Transcript Mental Health

Chronic Illness: Diabetes and Devastating Depression
Total Healthcare of Michigan, P.C.
2900 Hannah Boulevard, Suite 200
East Lansing, MI 48823
Phone: (517) 332-0440
Chronic Illness: Diabetes and Devastating Depression
Chronic Illness: Diabetes and Devastating Depression
Anderson at al, Diabetes Care 24: 1069 – 1078, 2001
 39 Studies
 N = 20,218
Chronic Illness: Diabetes and Devastating Depression
Results
Diabetes….
 Diabetics have 2 times the risk for depression than non-diabetics
 Women > Men prevalence
 1:3 women had depression
Impaired….
 Level of functioning
 Quality of life
 Adherence to medical treatment, therefore, impaired glycemic control
Increased…
 Risk of diabetes complications
Chronic Illness: Diabetes and Devastating Depression
Prospective 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 Med:1997
Chronic Illness: Diabetes and Devastating Depression
HMO 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)
Leading Causes of Disease Burden for
Women in the US in 1996
Percent of all causes
0
1
2
3
4
5
6
7
Ischemic heart disease
Unipolar MDD
Cerebrovascular disease
Lung, trachea, bronchus cancer
Osteoarthritis
Breast cancer
COPD
Dementia*
Diabetes
Road traffic collisions
*Also includes other degenerative and hereditary CNS disorders
Michaud CM., et al. JAMA. 2001;285:535-539
8
Common Presenting Somatic Complaints in
Patients with Depression
• Tired all the time, “blahs”
• Headache
• Sexual dysfunction or loss
of sexual interest
• “Stressed out”
• Malaise
• Vague abdominal or joint
pains
• GI complaints (i.e.,
constipation, diarrhea)
• Disturbed sleep
DSM-IV-TR Washington DC: American Psychiatric Association: 2000.
Mulsant, BH, Ganguli M. J Clin Psychiatry. 1999: 60(suppl 20):9-15.
Common Presenting Psychological Symptoms in
Patients with Depression
• Hopelessness
• Anhedonia
• Low self-esteem
• Anxiety
• Impaired memory
• Preoccupation with negative
thoughts
• Difficulty
DSM-IV-TR Washington DC: American Psychiatric Association: 2000.
Mulsant, BH, Ganguli M. J Clin Psychiatry. 1999: 60(suppl 20):9-15.
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
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
Economics of Depression: Dimensions
Quality of
Life
Workplace
Impact
Burden of Illness
DEPRESSION
Cost of Drug
Therapy
Cost of
Therapy
Failure
Comparative
Data
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
Depression May Worsen Outcomes of Many
General Medical Conditions
Patient Population
Increased Morbidity
Increased Mortality
Post-MI1,2


