Download Recognition & Treatment of Depression

Recognition and
Treatment of Depression:
Reducing Suicide and
Misery in Difficult Times
Charles B. Nemeroff, MD, PhD
Leonard M. Miller Professor and Chairman
Department of Psychiatry and Behavioral Sciences
Director, Center on Aging
University of Miami, Miller School of Medicine
Miami, Florida 33136
CHARLES B. NEMEROFF, M.D., PH.D.
DISCLOSURES
• Research/Grants: National Institutes of Health (NIH), Agency for Healthcare Research
and Quality (AHRQ)
• Speakers Bureau: None
• Consultant: Xhale, Takeda, SK Pharma, Shire, Roche, Lilly
• Stockholder: CeNeRx BioPharma, Inc., PharmaNeuroBoost, Revaax Pharma, Xhale
• Other Financial Interest: CeNeRx BioPharma, PharmaNeuroBoost
• Patents: Method and devices for transdermal delivery of lithium (US 6,375,990B1),
Method of assessing antidepressant drug therapy via transport inhibition of monoamine
neurotransmitters by ex vivo assay (US 7,148,027B2)
• Scientific Advisory Board: American Foundation for Suicide Prevention (AFSP),
CeNeRx BioPharma, National Alliance for Research on Schizophrenia and Depression
(NARSAD), PharmaNeuroBoost, Anxiety Disorders Association of America (ADAA),
Skyland Trail
• Board of Directors: AFSP, Gratitude America
3
Canst thou not minister to a mind diseased?
Pluck from the memory a rooted sorrow,
Raze out the written troubles of the brain,
And with some sweet oblivious antidote
Cleanse the stuffed bosom of that perilous
Stuff which weighs upon the heart?
MACBETH
4
All his life he suffered spells of
depression, sinking into the brooding
depths of melancholia, an emotional
state which, though little understood,
resembles the passing sadness of the
normal man as a malignancy
resembles a canker sore.
William Manchester,
The Last Lion, Winston Spencer Churchill, Vol. I: Visions of Glory
(New York: Little, Brown & Company, 1989, p. 23)
5
Major Depressive Episode:
DSM-IV Diagnostic Criteria
•
•
Characterized by clinically significant distress and/or
impairment in social, occupational, or other important
areas of functioning
Symptoms must persist for most of day, nearly every
day, for  2 consecutive weeks
DSM-IV. 1994.
6
DSM-IV Diagnostic Criteria
for Major Depression
•
•
 5 symptoms including depressed mood and/or anhedonia
– Other symptoms may include:
– Significant weight change
– Psychomotor agitation/retardation
– Pervasive loss of energy/fatigue
– Feelings of worthlessness/excessive or inappropriate guilt
– Difficulty concentrating
– Sleep disturbance
– Recurrent thoughts of death/suicide
Symptoms present for  2 weeks
DSM-IV. 1994.
7
Prevalence of Depression in United States
Katon W. Schulberg H. Gen Hosp Psychiatry. 1992; 14: 237-247
8
Global Burden of Disease and Injury Series
THE GLOBAL BURDEN
OF DISEASE
A comprehensive assessment of mortality and disability from
diseases, injuries, and risk factors in 1990 and projected to 2020
EDITED BY
CHRISTOPHER J. L. MURRAY
Harvard University
Boston, MA, USA
ALAN D. LOPEZ
World Health Organization
Geneva, Switzerland
Published by The Harvard School of Public Health on behalf of The
World Health Organization and The World Bank
Distributed by Harvard University Press
5/24/2017
9
Depression—A Major Cause of Disability Worldwide
DALYs—2000 and 2020
Rank
20001
1 Lower respiratory infections
2 Perinatal conditions
3 HIV/AIDS
4 Unipolar major depression
5 Diarrheal diseases
2020 (Estimated)2
Ischemic heart disease
Unipolar major depression
Road traffic accidents
Cerebrovascular disease
Chronic obstructive pulmonary disease
1.World Health Report 2001. Mental Health: New Understanding, New Hope. Geneva, World Health Organization, 2001.
2. Murray CJL, Lopez AD, eds. The Global Burden of Disease. Boston: Harvard University Press; 1996.
DALYs=disability-adjusted life-years.
