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Depression—There are at least two sides to
every story.
Depression. It’s not only a state of mind.
The symptoms of depression
Emotional Symptoms Include:
Physical Symptoms Include:
Sadness
Vague aches and pains
Loss of interest or pleasure
Headache
Overwhelmed
Sleep disturbances
Anxiety
Fatigue
Diminished ability to think or
concentrate, indecisiveness
Back pain
Excessive or inappropriate guilt
Significant change in appetite
resulting in weight loss or gain
Reference: Adapted from
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.
Fourth Edition,Text Revision. Washington, DC; American Psychiatric Association. 2000:345-356,489.
Depression – the physical presentation
In primary care, physical symptoms are often
the chief complaint in depressed patients
In a New England Journal of Medicine
study, 69% of diagnosed depressed
patients reported unexplained physical
symptoms as their chief compliant1
N = 1146 Primary care patients with major depression
Reference:
1. Simon GE, et al. N Engl J Med. 1999;341(18):1329-1335.
Aches/pain – a physical symptom of significance
Aches/Pain as common as anxiety among depressed patients
% of Depressed Patients
70
60
National Comorbidity
Survey
58%
55%
NIMH Epidemiology
Study
50
38%
40
30
35%
37%
28%
25%
17%
20
10
0
Aches/Pain
(Women)
Aches/Pain
(Men)
Adapted from
1.Silverstein B. Am J Psychiatry. 1999;156(3):480-482.
2.Silverstein B. Am J Psychiatry. 2002;159(6):1051-1052.
Anxiety Disorder Anxiety Disorder
(Women)
(Men)
The importance of emotional and physical symptoms
• 76% of compliant depressed
patients with lingering
symptoms of depression
relapsed within 10 months1*
94% of depressed
patients who experienced
lingering symptoms had
mild to moderate
physical symptoms1
*Psychiatric inpatients and outpatients.
Reference:
1. Adapted from: Paykel ES, et al. Psychol Med. 1995;25:1171-1180.
Serotonin5HT and NorepinephrineNE in the brain
Limbic System
Prefrontal
Cortex
Raphe Nuclei
(5-HT source)
Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996.
Locus Ceruleus
(NE Source)
There are at least two sides to the neurotransmitter story
Functional domains of Serotonin and Norepinephrine1-4
Serotonin (5-HT)
Sex
Depressed
Mood
Anxiety
Norepinephrine (NE)
Concentration
Appetite
Vague Aches
and pain
Interest
Aggression
Irritability
Motivation
Thought
process
• Both serotonin and norepinephrine mediate a broad spectrum
of depressive symptoms
References:
1. Adapted from: Stahl SM. In: Essential Psychopharmacology:
Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge
University Press 2000.
2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.
4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
The neurotransmitter pathway story
It’s not all in your head
• Dysregulation of Serotonin (5HT)
and Norepinephrine (NE) in the brain
are strongly associated with
depression
• Dysregulation of 5HT and NE in the
spinal cord may explain an
increased pain perception among
depressed patients1-3
• Imbalances of 5HT and NE may
explain the presence of both
emotional and physical symptoms of
depression.
Adapted from References:
1. Stahl SM. J. Clin Psych. 2002;63:203-220.
2. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
3. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
Descending Pathway
Descending
Pathway
Ascending
Pathway
Ascending
Pathway
Depression: Current treatment outcomes1
• Up to 70% of depressed patients respond ( 50%
decrease in HAM-D score) to treatment but fail to
achieve remission from their emotional and physical
symptoms1*
• Approximately 30% of depressed patients achieve
remission ( 7 score on the HAM-D) with treatment1*
*
Antidepressant clinical drug trials.
References:
1. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640.
Response and Remission defined
Hamilton Depression Rating Scale (HAM-D): 17 Items, Total Score 0 - 52
HAM-D17
Scores
15
Depression
(Major Depressive Disorder)
Response
  50% reduction from baseline HAM-D
score
7
Remission: HAM-D Score  7
References:
1. Frank E. Conceptualization and rationale for consensus definition terms in MDD, Arch Gen Psych. 1991; 48:851-855.
Treatment outcome:Effect on work & social functioning
Social Adjustment Scale-SR
(Mean ± SD)
Higher Score
indicates greater
impairment
5
Remitted patients virtually equaled healthy controls on
functioning levels at endpoint of 12-week treatment trial
(Responders & non-responders did not)
3
*
**
2
*
1
Normal
(n=482)
Study in chronic depressed patients
*p.05 vs nonresponse. **p.05 vs response.
Miller IW, et al. J Clin Psychiatry. 1998;59(11):608-619.
Remission
(n=202)
Response
(n=122)
Nonresponse
(n=299)
Many depressed patients are still depressed.
Depressed patients continue to have needs that are not being fully addressed1
• Depressed patients present with emotional and physical
symptoms.
• Approximately 30% of depressed patients achieve
remission in clinical trials2*
• Up to 70% of patients who respond fail to remit2*
• Incomplete relief from symptoms may increase the risk
of relapse2,3
• Lingering emotional and physical symptoms may
jeopardize achieving remission.
References:
1. Nierenberg AA, et al. J Clin Psychiatry. 1999:60(suppl 22):7-11.
2. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640.
3. Lynch ME. J Psychiatry Neurosci. 2001;26(1):30-36.
*In antidepressant clinical drug trials.

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