Psychosocial Impact of Multiple Sclerosis:

Patient’s Perspective (Mohr et al. 1999)

Demoralization & Depression in
Multiple Sclerosis & Transverse Myelitis
Adam Kaplin, MD, PhD
Johns Hopkins University School of Medicine
Departments of Psychiatry & Neurology
JHTMC & JHMSC
• Phone interviews used to explore psychosocial
functioning, defined as intrapersonal or interpersonal
processes excluding physical symptoms.
• Demographics: 100% RR MS, Northern CA, 75% women,
Average 43 y/o, 63% married, 55% employed.
• Psychosocial impact of MS clustered into 3 factors:
– Deterioration in Relationships: endorsed overall by 20%.
– Demoralization: endorsed overall by 30%.
– Benefit-Finding: endorsed overall by 60%.

Benefit-Finding: (% endorsing)
• Relationships: “If you can’t be normal, be spectacular!!!”
– My friends and family have become more helpful (77), I am
closer to my family (70), I am closer to my significant other
(51), I keep in better touch with my family (44)
• Interpersonal Skills:
– I have learned to be more compassionate (67), to be more
respectful of others (58), express more feelings (55), QuickTime™ and a
communicate better (48), be a better friend (48), TIFF (Uncompressed) decompressor
are needed to see this picture.

• Perspective:
– I appreciate the importance of being independent (83), I
appreciate life more (74), I am more introspective (72),
more conscientious and self-disciplined (60), more
motivated to succeed (59), more spiritual (45), more
independent in many ways (38), less inhibited (33)

Anatomy of Despair:
There is no despair so absolute as that which Demoralization vs Depression
comes with the first moments of our first
great sorrow,
when we have not yet known what it is to
have suffered and be healed,
to have despaired and have recovered hope.
George Eliot (1819-1880)

1
 Demoralization (Frank & Frank, 1993) Who Cares About Caregivers (CG)?
• Demoralization = state of helplessness, hopelessness,
confusion, subjective incompetence, isolation and • Poorly studied but critically important aspect of all chronic illnesses.
diminished self-esteem.
• There are both positive and negative aspects to being a CG.
– Results from failure to adapt when environmental stress
• Well-being of CG is crucial to well-being of care-recipient (CR).
overwhelms an individual’s coping capacity.
• CG report increased frequency of loss, loneliness and isolation.
– An individual’s coping capacity is influenced by constitutional
variables and resources. • Decreased wellness of CG because of neglect of their own health.
• Subjective thoughts, feelings, beliefs of demoralized • MS CR variables associated with increased CG burden:
individuals: – Unstable course, increased physical disability, depression, and pain.
– Failed to meet expectations: their own and/or others’ expectations. • CG & CR are in it together:
– Overmastered: – In sickness and in health.
• Feeling of being unable to cope with some pressing problem. – My body/My spouse’s body/My family
• Simultaneous feelings of being powerless to change situation or
extricate themselves from predicament.
– Isolated:
• Feeling of being unique and therefore not understood.

MDD
Are you getting enough oxygen?

QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

Man in Deep Depression

What is Depression???
If You’ve Never Had It (Tx), Forget What You Know
• Mood thermostat in brain gets stuck
– Mostly fixed, unresponsive low mood.
– Accompanied by physical Sx: e.g. concentration, sleep, energy,
appetite.
– Brain alterations (e.g. REM, hippocampus).
• Drugs exploit the fact that the brain regulates our mood.
– Cocaine
• ALS: Tuesday’s With Morrie
• Under-appreciation of the role of biology…
– It’s NOT all in your mind!
– MS/TM Sx Onset -> Must convince physician.
– Depression Sx Onset -> Must convince yourself.

2
 Forget what you “know” about depression: Medical Causes of Depression:
Common myths in and out of Medicine
• Neurologic disorders: CVA (25-50%), subdural hematoma, epilepsy (45-
55%), brain tumors (30%), Parkinson's disease (30-50%), Huntington's
• Depression is a state of mind, weakness or character flaw disease(40%), syphilis, Alzheimer's disease (15-50%)
– Genetics • Autoimmune disorders: DM (30%), SLE (25-44%), RA (30-50%), Multiple
Sclerosis (37-62%), Transverse Myelitis
– REM latency
• Drug induced: reserpine (15%), interferon-alpha (10-57%), β-blockers,
– DST corticosteroids, estrogens, benzodiazepines, barbiturates, ranitidine, Ca2+-
– Medical causes of depression (MS, TM, NMO, etc) channel blockers
• Substance induced (25%): EtOH, sedative-hypnotic, cocaine &
psychostimulant withdrawal
• Metabolic: hyper/hypothyroidism, Cushing's syndrome, hypercalcemia,
hyponatremia, diabetes mellitus
• Nutritional: vitamin B12 deficiency
• Infections: HIV, HCV, mononucleosis, influenza
• Cancer (20-45%): especially pancreatic CA (40-50%)