10
The leading causes of disease
burden for women, aged 15-44, 1990
Percent of all causes in developed or developing regions
CAUSES
Unipolar major depression
Schizophrenia
Road traffic accidents
Bipolar disorder
Obsessive-compulsive disorder
Alcohol use
Osteoarthritis
Chlamydia
Self-inflicted injuries
Rheumatoid arthritis
Tuberculosis
Iron-deficiency anaemia
Obstructed labour
Maternal sepsis
War
Abortion
11
11
Postpartum Depression (PPD)
• 10% to 15% in adults*
• 26% of adolescents†
*Stowe and Nemeroff. Am J Obstet Gynecol. 1995; 173: 639-645.
†Troutman and Cutrona. J Abnorm Psychol. 1990; 99: 69.
13
Depressive Disorders After Miscarriage
• >33% severely depressed*
•  duration of pregnancy =  risk of
depressive disorder*
• Treat depressive disorders if reaction
beyond expected grief and bereavement
*from Janssen et al. Am J Psychiatry. 1996; 153: 226-30.
5/24/2017
14
Depressive Disorders in Children
Prevalence of Depressive Disorders in Children*
•
•
•
Preschool children – 0.8%
School-aged prepubertal children – 2.0%
Adolescents – 4.5%
Key Issues†
•
•
•
Distinguish between depressive disorders and
behavioral disorders
Depressive disorders before age 20 often associated
with recurrent mood disorders in adulthood
30% of adolescents hospitalized with severe major
depressive disorder develop bipolar disorder
*Weller EB, Weller RA. In: Psychiatric Disorders in Children and Adolescents. 1990: 3-20.
†Depression Guideline Panel. Depression in Primary Care: Volume 1. Detection and Diagnosis. 1993: 1-65.
Giles DE, Jarrett RB, Biggs MM, et al. Am J Psychiatry. 1989; 146: 765-767.
Strober M, Carlson G. Arch Gen Psychiatry. 1982; 39: 549-555.
15
Depressive Disorders in Older Age
• Occur in approximately 15% of
population >65 years old
• May mimic dementia
• Comorbid somatic symptoms
• Not due to “old age”
• Require appropriate treatment
Data from NIH Consensus Development Panel on Depression in Late Life. JAMA. 1992; 288: 1018-24.
16
Depression is Often Under Diagnosed
and Inadequately Treated
• Less than 1/2 of patients with major depression
are explicitly recognized as
being depressed1
• Only about 1/2 of all depressed patients receive
some form of therapy for their illness2
• Only about 1/4 of depressed patients
receive an adequate dose and duration
of antidepressant treatment3
1. AHCPR. Rockville, Md: US Dept of Health and Human Services; 1993. Publication 93-0550.
2. Lepine JP, et al. Int Clin Psychopharmacol. 1997;12(1):19-29.
3. Katon W, et al. Med Care. 1992;30(1):67-76.
17
Mania
Depression
Total mood variation
The Mood-Disorders Spectrum
Normals
Cyclothymia
Bipolar I
Disorder
Bipolar II
Disorder
Dysthymia
Unipolar
Depression
18
19
FACING THE FACTS…
The suicide rate was 11.8/100,000 in
2008.
It exceeds the rate of homicide
greatly.
Suicide is the 10th leading cause of
death in the United States.
Of the 50 states, Florida is # 15 in
suicide rate in 2007.
20
FACING THE FACTS…
21
FACING THE FACTS…
Suicide is considered to be the
second leading cause of death among
college students. 1100 college
students died by suicide in 2009.
Suicide is the third leading cause of
death for youth, 5-24 years old.
Suicide is the fourth leading cause of
death for adults between the ages of
18 and 65.
22
FACING THE FACTS…
Research shows that during our lifetime:
20% of us will have a suicide within our
immediate family.
60% of us will personally know
someone who dies by suicide.
23
SUICIDE DEATHS AND MAJOR PSYCHIATRIC SYNDROMES
<10% without
Major Psychiatric
Syndromes
>90% with Major
Psychiatric Syndromes
A number of psychological autopsy studies have found that approximately 90% of all completed suicides could be
retrospectively diagnosed with a major mental disorder.
24
SUICIDE IS AN OUTCOME THAT REQUIRES SEVERAL THINGS TO GO
WRONG ALL AT ONCE.
-- There is no one cause of suicide and no single type of suicidal person.
