Depression—There are at least two sides to every story.

Depression. It’s not only a state of mind.

Reference: Adapted fromAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition,Text Revision. Washington, DC; American Psychiatric Association. 2000:345-356,489.

The symptoms of depression

Emotional Symptoms Include:

Sadness

Loss of interest or pleasure

Overwhelmed

Anxiety

Diminished ability to think or concentrate, indecisiveness

Excessive or inappropriate guilt

Physical Symptoms Include:

Vague aches and pains

Headache

Sleep disturbances

Fatigue

Back pain

Significant change in appetite resulting in weight loss or gain

Reference:1. Simon GE, et al. N Engl J Med. 1999;341(18):1329-1335.

Depression – the physical presentationIn primary care, physical symptoms are often

the chief complaint in depressed patients

N = 1146 Primary care patients with major depression

In a New England Journal of Medicine study, 69% of diagnosed depressed patients reported unexplained physical symptoms as their chief compliant1

Adapted from 1.Silverstein B. Am J Psychiatry. 1999;156(3):480-482. 2.Silverstein B. Am J Psychiatry. 2002;159(6):1051-1052.

25%

17%

58%

37%

55%

38%35%

28%

0

10

20

30

40

50

60

70

Aches/Pain(Women)

Aches/Pain (Men)

Anxiety Disorder(Women)

Anxiety Disorder (Men)

% o

f D

epre

ssed

Pat

ien

ts

National ComorbiditySurvey

NIMH EpidemiologyStudy

Aches/pain – a physical symptom of significance

Aches/Pain as common as anxiety among depressed patients

• 76% of compliant depressed patients with lingering symptoms of depression relapsed within 10 months1*

The importance of emotional and physical symptoms

*Psychiatric inpatients and outpatients.

Reference:1. Adapted from: Paykel ES, et al. Psychol Med. 1995;25:1171-1180.

94% of depressed patients who experienced lingering symptoms had mild to moderate physical symptoms1

Serotonin5HT and NorepinephrineNE in the brain

Limbic System

Locus Ceruleus (NE Source)

Prefrontal Cortex

Raphe Nuclei (5-HT source)

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

There are at least two sides to the neurotransmitter story

Sex

Appetite

Aggression

Concentration

Interest

Motivation

Depressed Mood

Anxiety

Irritability

Thought process

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.

Norepinephrine (NE)

• Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms

Serotonin (5-HT)

Vague Aches and pain

Functional domains of Serotonin and Norepinephrine1-4

The neurotransmitter pathway story

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.

• 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.

It’s not all in your head

Descending Pathway

Ascending Pathway

AscendingPathway

DescendingPathway

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*

References:1. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640.

* Antidepressant clinical drug trials.

Response and Remission defined

Hamilton Depression Rating Scale (HAM-D): 17 Items, Total Score 0 - 52

15

7

Response 50% reduction from baseline HAM-D

score

Remission: HAM-D Score 7

Depression (Major Depressive Disorder)

References:1. Frank E. Conceptualization and rationale for consensus definition terms in MDD, Arch Gen Psych. 1991; 48:851-855.

HAM-D17 Scores

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.

Normal(n=482)

Remission (n=202)

Response(n=122)

Nonresponse(n=299)

Soci

al A

djus

tmen

t Sca

le-S

R

(Mea

n ±

SD)

***

*

1

2

3

5

Treatment outcome:Effect on work & social functioning

Higher Score indicates greater

impairment

Remitted patients virtually equaled healthy controls on functioning levels at endpoint of 12-week treatment trial

(Responders & non-responders did not)

Many depressed patients are still depressed.

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.

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.

*In antidepressant clinical drug trials.