Forget what you “know” about depression:

Common myths in and out of Medicine
• Depression is not a serious concern
– “Far more Americans die from suicide than from homicide.” Satcher 1999.
• 3rd leading cause of death general population ages 1-24.
• 4th leading cause of death general population ages 25-44.
• 1st leading cause of death in physicians ages 25-44.
– Single best predictor of cardiac mortality in 12 months following MI.
– Second leading chronic cause of disability in daily functioning in US.
– A leading cause of disability world-wide (WHO-DALY).

(DHHS, 2002)

“I can’t understand a word you’re saying, Roger.

Have you got a gun in your mouth?”

Forget what you “know” about depression:

Common myths in and out of Medicine What Depression is NOT: Normal Sadness
• There are two simple myths that are used (John Lipsey, MD)
inappropriately to dismiss the diagnosis of
• Intermittent, universal experience
depression.
– Patients are not depressed, they are stressed. • Depression with a small "d"--a symptom
• Stress is not protective against depression, • Degree and duration appropriate to stressor
especially medical stress.
• Unaccompanied by other severe or persistent
• DSM does not make allowances for stress.
psychological symptoms.
– OK they’re depressed, but you’d be depressed too
if you had their illness. • Responsive to environment (eg good news)
• Depression is not the inevitable consequence of • Doesn’t unduly disrupt work or social function
stress.
• ALS & Tuesdays with Morrie.
• MS and disability.

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 Major Depression vs Sadness: DSM IV Inventory: SIGEMCAPS
• Major depression is a syndrome. • Sleep ( ⇓ / ⇑ )
• Interest (or pleasure)
• It is not just severe sadness. • Guilt (or worthlessness)
• Sadness is to major depression what cough is to • Energy (fatigue)
pneumonia. • Mood
– Cough can be an indicator of pneumonia. • Concentration
– Not every cough is the result of pneumonia. • Appetite ( ⇓ / ⇑ or weight loss or gain)
– Sometimes pneumonia presents without a cough. • Psychomotor retardation (or agitation)
– Consider the company the cough keeps. • Suicidal ideation (or thoughts of death)
• Productive sputum, tachypnea, fever, consolidation • ≥5/9 Sx for ≥2 weeks

Jean-Martin Charcot(1825–1893):
Disseminated Sclerosis
Burden of Depression in MS Patients
• Grief, vexation, and adverse changes in (Patten & Metz, Psychother Psychosom, 1997, 66:286-92)
social circumstance were related to the
onset of MS. • Lifetime Prevalence:
• 1868, The Lectures on the Diseases of the – 37-62% MS
Nervous System to medical students at La
– 17% General Population (NCS)
Salpetriere in Paris
• Current Prevalence:
• Charcot, Lecture VII, 1868.
– Mlle. V. was a 31-year-old woman with 8 yr – 14-27% MS
history of DS. – 5% General Population (NCS)
– Experienced periods of serious depression
accompanied by paranoia that caused her to
suspect Charcot of trying to poison her.
– As a result, she ceased eating and had to be
fed by a stomach pump to keep her alive.

4
 Depression and MS Impact of Depression in MS
• Depression is common in patients with MS and
is associated with considerable morbidity and • Quality of Life
mortality. • Function
• The available evidence suggests depression in –Primary relationship
MS is caused by the effects of inflammatory
insults to the brain. –Work
– No correlation with physical disability. –Treatment Adherence
– No genetic loading. • Cognition
– Periods of immune activation correlate with • Fatigue
increased depression and suicides.
• Longevity