Biological
Factors
Familial
Risk
Predisposing
Factors
Proximal
Factors
Immediate
Triggers
Major Psychiatric
Syndromes
Hopelessness
Public Humiliation
Shame
Serotonergic
Function
Substance
Use/Abuse
Intoxication
AccessTo
Weapons
Neurochemical
Regulators
Personality
Profile
Impulsiveness
Aggressiveness
Severe
Defeat
Demographics
Abuse
Syndromes
Negative
Expectancy
Major
Loss
Severe Medical/
Neurological Illness
Severe
Chronic Pain
Worsening
Prognosis
Pathophysiology
25
TRIGGERING EVENTS
― Loss of social support (friends, family)
― Loss of identity/meaning (job, career, financial, legal
problems)
― Loss of independence/autonomy, or function (major health
problem)
― Acute psychiatric symptoms (psychosis, depression,
panic…)
― Loss of hope/Sense of failure
― Date of a significant past interpersonal loss: Anniversary
reaction
26
27
Comorbidity
Lifetime comorbidity of mood and anxiety disorders
48% of patients with PTSD1
Up to 65% of patients with Panic
Disorder2
Post-Traumatic
Stress Disorder
Social
Anxiety
Disorder
Up to 70% of patients with
Social Anxiety Disorder5
Panic
Disorder
DEPRESSION
GAD
OCD
67% of patients with
Obsessive–Compulsive
Disorder4
42% of patients with
Generalised Anxiety
Disorder3
Kessler et al. Arch Gen Psychiatry 1995; DSM-IV-TR™ 2000; Brawman-Mintzer et al. Am J Psychiatry 1993;
Rasmussen et al. J Clin Psychiatry 1992 ; Dunner, Depression and Anxiety 2001
28
Outcome of Depression Treatment
The Five Rs
Reproduced with permission from Kupfer DJ. J Clin Psychiatry.
1991;52(suppl 5):28-34. Copyright 2002, Physicians Postgraduate
Press.
29
21st Century Medicine
30
Etiology of Major Depression
• Over a third of the liability for developing MDD
comes from genetic factors
• Genes likely mediate risk as well as resilience
• Environmental stressors interact with genes to
influence the likelihood of developing MDD
31
Genetics and Environmental Factors
• Studies of identical twins have
Strong
revealed that some conditions, such
Genetic
as psoriasis, have a strong genetic
Influence
component and are less influenced
by environmental and lifestyle
Psoriasis
factors—identical twins are more
MDD
Bipolar disorder
likely to share these diseases; but
IQ
Schizophrenia
other conditions, such as MS, are
only weakly influenced by genetic Neurotic/
extrovert
makeup and therefore twins may
Asthma
Diabetes
show differences depending on
their exposure to various
Cardiac
conditions
environmental factors
• “We used to think our fate was in
our stars. Now we know, in large
measure, our fate is in our genes.”
—J. D. Watson
Chakravarti A, Little P (2003), Nature 421(6921):412-414
Multiple
sclerosis
Cancers
Weak Genetic
Influence 32
Depression
anxiety are
are ultimately
ultimatelyabout
about
Depression and
and anxiety
how
to the
the environment
environment
howthe
thebrain
brainresponds
responds to
cognition
The Wisconsin Card Sorting Task
mood and anxiety
disorders
temperament
Genes:
Cells:
Systems:
Behavior:
sequence
variants and
variable gene
processing
molecular
pathways
activity in emotion
processing circuitry
Clinical phenotype
33
Risk Factors for Depressive Disorders
•
•
•
•
•
•
•
•
•
•
•
Family History of depressive disorders
Prior personal history of a depressive disorder
Female gender
Life stressor (eg, bereavement, chronic financial problems)
Certain personality traits
Loss of parents at an early age
Childhood abuse
Alcohol or drug abuse
Anxiety disorders
Neurologic disorders (eg, Parkinson’s, Alzheimer’s, stroke)
Primary sleep disorders
Hirschfeld RMA, Goodwin FK. In: The American Psychiatric Press Textbook of Psychiatry. 1987: 403-441
Depression Guideline Panel. Depression in Primary Care: Volume 1. Detection and Diagnosis. 1993: 1-65
34
Depressive Disorders: The Essentials
Stress is an important risk factor for depression
Early life stress is an important risk factor
Genes account for a substantial variation in risk
Brain systems related to the regulation of emotion are
functionally impaired during an episode
Monoaminergic drugs are therapeutic
35
Neurotransmitters and Depression
• There are disturbances in the monoamine systems
– Serotonin (5-hydroxytryptamine, 5-HT)
– Norepinephrine (NE)
– Dopamine (DA)??