CHF3,4



Nursing home patients5
Post-stroke6

Depression also may worsen outcomes of cancer, diabetes, AIDS,
and other disorders7
1. Frasure-Smith N, et al. JAMA. 1993;270:1819-1825.
5. Rovner BW, et al. JAMA. 1991;265:993-996.
2. Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221-227. 6. Pohjasvaara T, et al. Eur J Neurol. 2001;8:315-319.
3. Jiang W, et al. Arch Intern Med. 2001;161:1849-1856.
7. Petitto JM, Evans DL. Depress Anxiety. 1998;8(suppl 1):80-84.
4. Vaccarino V, et al. J Am Coll Cardiol. 2001;38:199-205.
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
JACHO 2001
Revised 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.
Two Thalamic Pain Outflows
Sensory Cortex
Limbic System
 Location of pain
Hedonic aspect of pain
 Affective context
Poorly localized
Causes agony & suffering
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
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
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
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
Central Sensitization
Repeated negative inputs
Kindling
Neuroplasticity
Remodeling
Axonal sprouting
Sensitization
10
Hyperalgesia
Injury
Pain Intensity
8
Normal
Pain
Response
6
Hyperalgesia – heightened sense of
pain to noxious stimuli
4
Allodynia – pain resulting from
normally painless stimuli
Allodynia
2
0
Stimulus Intensity
Gottschalk, Smith. Am Fam Physician. 2001;63:1979-1984.
23
Risk Factors for Depression
Loss of a
parent before
age 10 y
Loss support
system of
social
Erectile
dysfunction†
Infertility
Childhood hx
physical or
sexual abuse*
Low levels of
testosterone †
Risk Factors
Personal hx of
mood disorders
in early reproductive
years *
Persistent
psychosocial
stressors
Social or
economic
change †
Family hx
mood disorders
* 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. 1995;56(suppl2):30-37
ACOG. Int J Gynecol Obstet. 1993;43:203-211
Seidman SN, Walsh BT. Am J Geriatr Psychiatry. 1999;7:18-33
Morgan H. Aust Fam Physician. 2001;30:206-211
Theoretical Contributions of
Nature and Nurture to Pathology
Genetic factors
Vulnerability and
resistance genes
Developmental
trajectory
Phenotypic
plasticity
Enriched environment
Social support
Psychiatric
intervention
Trauma
Anxiety disorder
HPA axis dysfunction
Vulnerability
PTSD-like syndrome
Substance Abuse
Long-term
(mal)-adaptation
Adapted from: Plotsky PM, et al. Psychitr Clin North Am. 1998;21:293-307.
Psycho-immune
disease
Depression-like
syndrome
Gender-Specific Differences
in Depression
Parameters
Differences in Women vs Men
Seasonal effect on mood
Greater1
Association with stressful
life events
More frequent2
Atypical symptoms of depression
More common2
(i.e., hypersomnia, hyperphagia)
Suicidal behavior
 Suicide attempt
 Completed suicide
More frequent3
Less frequent3
1. Leibenluft E, et al. Depression. 1995;3:13-19 2. Pajer K. J Clin Psychiatry. 1995;56(suppl2):30-37
3. Hirschfeld RM, Russel, JM. N Engl J Med. 1997;337:910-915
Mortality From NSAID – Induced GI Complications*
Versus Other Diseases in United States
Number of Deaths
25,000
20,000
20,197
16,685
16,500†
15,000
10,503
10,000
5,338
5,000
4,441
1,437
0
Leukemia1 HIV
NSAIDs Multiple Asthma1 Cervical Hodgkin’s
GI2
Myleoma1
Cancer Disease
Cause of Death
Data from 1997
† Estimated
1. National Center for Health Statistics, 1998;
2. Singh G, et al. J Rheumatol. 1999;26 (Suppl 56):18-24
COX-2 and Peripheral Mechanisms of Pain
Tissue Injury
+
+
+++
COX-2
+ ++
++
EP
+
+++++++
receptor ++ PKA
++
++
PKCe
+
PGE2
+
P
+
+
++
+
+
+ + SNS/PN3
+ +
++
++
TTX-resistant
++
sodium
+
+
channel
+
+
+
Resting
Membrane
Potential
Increases
Samad et al. Nature. 2001;410:471-475; Woolf, Salter. Science. 2000;288:1765-1769;
Byers, Bonica. In: Bonica’s Management of Pain. 2001:27-72.
Neuron
Threshold
Firing
Decreases
Pathophysiology of COX-1, COX-2, and COX-3
Glucocorticoids
(block mRNA expression)
Arachidonic Acid
(–)
Acetaminophen
COXIBs
COX-1
(–)
Normal Constituent
Inducible
(–)
(–
)
(–)
COX-3
Normal Constituent
Normal Constituent
COX-2
(–)
(–)
NSAIDs
HOUSEKEEPING
 Stomach
 Intestine
 Kidney
 Platelets
INFLAMMATORY SITE
 Macrophages
 Synoviocytes
 Endothelial cells
NORMAL CONSTITUENT
 CNS
 Kidney
 Female U/G tract
NORMAL CONSTITUENT
 CNS
Pain - Fever
 Heart
 Aorta
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 longterm, 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
APS=American Pain Society; ACR=American College of Rheumatology; AGS=American Geriatric Society.
Adapted from American Pain Society, 2002; ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-1915; Adapted from
American Geriatric Society, 2002.
Malalignment
From the Clinical Slide Collection on the Rheumatic Diseases, 1991, 1995, 1997
American College of Rheumatology
Platelet Function Trials: Celecoxib vs
NSAIDS (Trials 032 and 065)
Platelet Aggregation at Steady State
Placebo
Celecoxib 600 mg BID
Platelet Aggregation (%)
100
Naproxen 500 mg BID
Ibuprofen 800 mg TID
80
Diclofenac 75 mg BID
60
40
20
*
*
†
†
*
0
Trial 0321 (N = 24)
Day 10
Trial 0652 (N = 51)
Day 8
*P<0.05 vs placebo; † P<o.5 vs celecoxib
1. Leese PT, et al. J Clin Pharmacol. 2000;40:124-132;
2. Data on file, Searle, a division of Pharmacia Corporation
Mean Amount of Morphine
Consumed (mg)
Pre- and Postoperative Valdecoxib in Patients
Undergoing Hip Arthroplasty: Opioid Use
Reduction in
Morphine
Consumption With
Valdecoxib
Cumulative Amount of PCA and
50 Bolus Morphine Used Postsurgery
40
*
30
*
*
20
*
41% with 40 mg dose
43% with 20 mg dose
Placebo + MSO4
(n=71)
Valdecoxib 40 mg bid
+ MSO4 (n=73)
10
0
0 4 8 12 16 20 24 28 32 36 40 44 48
Hours
*P<0.001 valdecoxib 20 mg or 40 mg vs placebo.
Camu et al. Am J Ther. 2002;9:43-51.
Valdecoxib 20 mg bid
+ MSO4 (n=73)
Summary
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
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
Coanalgesics
Potentiate opioids & target neuropathic pain