Causes of Death in Patients with MS

MS Depression and Suicide: Epidemiology
Pericarditis
1% • 30% lifetime incidence of suicial intent in MS.
Asphyxiation
1%
Renal Failure
• 6-12% of patient with MS attempt suicide.
3%
Respiratory Failure • Suicide in MS occurs at 7.5 x general population.
3%
Pulmonary Embolism
4%
Pneumonia
23%
• Suicide was 3rd leading cause (15%) of death in 3000
Pneumonia
Miscellaneous
5%
Cancer outpatients in Canadian MS clinics 1972-1988.
Suicide
Pulmonary Edema Heart Attack – MS patients dying from suicide were younger and less
6% Stroke
Aspiration Pneumonia disabled than patient dying from Pneumonia (23%) and
Aspiration Pneumonia
6%
Pulmonary Edema
Miscellaneous
Cancer (16%). (Sadovnick, et al, 1991, Neurology)
Pulmonary Embolism
Stroke Cancer
16%
Respiratory Failure • Forensic study of 50 MS autopsies in MD between
6% Renal Failure
Asphyxiation 1982-2004 found suicide (8%) second to CVD (18%) as
Heart Attack
11%
Pericarditis
causes of unexpected deaths. (Riudavets, et al, 2005,
Suicide
15% AJFM).

Introduction to Transverse Myelitis (TM): Depression Scores in TM, MS and the General Population
TM Defined
90
84
• Transverse: 80

– Lying or being across, or in a 70

Percent Population

crosswise direction; 62
60
– often opposed to longitudinal. T
49 51
• Myelitis: 50 Euthymic
Mild-Mod
0 - 59
60-69
– An inflammation or infection of 40 39
35
Severe 70-81
All Depression 60-81
the spinal cord. 30
31

20
14 16 16
10 8
2
0
Gen Pop MS TM

5
 Quartile distribution of test scores in ATM and MS patients Correlation Between Neurological
Disability and Depression Scores
100%
90%
80%
70%
Sexual Fxn
MS
60%
50% Series4
Series3
Bladder Disab
40% Series2

30%
Series1
Motor Disab
20%
10%
Sensory Disab
0%
MMSE Trails Trails Rey- FAS
A B recall
Sensory Disab
100% r=0.307, p=0.004*
90%
70

Depression
80% Motor Disab
70% r=0.020, p=0.901
60% 60
TM 50%
Series4
Bladder Disab
40% Series3
Series2
Series1 50 r=0.060, p=0.731
30%
20% Sexual Fxn
10% 40 r=0.026, p=0.875
0%
MMSE Trails Trails Rey- FAS
1 2 3 4 5
A B recall Disability

Suicide Rate: Depression vs MS vs TM SIGEMCAPS --> MS & TM

• Sleep ( ⇓ / ⇑ ) --> Insomnia
1000
1000 • Interest (or pleasure) --> Relationship Strain
900
• Guilt (or worthlessness) --> Barrier to rehab & Tx
800
• Energy (fatigue) --> MS Fatigue
700
600 General Populati
• Mood --> Sadness
500 Depression • Concentration --> MS memory loss
400 MS • Appetite --> Weight loss & decreased
TM Energy.
300
200 • Psychomotor retardation --> MS memory loss, decreased
Ambulation.
100 168
12 83 • Suicidal ideation --> Hopelessness, Death.
0
Annual Suicide Rate (per 100,000) • Magnification of suffering --> Chronic Pain

Potential Effects of Treating Depression on MS:
• Chronic stress has been linked to increased risk for MS
exacerbations as well as accrual of disability. (Mohr, et al)
• A prospective, longitudinal investigation involving serial
imaging using MRI with gadolinium demonstrated that
stressful life events (especially family conflict and work
related stress) predicted the development of new and active
brain lesions.
• A meta-analysis of studies examining the effects of stress
on MS exacerbation found a significantly elevated risk of
exacerbation associated with stressful life events in 13 of
the 14 investigations.
• The degree that stress increased the risk of MS
exacerbations in this meta-analysis was on average 60%
greater than the degree that IFN-beta treatment has been
shown to decrease the risk of MS exacerbations.
Treatment of Depression in MS is Associated with Decreased
IFN-gamma Production by Autoaggressive T Cells
(Mohr et al, 2001, Arch Neurol, UCSF)
• Patients with depression had biological evidence of worse
MS disease severity.
• Treatment of depression in MS patients (with either
medication or psychotherapy) correlated with
improvement in their autoimmune disease status.
• Suggests that treatment of depression may be an
important component in the management of MS:
– “Treatment of depression may provide a novel disease-
modifying therapeutic strategy as well as a
symptomatic treatment for patients with MS.”
• Stress has been linked to increased risk for MS
exacerbations as well as accrual of disability. (Mohr, et al)

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 Forget what you “know” about depression:
Common myths in and out of Medicine
• 5. Depression is not treatable…
– I can think of no other illness that has the same burden of morbidity
and mortality of MDD that can be put into 100% symptomatic
remission with proper recognition and treatment.
– USAF experience: Suicide Prevention Program 1996-1998.

