DepressionThere are at least two sides to every story.

Depression. Its not only a state of mind.

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: 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 NIMH Epidemiology Study

% of Depressed Patients

60 50 40 30 20 10 0 25%

55%

58%

38%

35%

37% 28%

17%

Aches/Pain (Women)

Aches/Pain (Men)

Anxiety Disorder Anxiety Disorder (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

Raphe Nuclei (5-HT source)

Locus Ceruleus (NE 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)
Sex
Appetite Aggression

Depressed Mood Anxiety Vague Aches and pain Irritability Thought process

Norepinephrine (NE)
Concentration Interest Motivation

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

Its 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. OReardon 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 7

Depression (Major Depressive Disorder)

Response 50% reduction from baseline HAM-D score 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

Higher Score indicates greater impairment

Social Adjustment Scale-SR (Mean SD)

5 3

Remitted patients virtually equaled healthy controls on functioning levels at endpoint of 12-week treatment trial (Responders & non-responders did not)

* **

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