• There are also disturbances in other
neurotransmitter systems (e.g., corticotropinreleasing factor [CRF] and substance P)
• Serotonin and norepinephrine have been the
most extensively studied in the clinical setting
36
Axon Terminals of Serotonergic Neurons
Project to Virtually All Portions of the Brain
Thalamus
Striatum
Neocortex
Cingulum
Cingulate Gyrus
To Hippocampus
Ventral Striatum
Amygdaloid Body
Hypothalamus
Cerebellar Cortex
Olfactory and
Intracerebellar Nuclei
Entorhinal
Caudal Raphe Nuclei
Cortices Hippocampus
Rostral Raphe Nuclei To Spinal Cord
Kaplan HI, Sadock BJ (1991), Synopsis of Psychiatry: Behavioral Sciences, Clinical Psychiatry, 6th ed. New York: Lippincott Williams & Wilkins
37
38
39
Serotonin Transporters Measured
With 123I -CIT and SPECT
5-HTT
5-HTT
Sagittal Image Through
Brainstem and Basal
Ganglia
Coronal Image
SPECT = single photon emission-computed tomography
40
Reduced Brainstem [123I]β-CIT
Binding in Depression
6
Brainstem V3"
Drug free
5
Drug naive
4
3
2
1
Healthy
Depressed
*p=0.02; V3" = [brainstem-occipital]/occipital; Malison RT et al. (1998), Biol Psychiatry 44(11):1090-1098
41
Influence of Life Stress on Depression
0.7
Probability of Major
Depression Episode
• Results of regression
analysis estimating the
association between
childhood maltreatment
(between the ages of
3-11) and adult
depression (ages 1826), as a function of
5-HTT genotype
0.6
0.5
s/s
s/l
0.4
0.3
l/l
0.2
0
No
Probable
Severe
Maltreatment Maltreatment Maltreatment
Caspi A et al. (2003), Science 301(5631):386-389
42
43
Dopamine and Depression
• Role of dopamine neurons in behavioral and physiological
areas altered in depression
• High rate of comorbidity of Parkinson’s disease
and depression
• Pathophysiological involvement of DA systems
in depression
Imaging Studies
Postmortem Studies
Biological
Fluids Studies
• Role of DA circuits in the actions of antidepressants
 MAOIs
 Effects on the DA transporter
44
Dopamine Transporter Binding
Potential in Depression
Healthy
Depressed
Linear (healthy)
Linear (depressed)
Dopamine Transporter
Binding Potential
• Dopamine transporter
binding potential in
bilateral striatum is lower
in depressed patients.
Data was analyzed using
analysis of covariance
with age as a covariate,
examining effect of
diagnosis (effect of
diagnosis: F1,29 = 7.1,
p=0.01)
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
15 Age 35
55
Meyer JH et al. (2001), Neuroreport 12(18):4121-4125
45
Cg25-Frontal Interactions in
Negative Mood Regulation
Recovery With SSRI
Transient Sadness
FDG PET
CBF PET
R
F9
F9
F9
Cg25
Cg25
Cg25
+4z
Cg31
Cg31
- 4z
Cg25
Cg25
Cg25
Depressed Patients
Healthy Volunteers
FDG = [18F] fluorodeoxyglucose; Numbers (i.e., 25, 31) are Brodmann area designations; Mayberg HS et al. (1999), Am J Psychiatry 156(5):675-82
Mapping Treatment Effects: Isolate
Potentially Most Relevant Regions
Paroxetine
(Paxil)
N=13
Age 36+10
HAM 22+3
post 6+4
F9
- dec
mF9
F9
Cg24
mF9
F9
mF10
pCg
+inc
Cg25
hc
P40
CBT
N=14
Age 41±9
HAM 20±3
post 6.7±4
th
th
vF
hc
hc
Cg24
pCg
F11
Different Treatments; Different Targets
HAM = HAM-D Score; P = inferior parietal; th = thalamus; hc = hippocampus; pCg = posterior
cingulate; mF = medial frontal; vF = ventral prefrontal; Goldapple K et al. (2004), Arch Gen
Psychiatry 61(1):34-41
Miller et al (2009) Biol Psychiatry 65:732-741.
48
PTSD Symptom Score (PSS)
Current Treatment Options
for Depression
Goal = reduce symptoms of depression and return patient
to full, active life
Nonpharmacologic
• Psychotherapy
- Cognitive behavioral therapy
- Interpersonal therapy
- Psychodynamic therapy
• Electroconvulsive therapy
• Phototherapy
Pharmacologic
• Antidepressant
medications
Depression Guideline Panel. Depression in Primary Care: Vol 1.
Detection and Diagnosis. Clinical Practice Guideline No. 5. 1993.