Causes of death among active duty USAF

personnel, 1990-1994

Unintentional
Injury (48%)
Suicide (23%)

Disease (21%)

Homicide (5%)

Other (3%)

MMWR
“Of course your daddy loves you.
He’s on Prozac--he loves everybody.”

Relationship Between Depression & Autoimmune

CNS Diseases “The deeper sorrow carves into you, the more
• Depression and MS: A Two-Way Street joy you can hold.”
– MS cause depression. Kahlil Gibran
– Depression/Stress worsens MS.
– Treating Depression improves MS. “The one law that does not change is that
– Treating MS improves depression. everything changes, and the hardship I was
• Depression is a lethal consequence of MS if bearing today was only a breath away from the
untreated. pleasures I would have tomorrow, and those
• Depression is common & important, caused by the pleasures would be all the richer because of the
immune system in autoimmune diseases, and memories of this I was enduring.”
treatable. Louis L’Amour (1908-1988)

“I have had to face many challenges in my life. I have had to endure numerous
physical and emotional hardships. But my positive attitude and my sense of hope for
today and the future have never been diminished. My life is good, because I will have it
no other way. My life is beautiful, because I choose to see life this way. We cannot
control all of what happens with our bodies, and we cannot control what goes on in the
Acknowledgements:
world around us. But we do control how we think about and feel about ourselves and
our families and the world we live in. And it is all good; life is very, very good.” • Douglas Kerr & Chitra Krishnan
• CUFSF & TMA & TM/MS Patients/Families
• Ben Greenberg & Peter Calabresi
• JHTMC & JHMSC
• Michele Pucak & Edward Hammond
• David Edwin & Karen Swartz
• Glenn Treisman & Peter Rabins

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 “No pill can help me deal with the
problem of not wanting to take pills; likewise, no
amount of psychotherapy alone can prevent my
manias and depressions. I need both. It is an odd
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

thing, owing life to pills, one’s own quirks and

tenacities, and this unique, strange, and
ultimately profound relationship called
psychotherapy.”
Dr. Kay Redfield Jamison

Association Between IV Steroid Treatment and

Depression: 70% Increase
AD RR of SRE CI

Effexor (5) 4.97 1.09-22.72 90

Paxil (15) 2.65 1.00-7.02 80 85
Zoloft (24) 1.48 0.42-5.24
70
Prozac (120) 0.92 0.39-2.19
60
% Normal 50
Depression 40 50

30
20
10
0
-IV Steroid+IV Steroid
(Nature Med, Feb 2005)

(Wells KB, et al, JAMA, 1989)

Depression is currently the 2nd leading cause of

disability from chronic illnesses.

8
 Immune Activation

Recognition of Self as Foreign/ Over-activation

Central Nervous System Inflammation

Stop

IL-6
Stress

Cortisol
Hippocampal Neurogenesis Decreased Division

Antidepressant
Growth of New Neurons Hippocampal Shrinkage
BDNF
Mood Regulation Depression
“Of course your daddy loves you.
Learning & Memory Cognitive Impairment He’s on Prozac--he loves everybody.”

“I'm still able to do the things I enjoyed before I got TM.

6
I can still play around with computers, listen to music and
watch movies. Now I have more time to spend doing it!… y = 30.607x + 0.8135
2
R = 0.9775
When life isn’t the way you like it, like it the way it is, one day at a time.”
5
Relative Risk of Suicide Related Events

RR SRE
3
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Linear (RR SRE)

0
0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16
Clearance

JHTMC Patient Demographics Medical Causes of Depression:

