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Total Healthcare of Michigan, P'C'

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Title: Total Healthcare of Michigan, P'C'


1
Total Healthcare of Michigan, P.C.
Chronic Illness Diabetes and Devastating
Depression
  • 2900 Hannah Boulevard, Suite 200East Lansing, MI
    48823
  • Phone (517) 332-0440

2
Chronic Illness Diabetes and Devastating
Depression
3
Chronic Illness Diabetes and Devastating
Depression
  • Anderson at al, Diabetes Care 24 1069 1078,
    2001
  • 39 Studies
  • N 20,218

4
Chronic Illness Diabetes and Devastating
DepressionResults
  • Diabetes.
  • Diabetics have 2 times the risk for depression
    than non-diabetics
  • Women gt Men prevalence
  • 13 women had depression
  • Impaired.
  • Level of functioning
  • Quality of life
  • Adherence to medical treatment, therefore,
    impaired glycemic control
  • Increased
  • Risk of diabetes complications

5
Chronic Illness Diabetes and Devastating
DepressionProspective Studies
  • Depression a risk factor for Type II
    Diabetes
  • Treatment of Major Depression Disorder, increased
    glycemic control
  • However, only 1 in 3 cases are treated for
    depression
  • An increase in HGB1AC (with psych hx) Cohen et
    al 1977
  • Treatment of Depression decreased HGB1AC
    Hustman et al 1997
  • Source General Hospital Psychiatry 1997 Psycho
    Med1997

6
Chronic Illness Diabetes and Devastating
DepressionHMO Statistics
  • Chronic Medical/MDD 24.7
  • No Medical/MDD 17.5
  • Diabetes/MDD 22.7
  • (Wells et al AMJP 1988)
  • Diabetes with MDD showed increased
  • Visits to PCP
  • Visits to ER
  • (Diabetes Care 2003 26 104-111)

7
Leading Causes of Disease Burden for Women in
the US in 1996
Also includes other degenerative and hereditary
CNS disorders Michaud CM., et al. JAMA.
2001285535-539
8
Common Presenting Somatic Complaints in Patients
with Depression
  • Tired all the time, blahs
  • Sexual dysfunction or loss of sexual interest
  • Vague abdominal or joint pains
  • Disturbed sleep
  • Headache
  • Stressed out
  • Malaise
  • GI complaints (i.e., constipation, diarrhea)

DSM-IV-TR Washington DC American Psychiatric
Association 2000. Mulsant, BH, Ganguli M. J Clin
Psychiatry. 1999 60(suppl 20)9-15.
9
Common Presenting Psychological Symptoms in
Patients with Depression
  • Hopelessness
  • Low self-esteem
  • Impaired memory
  • Difficulty
  • Anhedonia
  • Anxiety
  • Preoccupation with negative thoughts

DSM-IV-TR Washington DC American Psychiatric
Association 2000. Mulsant, BH, Ganguli M. J Clin
Psychiatry. 1999 60(suppl 20)9-15.
10
Chronic Nonmalignant Pain (CNP)
  • Myofacial Pain
  • Low Back Pain
  • Muscle Contraction (tension) Headaches
  • Fibromyalgia
  • Nerve Injury Pain
  • Neuropathic Pain
  • Complex Regional Pain Syndrome (SMP)
  • Headaches
  • Arthritis

11
The Cost of Chronic Nonmalignant Pain to the
U.S. Economy
  • 90-100 Billion per Year
  • Direct costs of care
  • Lost productivity
  • Absenteeism
  • Quality of Life for Pain Suffers
  • Inability to work and recreate
  • Loss Function
  • Decrease perception of self worth

12
Economics of Depression Dimensions
Quality of Life
Workplace Impact
Burden of Illness
DEPRESSION
Comparative Data
Cost of Drug Therapy
Cost of Therapy Failure
13
Impact of Untreated Depression
  • Morbidity
  • Comorbid medical illness
  • Suicide attempts
  • Accidents
  • Mortality
  • 35,000 suicides per year
  • Fatal accidents
  • Death due to related illness (substance abuse)
  • Societal and Functional Burdens
  • Dysfunctional families
  • Divorce
  • Substance abuse
  • Absenteeism
  • Decreased productivity
  • Job-related injuries
  • Lost jobs
  • Failure to advance in career or school