49
Binder et al (Submitted)
Potential Consequences of
Failing to Achieve Remission
• Increased risk relapse and treatment resistance
• Continued psychosocial limitations
• Decreased ability to work and decreased workplace
productivity
• Increased cost for medical treatment
• Sustained risk suicide, substance abuse
• Sustained depression can worsen morbidity/mortality of
other conditions
Paykel ES, et al. Psychol Med. 1995;25:1171-1180; Thase ME, et al. Am J Psychiatry. 1992;149:1046-1052.
Judd LL, et al. J Affect Disord. 1998;59:97-108; Miller IW, et al. J Clin Psychiatry. 1998;59:608-619.
Simon GE, et al. Gen Hosp Psychiatry. 2000;22:153-162; Druss BG, et al. Am J Psychiatry. 2001;158:731-734.
Frasure-Smith N, et al. JAMA. 1993;270:1819-1825; Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221-227.
Rovner BW, et al. JAMA. 1991;265:993-996.
50
THE NEED FOR OUTREACH TO COLLEGE STUDENTS
Only 15-19% of students who die by
suicide had been treated at campus
counseling center (Gallagher, Annual
Survey of Counseling Center
Directors, 1995-2006)
Why is this figure so low?
51
BARRIERS TO HELP-SEEKING
 Negative attitudes toward treatment
 Fear of negative reactions from parents, friends
 Concerns about confidentiality and potential
impact of treatment on academics and career
 Concerns about administrative sanctions
 Worries about costs/issues with parents’
insurance
 Beliefs that problems will resolve on their own
 Perception that problems don’t impact
functioning
 Resistance to giving up “control” of own
choices
 Too overwhelmed to take necessary steps
52
CONFIDENTIALITY AND NEGATIVE CONSEQUENCES
 “This may sound silly but it has held me back
from trying to talk to someone earlier: are
there any repercussions for coming in? Last
year I overdosed on a bunch of pills and I cut
up my body. My father flew down here to kind
of help me out…he said that it was probably a
good thing that I did not go to the hospital
because they would have to report a suicide
attempt or something and it could get me
kicked out of school. If I admit to that or talk
about my depression will I get in trouble?”
53
COST
 “I wouldn’t mind meeting you…One thing is
bothering me, though: my parents used to pay
for my therapists back home, but if I tell them
now that I’m thinking of going back to therapy
they would get really worried about me and
might want me to withdraw or something…But
then, I wouldn’t be able to pay on my own if it’s
as expensive as seeing private psychiatrists
were…What do you think I should do?”
54
DIALOGUE AS THERAPY
 ”I’ve had a really bad year and it seems like I am either super
happy or super sad, like right now I am sitting here crying on my
bed and I couldn’t even tell you why exactly…I think what I am
most stressed out [about] (which makes me contemplate
whether I should even live any more or not) is really stupid and
even I can recognize that it is dumb. I feel like I am so lost
because I am so undecided about my future that I lose sleep at
night. My parents will not stop bugging me about a major or a
career and I’m beginning to think that no matter what major or
career I choose I will hate it. My friends would probably never
guess I’m depressed. I try very hard to hide it…but in the end it
makes it worse because I feel like I’m not being who I really am. I
think the depression questionnaire was a God-send before I did
something stupid. People looking at my life from the outside in
would see a very normal happy childhood and I have a great
family and people who love me, so I almost feel guilty about
being so sad. I don’t have a real reason to be I guess... This is
really long, but it’s nice to get it all out. Thanks for listening.”
55
STUDENTS CAN COME BACK FOR HELP AT LATER DATE
 I filled out your survey last semester. You
emailed me multiple times, but I thought I had a
handle on things and was starting to feel better.
My friend committed suicide last week and I am
finding it really hard to even get out of bed. It’s
just,… I don't know. I thought I could handle this
on my own, but I may need help.
56
STEPS: Factors to Consider in
Antidepressant Selection
•
•
•
•
•
Safety
- Drug-drug interaction potential
Tolerability
- Acute and long term
Efficacy
- Onset of Action
- Treatment and prophylaxis
Payment (cost-effectiveness)
Simplicity
- Dosing
- Need for monitoring
Preskorn SM. J Clin Psychiatry. 1997; 58(suppl 6): 3-8.
58
Pharmacotherapy of Depression
Antidepressant agent classes
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic (TCAs) and tetracyclic
•
•
antidepressants
Selective serotonin reuptake inhibitors
(SSRIs)
Atypical antidepressants
- Bupropion
- Venlafaxine
- Nefazodone
- Mirtazapine
Rossen EK, Buschmann MT. Arch Psychiatr Nurs. 1995; 9: 130-136.