Antidepressants / Anxiolytics
Anticonvulsants
Psychostimulants
Serotonin Dopamine Antagonists (SDAs)
Psychotherapy
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
Leading Causes of Disease Burden
for Women in the US in 1996
Percent of all causes
0
1
2
3
4
5
6
7
8
Ischemic heart disease
Unipolar MDD
Cerebrovascular disease
Lung, trachea, bronchus cancer
Osteoarthritis
Breast cancer
COPD
Dementia*
Diabetes
Road traffic collisions
*Also includes other degenerative and hereditary CNS disorders
Michaud CM., et al. JAMA. 2001;285:535-539
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
Chronic Illness: Diabetes and Devastating
Depression
Norepinephrine
Serotonin
Energy
interest
Anxiety
Irritability
Mood, emotion,
cognitive function
Motivation
Drive
Dopamine
Impulsivity
Sex
Appetite
Aggression
The Evolution of Antidepressants
1950s
Imipramine
(1957)
1960s
1970s
Clomipramine Maprotiline
Nortriptyline Amoxapine
Amitriptyline
Desipramine
____________
Phenelzine
Isocarboxazid
Tranylcypromine
1980s
1990s
Fluoxetine Nefazodone
Sertraline
Mirtazapine
Paroxetine Venalfaxine
Fluvoxamine
Citalopram
Figure 1: A Schematic of the NMDARAssociated Protein Complex
Model for Chronic Activation of Stress
Responses in MDD
Despair
Reproduction
Slow wave sleep
STRESSOR
Behavioral
responses
Eating Immune
function
Electrophysiologic responses
Hippocampus
Anterior
pituitary
CRF
Metabolic responses
Gluconeogenesis
Lipolysis
Proteolysis
Insulin resistance
HPA AXIS
HYPERACTIVITY
Blood
pressure
Heart rate
Blood sugar
Inflammation
Glucocorticoids
Epinephrine
Norepinephrine
GI blood
flow
Autonomic responses
CRF=corticotropin-releasing factor; ACTH=adrenocorticotropin.
Adapted from: Arborelius L, et al. J Endocrinol. 1999;160:1-12.
Kindling
Pyramidal cell
firing rate
Locus ceruleus
firing rate
Locus
ceruleus
Consequences of Chronic Stress Activation
STRESS
Glucocorticoids
Increased survival
and growth
Atrophy/death
of neurons
BDNF
BDNF
Normal survival
and growth
Glucocorticoids
5-HT and NE
Antidepressants
Duman RS, et al. Biol Psychiatry. 2000;48:732-739.
Stressful Life Events as a “Trigger” for
Depression Progressively Declines
10
“Kindling” Phenomenon
Risk (%) of depression onset
per month
Risk
8
With increasing
depressive episodes:
6
• Risk of depression rises
4
• Association with stressful
life events declines
2
Likelihood of recent life stress*
0
0
2
4
6
8
10
Number of previous depressive episodes
*Odds ratio for at least 1 stressful life event during month with a depressive episode.
Kendler KS, et al. Am J Psychiatry. 2000;157:1243-1251.
DEPRESSION LEVEL
HAMD For 52 Weeks
18
16
14
12
10
17.317
8
6
4
8.902
2
0
PRE 1ST WEEK
POST 52ND WEEK
VAS SCALE FOR PAIN:52 WEEKS
PAIN LEVEL
10
8
6
8.486
4
3.667
2
0
PRE 1ST WEEK
POST 52ND WEEK
Quality of Life Scale
 START: 20.56
 END/52 WEEKS: 80.77
 MAXIMUM POINTS: 120
HealthPlus of Michigan
Pharmacologic Step Protocol for Major Depression
SSRI1
(Prozac*®, Paxil®, Zoloft®, Celexa®
*prozac is available as generic
Side effects noted
(eg. GI intolerance)
Reduce dose if needed (SSRIs
are all equally effective with
comparable tolerability
Complaint of or persistent
insomnia
1. Add low dose (50-100
trazodone QHS2
2. 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:
Page 1 of 3
Draft Document
HealthPlus of Michigan
Pharmacologic 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
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
Recurrence Becomes More Likely With
Each Episode of Depression
First
episode
<50%
Second
episode
≈70%
Third +
episode
>90%
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; 2000:150.
Chronic Pain and Diabetes
Complementary Therapies
Occupational
Relaxation
Nutrition
Cognitive Restructuring
Chronic Illness: Diabetes and Devastating Depression
Total Healthcare of Michigan, P.C.
2900 Hannah Boulevard, Suite 200
East Lansing, MI 48823
Phone: (517) 332-0440