Preskorn, 1999
14
Depression May Worsen Outcomes of Many General
Medical Conditions
Depression also may worsen outcomes of cancer,
diabetes, AIDS, and other disorders7
1. Frasure-Smith N, et al. JAMA.
19932701819-1825. 2. Penninx BW, et al. Arch
Gen Psychiatry. 200158221-227. 3. Jiang W, et
al. Arch Intern Med. 20011611849-1856. 4.
Vaccarino V, et al. J Am Coll Cardiol.
200138199-205.
5. Rovner BW, et al. JAMA. 1991265993-996. 6.
Pohjasvaara T, et al. Eur J Neurol.
20018315-319. 7. Petitto JM, Evans DL. Depress
Anxiety. 19988(suppl 1)80-84.
15
Psychoanalysis and Pain
  • Pain referred to as somatization
  • Pain is a symbol of emotional conflict
  • Pain subsides as patient works through
    psychological conflicts in psychotherapy

16
JACHO 2001Revised Standards for Pain Management
  • Patients rights
  • Assessment of pain
  • Care of patients
  • Education of patient and family
  • Continuum of care
  • Improved organizational performance

http//www.jcaho.org.
17
Two Thalamic Pain Outflows
  • Sensory Cortex
  • Location of pain
  • Affective context
  • Limbic System
  • Hedonic aspect of pain
  • Poorly localized
  • Causes agony suffering

18
Emotions and Pain
  • Negative Emotions Increase Pain
  • Sadness
  • Anger
  • Fear
  • Positive Emotions Decrease Pain
  • Joy
  • Humor
  • Sexual arousal

Unrelieved chronic pain often leads to depression
and anxiety
19
Neuropathic Pain
  • Pain that originates in or is amplified by the
    CNS or direct injury to peripheral nerves
  • Often has an emotional component
  • Has a peculiar burning and aching quality
  • Less responsive to opioids

20
Referred Pain Spinal Level
  • Somatic visceral afferents converge on a single
    dorsal horn neuron (e.g., left arm, heart)
  • Neurons sensitized by repetitive pain inputs from
    one source may respond as if all their inputs
    were activated
  • Severe pain input from heart can cause left arm
    pain

21
Referred Pain Limbic Level
  • Limbic neurons sensitized by ascending
    nociceptive pain signals may produce a wider
    range of negative affective states
  • Sustained, intense negative affective states may
    sensitize limbic neurons and create sensations
    of physical pain in the absence of peripheral
    nociception

22
Central Sensitization
  • Repeated negative inputs
  • Kindling
  • Neuroplasticity
  • Remodeling
  • Axonal sprouting

23
Sensitization
10
Injury
Normal Pain Response
8
6
Pain Intensity
Hyperalgesia heightened sense of pain to
noxious stimuli Allodynia pain resulting from
normally painless stimuli
4
2
0
Stimulus Intensity
23
Gottschalk, Smith. Am Fam Physician.
2001631979-1984.
24
Risk Factors for Depression
Loss of a parent before age 10 y
Loss support system of social
Erectile dysfunction
Low levels of testosterone
Infertility
Risk Factors
Social or economic change
Childhood hx physical or sexual abuse
Family hx mood disorders
Personal hx of mood disorders in early
reproductive years
Persistent psychosocial stressors
Risk factors that are greater for or specific
to women. Risk factors that are greater for or
specific to men. Pajer K. J Clin Psychiatry.
199556(suppl2)30-37
Seidman SN, Walsh BT. Am J Geriatr Psychiatry.
1999718-33 ACOG. Int J Gynecol Obstet.
199343203-211 Morgan H. Aust Fam Physician.
200130206-211
25
Theoretical Contributions ofNature and Nurture
to Pathology
Developmental trajectory
Genetic factors
Enriched environment
Vulnerability and resistance genes
Phenotypic plasticity
Social support
Psychiatric intervention
Trauma
Anxiety disorder PTSD-like syndrome Substance
Abuse
HPA axis dysfunction Psycho-immune
disease Depression-like
syndrome
Vulnerability
Long-term (mal)-adaptation
Adapted from Plotsky PM, et al. Psychitr Clin
North Am. 199821293-307.
26
Gender-Specific Differences in Depression
Parameters
Differences in Women vs Men
  • Seasonal effect on mood Greater1
  • Association with stressful More frequent2
  • life events
  • Atypical symptoms of depression More common2
    (i.e., hypersomnia, hyperphagia)
  • Suicidal behavior
  • Suicide attempt More
    frequent3
  • Completed suicide Less frequent3