59
Benefits of Remission
•
•
•
•
Better prognosis
Better function
Less treatment resistance
Better outcomes in comorbid general medical
conditions
• Fewer complications
– Substance abuse
– Relationship problems
– Lower morbidity from general medical
conditions
60
Depression: Recurrence Risks
1 Episode
50%
2 Episodes
80% - 90%
3 Episodes
>90%
Depression Guideline Panel. Depression in Primary Care, Volume 2: Treatment of Major Depression.
Clinical Practice Guidelines, Number 5. 1993.
Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28-34.
61
Optimizing current treatments
• ECT effective for depression1
– Limitations include side effects and high
relapse rate (even with continuation ECT)2
– Increasingly focal ECT may be efficacious
with fewer side effects3,4
• Magnetic seizure therapy
– Convulsive therapy with a very focal initial
stimulation
– Preliminary efficacy suggested with fewer
cognitive side effects than ECT5,6
1The UK ECT Review Group, Lancet, 2003; 2Kellner et al., Arch
Gen Psychiatry, 2006; 3Sackeim et al., Arch Gen Psychiatry, 2000;
4Bakewell et al., J ECT, 2004; 5Lisanby et al.,
Neuropsychopharmacology, 2003; 6White et al.,
Anesth Analg, 2006
62
Remission Is Associated with
Fewer Missed Work Days
Mean days of work missed
18
16
14
12
10
8
6
*
4
2
0
Persistent†
Improved†
Remission†
*P<0.001
†Clinical depression status at 12-month assessment. Persistent = still meeting diagnostic criteria for MDD;
Improved = HAM-D 8, but not meeting diagnostic criteria; Remission = HAM-D 7
Simon GE, et al. Gen Hosp Psychiatry. 2000;22:153-162.
63
Depression Decreases
Workplace Productivity
• Absenteeism may represent only a small
fraction of the cost of depression in the
workplace
• Persistently depressed workers are 7 times
less productive on the job
• Impact of depression on function at work is
substantially higher than its association with
missed days at work
Druss BG, et al. Am J Psychiatry. 2001;158:731-734.
64
Depression Worsens Outcomes of Many
General Medical Conditions
• Depression worsens morbidity and mortality
after myocardial infarction1,2
• Depression increases risk for mortality in
patients in nursing homes3
• Depression worsens morbidity post-stroke4
• Depression can worsen outcomes of cancer,
diabetes, AIDS, and other disorders5
1.Frasure-Smith N, et al. JAMA. 1993;270:1819-1825. 2. Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221227. 3. Rovner BW, et al. JAMA. 1991;265:993-996. 4. Pohjasvaara T, et al. Eur J Neurol. 2001;8:315-319. 5.
Petitto JM, Evans DL. Depress Anxiety. 1998;8(suppl 1):80-84.
65
Depression Increases Risk of Cardiac
Mortality
RR cardiac mortality
(and 95% CI)
5
4
Nondepressed
Minor depression
Major depression
3
2
1
0
No pre-existing cardiac disease
Pre-existing cardiac disease
Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221-227.
66
Vagus Nerve Stimulation (VNS)
• FDA-approved (1997) for
treatment of medicationrefractory epilepsy
• FDA-approved (2005) for
treatment of depression that
has not responded to four or
more medications
• Achieved by implanting a
pulse generator attached to
(usually) the left vagus nerve
67
rTMS
• Studied for treatment of depression since 1993
– Multiple open and sham-controlled studies have been
performed; meta-analyses support antidepressant
effects for high frequency left-sided rTMS1,2
– Some studies have suggested a favorable
comparison to ECT, but data are mixed3,4
– Low frequency right-sided rTMS may also have
antidepressant effects5,6
• Side effects are generally mild; serious adverse
events (seizures) from TMS performed within
current safety guidelines are very rare7
1Holtzheimer et al., Psychopharm Bull, 2001; 2Kozel et al., Journal of Psychiatric Practice, 2002; 3Grunhaus et al., Biol
Psychiatry, 2000; 4Eranti et al., Am J Psychiatry, 2007; 5Fitzgerald et al., Arch Gen Psychiatry , 2003; 6Januel et al., Prog
Neuropsychopharmacol Biol Psychiatry, 2006; 7Wassermann, Electroencephalogr Clin Neurophysiol, 1998
68
Geracioti et al (2006) AJP 163:637-643.
69