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

Back pain
concentrate, indecisiveness
Significant change in appetite
Excessive or inappropriate guilt
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

70 National Comorbidity
Survey
60 58%
55%
% of Depressed Patients

NIMH Epidemiology
50 Study

40 38% 37%
35%

30 28%
25%

20 17%

10

0
Aches/Pain Aches/Pain Anxiety Disorder Anxiety Disorder
(Women) (Men) (Women) (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.
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

Locus Ceruleus
Raphe Nuclei (NE Source)
(5-HT source)

Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996.

There are at least two sides to the neurotransmitter story
Functional domains of Serotonin and Norepinephrine1-4

Serotonin (5-HT) Depressed

Norepinephrine (NE)
Mood
Sex Concentration
Anxiety

Appetite Vague Aches Interest

and pain

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: 2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge 3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.
University Press 2000. 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 Descending Pathway

spinal cord may explain an Descending
increased pain perception among Pathway Ascending
depressed patients1-3 Pathway

• Imbalances of 5HT and NE may

explain the presence of both
emotional and physical symptoms of Ascending
depression. Pathway

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.
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 Depression
(Major Depressive Disorder)
15
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

Remitted patients virtually equaled healthy controls on

Higher Score
indicates greater
functioning levels at endpoint of 12-week treatment trial
impairment (Responders & non-responders did not)
5
Social Adjustment Scale-SR

3
(Mean ± SD)

*
*
**
2

1
Normal Remission Response Nonresponse
(n=482) (n=202) (n=122) (n=299)
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.
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.