1. Leibenluft E, et al. Depression. 1995313-19
2. Pajer K. J Clin Psychiatry.
199556(suppl2)30-37 3. Hirschfeld RM,
Russel, JM. N Engl J Med. 1997337910-915
27
Mortality From NSAID Induced GI
ComplicationsVersus Other Diseases in United
States
25,000 20,000 15,000 10,000 5,000
0
20,197
16,685 16,500
10,503
Number of Deaths
5,338
4,441
1,437
Leukemia1 HIV NSAIDs Multiple Asthma1
Cervical Hodgkins
GI2 Myleoma1
Cancer Disease
Cause of Death
  • Data from 1997 Estimated
  • National Center for Health Statistics, 1998
  • Singh G, et al. J Rheumatol. 199926 (Suppl
    56)18-24

28
COX-2 and Peripheral Mechanisms of Pain
EP receptor
PKA PKCe
PGE2
Resting Membrane Potential Increases
SNS/PN3 TTX-resistant sodium channel
Neuron FiringThreshold Decreases
Samad et al. Nature. 2001410471-475 Woolf,
Salter. Science. 20002881765-1769Byers,
Bonica. In Bonicas Management of Pain.
200127-72.
29
Pathophysiology of COX-1, COX-2, and COX-3
Arachidonic Acid
30
Arthritis Pain Management Key Recommendations
Common to the APS, ACR, and AGS Guidelines
  • Start with acetaminophen because of cost,
    efficacy, and low toxicity
  • COX-2s for those at risk of GI complications or
    those who require long-term, daily analgesic
    therapy AGS 2002
  • Non-selective NSAIDs GI risk assessment and use
    of cytoprotective agents
  • Opioids for severe pain or pain not controlled by
    APAP and/or COX-2s
  • APSAmerican Pain Society ACRAmerican College
    of Rheumatology AGSAmerican Geriatric Society.
  • Adapted from American Pain Society, 2002 ACR
    Subcommittee on OA Guidelines. Arthritis Rheum.
    2000431905-1915 Adapted from American
    Geriatric Society, 2002.

31
Malalignment
From the Clinical Slide Collection on the
Rheumatic Diseases, 1991, 1995, 1997 American
College of Rheumatology
32
Platelet Function Trials Celecoxib vs NSAIDS
(Trials 032 and 065)
Platelet Aggregation at Steady State
Placebo Celecoxib 600 mg BID Naproxen 500 mg
BID Ibuprofen 800 mg TID Diclofenac 75 mg BID
100 80 60 40 20 0
Platelet Aggregation ()





Trial 0321 (N 24) Trial 0652 (N
51) Day 10
Day 8
Plt0.05 vs placebo Plto.5 vs celecoxib 1. Leese
PT, et al. J Clin Pharmacol. 200040124-1322.
Data on file, Searle, a division of Pharmacia
Corporation
33
Pre- and Postoperative Valdecoxib in Patients
Undergoing Hip Arthroplasty Opioid Use
Reduction in Morphine Consumption With Valdecoxib
Cumulative Amount of PCA and Bolus Morphine Used
Postsurgery
41 with 40 mg dose43 with 20 mg dose

Mean Amount of Morphine Consumed (mg)

Placebo MSO4 (n71)
Valdecoxib 40 mg bid MSO4 (n73)
Valdecoxib 20 mg bid MSO4 (n73)
0
4
8
12
16
20
24
28
32
36
40
44
48
Hours
Plt0.001 valdecoxib 20 mg or 40 mg vs
placebo. Camu et al. Am J Ther. 2002943-51.
34
Summary
35
Summary Safety of Celecoxib
  • Upper Gastrointestinal Tract
  • Celecoxib was associated with a significantly
    lower incidence of endoscopic ulcers compared
    with naproxen 500 mg BID
  • A correlation between endoscopic ulceration and
    clinically serious upper GI events has not
    been fully established
  • Platelet Function
  • No significant effect on platelet aggregation and
    bleeding time
  • Liver Function Tests
  • Elevations in liver enzymes similar to placebo

36
Multidimensional Treatment
  • No one specialty comprises the full range of
    knowledge and skills to evaluate and treat
    chronic pain
  • High frequency of limbic sensitization in chronic
    pain requires behavioral health evaluation
    treatment

37
Coanalgesics
  • Potentiate opioids target neuropathic pain
  • Antidepressants / Anxiolytics
  • Anticonvulsants
  • Psychostimulants
  • Serotonin Dopamine Antagonists (SDAs)
  • Psychotherapy

38
Opioid Monotherapy
  • Higher rate of incomplete pain relief
  • (response but not remission)
  • May result in higher doses of opioids
  • Complications shortfalls of opioid monotherapy,
    especially in chronic neuropathic pain states,
    may lead to invalid conclusions about the
    effectiveness and safety of opioids

