in some
cases, a prodrome for depression.59 Contrasting data suggest that GAD, in particular, is an anxiety disorder that
should be considered an independent entity, rather than as
a prodrome, residual, or severity marker of depression.60
Nevertheless, the coexistence of anxiety and depression in
the same patient negatively affects his or her clinical outcome substantially. Such patients typically have more severe manifestations of these illnesses and respond less robustly to treatment than do patients with either disorder
alone.61 Fortunately, with the wide array of new antidepressants available today that can provide robust efficacy, these
patients now have access to new agents that can treat both
mood and anxiety disorders effectively.
In terms of prevalence, it has been more difficult to establish the exact frequency with which these conditions
coexist in the general population because of overlaps in
diagnostic criteria. As many as 10% of patients in the primary care setting may have comorbid anxiety and depression.62 However, as many as 60% of patients with MDD
have moderate anxiety, and 20% to 25% have more severe
anxiety.4,60,61
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DSM-IV Classification of
Mixed Anxiety-Depressive Disorder
Many patients seen in the primary care setting with
manifestations of both anxiety and depression fail to meet
the full criteria for a specific anxiety or depressive disorder. However, it is now recognized that these patients may
have a distinct disorder termed mixed anxiety-depressive
disorder and that the identification of such patients would
be enhanced by the development of specific diagnostic criteria. Thus, the APA has included this provisional category
in DSM-IV. Mixed anxiety-depressive disorder is characterized by a persistent or recurrent dysphoric mood of 4
weeks duration that is accompanied by symptoms of anxiety and depression. Symptoms could include difficulties
with concentration or memory, sleep disturbances, fatigue
or low energy, irritability, or worry, but these fail to meet
criteria for a full anxiety or depressive disorder.63
Patients with elements of both anxiety and depression
but with more specific distress than that exhibited by patients with mixed anxiety-depressive disorder usually can
be distinguished on the basis of the predominant feature
of their syndrome. For example, depressed patients with
comorbid anxiety generally can be identified by the significant absence of a positive affect, with emphasis on anhedonia and hopelessness. In contrast, patients with predominant anxiety and subsymptoms of depression more
often have physiologic symptoms, such as motor tension
and autonomic hyperactivity.63
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1. Rice DP, Miller LS. Health economics and cost implications of anxiety
and other mental disorders in the United States. Br J Psychiatry 1998;173
(suppl 34):49
2. Greenberg PE, Sisitsky T, Kessler RC, et al. The economic burden of anx-
s,
REFERENCES
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CONCLUSIONS
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60.
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