• Neurologic disorders: CVA (25%), subdural hematoma, epilepsy (45-55%),
brain tumors (30%), multiple sclerosis (37-62%), Parkinson's disease (40-50%),
MS TM p value Huntington's disease(40%), syphilis, Alzheimer's disease (15-50%)
• Autoimmune disorders: multiple sclerosis (37-62%), rheumatoid arthritis (30-
50%), DM (30%), SLE (25-44%).
Patients 26 74 • Drug induced: reserpine (15%), interferon-alpha (10-57%), β-blockers,
corticosteroids, estrogens, benzodiazepines, barbiturates, ranitidine, Ca2+-
channel blockers
Age 45 46 0.616 • Substance induced (25%): EtOH, sedative-hypnotic, cocaine & psychostimulant
withdrawal
(average)
• Metabolic: hyper/hypothyroidism, Cushing's syndrome, hypercalcemia,
Sex 84 60 0.02 hyponatremia, diabetes mellitus

(% women) • Nutritional: vitamin B12 deficiency

• Infections: HIV, HCV (25%), mononucleosis, influenza
Motor 1.7+/-1.4 1.8+/-1.3 0.73 • Cancer (20-45%): especially pancreatic CA (40-50%)
Disability
(+/- SD)

9
 Forget what you “know” about depression:
Five common myths in and out of Medicine
• 4. There are two simple myths that are used inappropriately to
dismiss the diagnosis of depression.
– Patients are not depressed, they are stressed.
• Stress is not protective against depression, especially medical stress.
• DSM does not make allowances for stress.
– OK they’re depressed, but you’d be depressed too if you had their
illness.
• Depression is not the inevitable consequence of stress.
• ALS & Tuesdays with Morrie.
• MS and disability.

(Science, 2003, 386-390)

Impact of Depression on MS Patients Introduction to Transverse Myelitis (TM):

TM Defined
(Patten & Metz, Psychother Psychosom, 1997, 66:286-92)

• Impedes rehabilitation and adversely affects • Transverse:

QOL and function. – Lying or being across, or in a
crosswise direction;
• Association between cognitive dysfunction,
– often opposed to longitudinal.
fatigue and depression.
• Myelitis:
• Rate of suicide is 7.5-14 times greater in MS – An inflammation or infection of
patients than the in the general population. the spinal cord.

Conclusions About Depression in TM

• Depressive symptoms occur at a markedly high rate
in TM that is comparable to that of MS.
• Depressive symptoms do not correlate with the
degree of motor or autonomic disability, spinal
level, or other tested biological markers of disease.
• There was a correlation between sensory disability
(“prickling” & “tingling”) and depressive symptoms
that accounted for 9% of the variance.
• Treatment with IV Steroids correlates with an
increased rate of depressive symptoms.
• Increased depression correlates with high rates of
suicide in TM.

10
 Effects of Treatment of Depression on MS Treating MS Depression
• Treatment related-reductions in depression in MS patients are
associated with reductions in T-cell production of IFN-gamma • MS depression is usually unremitting and tends to get worse
(IFN-y) (Mohr). without treatment.
• IFN-y is the main proinflammatory cytokine produced by activated • Only DBPC Trial was Desipramine x 5 wks.
T cells that has been shown to precede and cause exacerbations and – Desipramine improved depression more than placebo.
new brain lesions in MS patients. – 50% of patients on deisipramine had to limit dose because of side-
effects.
• T cells isolated from depressed MS patients were found to be primed
to produce twice the levels of IFN-y than T cells from non-depressed • Open label trials:
controls. – Fluvoxamine: 80% response rate.
• Treatment with sertraline or psychotherapy reduced depression that – Setraline: 90% response rate.
was paralleled by declines in T-cell IFN-y production, which • Psychotherapy:
returned to control levels. – CBT > Insight Oriented
• Treating depression might prove to be an important disease • Exercise.
modifying component in MS treatment.

Studying Depression: Depression Has Been Known Since The Time Of The Greeks:
(HS Akiskal, Comp Text Psych, 6th ed & Galen, Diseases of the Black Bile, 165 CE)

In Search of Homogeneity
• Hippocrates (460-357 BC) first described "melancholia"
• SIGEMCAPS • MSGEC ("black bile") as a state of "aversion to food, despondency,
• MSIGE • MSGECA sleeplessness, irritability, [and] restlessness."
• MSGECAP
• MSIGEC • He believed the illness arose from the substrate of the somber
• MSGECAPS
• MSIGECA melancholic temperament, which, under the influence of the
• MSIEC
• MSIGECAP
• MSIECA
planet Saturn, made the spleen secrete black bile, which
• MIGEC
• MSIECAP
ultimately darkened the mood through its influence on the brain.
• MIGECA
• MSIECAPS… • Furthermore, Hippocrates “declared that the bile inflicts damage
• MIGECAP
• MIGECAPS
to the brain as an instrument,” thereby impairing its “function as
• SIGEM ICAPS
an organ” and affecting the intellect.