39
Leading Causes of Disease Burden for Women in the
US in 1996
Also includes other degenerative and hereditary
CNS disorders Michaud CM., et al. JAMA.
2001285535-539
40
Role of Serotonin in the CNS
Serotonin modulates various brain functions
  • Mood
  • Cognition
  • Sensory perception
  • Temperature regulation
  • Nociception
  • (i.e., migraine headache)
  • Sexual behavior
  • Sleep
  • Appetite

41
Chronic Illness Diabetes and Devastating
Depression
Norepinephrine
Serotonin
Anxiety Irritability
Energy interest
Impulsivity
Mood, emotion, cognitive function
Sex Appetite Aggression
Motivation
Drive
Dopamine
42
The Evolution of Antidepressants
1960s
1970s
1980s
1990s
1950s
Imipramine Clomipramine Maprotiline
Fluoxetine Nefazodone (1957)
Nortriptyline Amoxapine Sertraline
Mirtazapine Amitriptyline
Paroxetine Venalfaxine Desipramine
Fluvoxamine ____________
Citalopram Phenelzine
Isocarboxazid Tranylcypromine
43
Figure 1 A Schematic of the NMDAR-Associated
Protein Complex
44
Model for Chronic Activation of Stress Responses
in MDD

  • STRESSOR

CRFcorticotropin-releasing factor
ACTHadrenocorticotropin. Adapted from
Arborelius L, et al. J Endocrinol. 19991601-12.
45
Consequences of Chronic Stress Activation
  • STRESS

Increased survival and growth
Glucocorticoids
Atrophy/death of neurons
BDNF
BDNF
Glucocorticoids
Normal survival and growth
5-HT and NE
Antidepressants
Duman RS, et al. Biol Psychiatry. 200048732-739.
46
Stressful Life Events as a Trigger for
Depression Progressively Declines

  • Kindling Phenomenon
  • With increasing
  • depressive episodes
  • Risk of depression rises
  • Association with stressful life events declines

Risk
Odds ratio for at least 1 stressful life event
during month with a depressive episode. Kendler
KS, et al. Am J Psychiatry. 20001571243-1251.
47
HAMD For 52 Weeks
48
VAS SCALE FOR PAIN52 WEEKS
49
Quality of Life Scale
  • START 20.56
  • END/52 WEEKS 80.77
  • MAXIMUM POINTS 120

50
HealthPlus of MichiganPharmacologic Step
Protocol for Major Depression
SSRI1 (Prozac, Paxil, Zoloft, Celexa prozac
is available as generic
DRAFT
Side effects noted Complaint of
or persistent (eg. GI intolerance)
insomnia
Reduce dose if needed (SSRIs are all equally
effective with comparable tolerability
  • Add low dose (50-100
  • trazodone QHS2
  • Consider Ambien /Sonata if
  • failed trazodone

1. Allow 8-12 weeks to see the full therapeutic
effect (insomnia or somatic complaint of pain
can be part of symptomatic for depression) 2. If
NOT responding within 4-6 weeks ? ? SSRI
gradually 3. If NOT responding after 8-12 weeks
with MAXIMUM dose ? considering the following
alternatives
Draft Document
Page 1 of 3
51
HealthPlus of MichiganPharmacologic Step
Protocol for Major Depression
Remeron 1. Preferred in geriatric
patients with poor appetite or insomnia 2.
Well-tolerated with no significant drug
interactions or dosage adjustment needed for
renal dysfunction
Effexor or Effexor XR 1. Evidence has shown to
be effective in moderate to severe type
depression 2. May be associated with increased
blood pressure (dose-dependent) 3. Effexor XR
provides slower rate of absorption and
comparable drug exposure and plasma fluctuation
as immediate release

DRAFT
Allow 8-12 weeks for full therapeutic effect.
For newly diagnosed episodes of depression,
instruct your patient to continue to take the
antidepressant for at least 6 months.
Page 2 of 3
52
Recurrence Becomes More Likely With Each Episode
of Depression
First episode
lt50
Second episode
70
Third episode
gt90
0 20 40 60 80 100
of patients expected to experience recurrence
Stahl SM. Essential Psychopharmacology
Neuroscientific Basis and Practical Applications.
2nd ed. Cambridge, UK Cambridge University
Press 2000150.
53
Chronic Pain and Diabetes
  • Complementary Therapies
  • Occupational
  • Relaxation
  • Nutrition
  • Cognitive Restructuring

54
Total Healthcare of Michigan, P.C.
Chronic Illness Diabetes and Devastating
Depression
  • 2900 Hannah Boulevard, Suite 200East Lansing, MI
    48823
  • Phone (517) 332-0440
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