“Many fail to realize that far more

Americans die from suicide than
from homicide.”
Surgeon General Satcher, 1999

11
 DSM IV Inventory: SIGEMCAPS
• Sleep ( ⇓ / ⇑ )
• Interest (or pleasure)
• Guilt (or worthlessness)
• Energy (fatigue)
• Mood
• Concentration
• Appetite ( ⇓ / ⇑ or weight loss or gain)
• Psychomotor retardation (or agitation)
• Suicidal ideation (or thoughts of death)
• ≥5/9 Sx for ≥2 weeks
Treat Demoralization with Remoralization
• Problem-focused coping skills to instill sense of mastery.
– e.g.: rest periods to combat fatigue, shop non-peak hrs, etc.
– Cumulative small victories can re-instill confidence.
– Combats helplessness, diminished self-esteem, frustration.
• Individual and group support and education.
– e.g.: this conference, friends, counselors, care-providers.
– Combats hopelessness and isolation.
• Cognitive reframing
– e.g.: “reality checks”, untreatable memory disorder becomes
organizational problem.
– Combats subjective sense of incompetence & confusion.
• Occasional reminder that its OK to be merely human.
– e.g.: nonjudgmental setting where feelings can be expressed
Depression & Quality of Life
• Multiple studies have shown that depression is the
primary determining factor in patient’s self
reported quality of life, with greater impact than
other variables investigated, including physical
disability, fatigue, cognitive impairment.
• Epidemiology of Major Depressive Disorder
(MDD):
– Current (30d) prevalence: 5%
– Lifetime prevalence: 17% (M 12%, F 21%)
– Peak age of onset 20-40 years old.
Who Cares for Caregivers? (Peter Rabins: 36 hr Day)
• Care-Provider’s who care about patients care about CG.
• CG & CR must remember they are in this together.
– Coping strategies must therefore be complementary.
– There’s not just one way to adapt to life under altered circumstances.
• Problem-focused coping skills.
– What can and can’t be changed.
– Continually increased distress by either CR or CG means something new
must be tried. Avoid entrenchment in a failed solution.
• Information is crucial.
– CG must be informed about TM.
• What you don’t know can scare you…a lot!!!
• Education can provide tools to help problem solve.
– Peer education is often invaluable. You’re not the first to need advice.
• As a CG, ask “how am I doing?” (physically, emotionally, etc).
– Taking care of CG’s needs doesn’t conflict with CR needs.
– CG is no good to CR if she/he is burnt out. Know how to get help.
Depression and Function
• Depression is the primary determining factor in the
quality of primary relationship when rated both
by the patients and their significant others.
• Depression is associated with
– Disruption of social support.
– Increased time lost from work,
– Decreased adherence to neuromedical treatment
regimens for MS.
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 Depression and Cognition
• Some degree of cognitive impairment occurs in 50% of MS
patients:
– Memory recall, information processing speed, executive
function, working memory
• Cognitive deficits also found in moderate-severe MDD.
– Performance in depressed MS patients may be normal for
routine tasks but impaired on tasks involving effortful
attention.
– Depression in MS associated with impairment of complex
speeded attention, planning and working memory.
– Impairment can wax and wane with type of task and mood.
• Conclusions:
– Both MS and depression have overlapping cognitive deficits.
– Combination of two is additive in resulting impairment.
“And please let Alan Greenspan accept the things he
cannot change, give him the courage to change the things
he can, and the wisdom to know the difference”
Depression and Fatigue
• Depression strongly associated with impact of fatigue on lives
of MS patients (vs. occurrence).
• Association of depression with fatigue is type specific (Siegert &
Abernathy, 2005, JNNP):
– Mental fatigue, r=0.54, p<0.0001
– Physical fatigue, r=0.31, p<0.01
• Disabling fatigue = often or almost always interferes with
activities (Chwastiak, et al, 2005, JPR):
– MS subjects with depression 6x more likely to report disabling
fatigue.
– Presence of disabling fatigue had sensitivity & specificity of 70%
for predicting significant levels of depression.
13