Transcript Vagus Nerve Stimulation What is it and how does it work?

Vagus Nerve
Stimulation:
A New Treatment for
Severe Depression
VNS@UW
UW Health /Meriter Hospital
Department of Psychiatry
February 1, 2006
CHRONIC
DEPRESSION
WHAT IS IT, HOW WE TREAT IT AND
THE ROLE OF VAGUS NERVE
STIMULATION
Stephen J. Weiler, M.D.
U.W. Health Psychiatry
DEPRESSION:
WHAT IS IT? DSM-IV CRITERIA
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DEPRESSED MOOD
ANHEDONIA
CHANGE IN APPETITE OR WEIGHT
INSOMNIA OR HYPERSOMNIA
PSYCHOMOTOR RETARDATION OR AGITATION
DECREASE ENERGY
GUILT OR FEELINGS OF WORTHLESSNESS
DECREASED CONCENTRATION
RECURRENT THOUGHTS OF DEATH OR SUICIDAL
IDEATION
Depression is a common illness
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Depression affects 18 million Americans at
any one time; 2/3 are female
20% to 35% of people with depression (at
least 4 million Americans) have long-lasting
or repeated episodes of depression that do
not respond or respond only temporarily to
several antidepressant treatments
THE “COST” OF DEPRESSION
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4TH MOST DISABLING CONDITION
WORLDWIDE; MOST DISABLING
CONDITION FOR FEMALES IN U.S.
LOSS OF PRODUCTIVITY IN WORK AND
FAMILY ROLES
WORSENS OTHER MEDICAL CONDITIONS
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INCREASES RISK FOR DEVELOPING OTHER
MEDICAL CONDITIONS
WORSE OUTCOMES
HIGHER COSTS
CHRONIC AND RECURRENT
DEPRESSION
Chronic depression: depression that
lasts 2 years or more without relief
 Recurrent depression: 2 or more
episodes of depression over time
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WHAT IS TREATMENT
RESISTANT DEPRESSION?
BASICALLY DEPRESSIVE STATES THAT DO
NOT RESPOND TO TREATMENT
STAGE 0: No single adequate trial of meds
STAGE 1: Failure to respond to 1 med trial
STAGE 2: Failure to respond to 2 different med trials
STAGE 3: Stage 2 + 1 augmentation trial
STAGE 4: Stage 3 + 2 augmentation trials
STAGE 5: Stage 4 + failure to respond to ECT
How effective are current
treatments?
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Mild to moderate depression: meds and
psychotherapy about equal with >60% response
rates
Moderate to severe depression: psychotherapy
alone ineffective
RECENT RESEARCH
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35% COMPLETE RESPONSE TO 1 SSRI
50% SIGNIFICANT IMPROVEMENT
ECT: ~80% RESPONSE RATE
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BUT HIGH RELAPSE RATE (64% in 24 weeks)
VAGUS NERVE STIMULATION
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A COMPLETELY NEW TREATMENT
APPROACH (more on this with Dr Halverson)
INDICATIONS (FDA Criteria)
VNS Therapy is indicated for the adjunctive longterm treatment of chronic or recurrent depression
for patients 18 years of age or older who are
experiencing a major depressive episode and have
not had an adequate response to four or more
adequate antidepressant treatments.
EXCLUSIONARY
CONSIDERATIONS FOR VNS
• CURRENT STATE THAT IS WITH HIGH
IMMEDIATE RISK (SUICIDE, SUBSTANCE
ABUSE, PROBLEMS WITH BEHAVIORAL
CONTROL)
 HISTORY OF BRAIN SURGERY OR
PROGRESSIVE NEUROLOGICAL D/O
 H/O SURGERY ON VAGUS NERVE
 SOME MEDICAL CONDITIONS
 OTHER FORMS OF CNS STIMULATION
DEVICES
Vagus Nerve Stimulation
Therapy
What is it and how does it work?
Jerry L. Halverson, M.D.
University of Wisconsin
Department of Psychiatry
Meriter Hospital
February 1, 2006
FDA Indication
•INTENDED USE/INDICATIONS – UNITED
STATES
•VNS Therapy is indicated for the adjunctive
long-term treatment of chronic or recurrent
depression for patients 18 years of age or
older who are experiencing a major
depressive episode and have not had an
adequate response to four or more
adequate antidepressant treatments.
What is VNS Therapy?
•VNS Therapy stands
for “Vagus Nerve
Stimulation”
•The vagus nerve:
– Is one of the primary
communication pathways from
the major organs of the body to
the brain
– Appears to communicate with
areas of the brain involved in
regulating mood
– Does not contain pain fibers
How VNS Therapy works
– VNS Therapy is delivered by a
pulse generator—a device like a
pacemaker
– The pulse generator sends mild,
intermittent pulses through a thin,
flexible wire leading to electrodes
attached to the left vagus nerve
– Because the vagus nerve does not
contain pain fibers, VNS Therapy is
typically painless
– VNS Therapy is regular, automatic,
and generally unnoticeable
– VNS Therapy is added to your
current antidepressant medications
What is the pulse generator?
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The device delivers very mild
intermittent brief pulses to the left
vagus nerve. 30s/5m
The pulses that are delivered to
the left vagus nerve are
transmitted to the central nervous
system, and they appear to go to
specific areas in the central
nervous system that control mood,
motivation, sleep, appetite, and
other symptoms that are relevant
to depression.
VNS Therapy targets specific
areas of the brain that affect the
production or activity of
neurotransmitters, such as
serotonin and norepinephrine.
What does the pulse generator look
like?
Why use VNS in depression?
• FDA approved for use in epilepsy in 1997
• More than 32,000 patients have been
treated worldwide with VNS for epilepsy.
• Clinical experience with comorbid patients
• Trials since the mid nineties
• FDA approval in July 2005
Why use VNS?
• Adding VNS Therapy has been shown to succeed when
other antidepressant treatments have not.
• The effectiveness of VNS Therapy improves over time
and lasts.
– After 1 year, 1 in 3 people receiving VNS Therapy experienced
significant mood improvements, compared with 1 in 8 people
receiving only other antidepressant treatments.
– Many people who did not respond immediately to VNS Therapy
did experience improvement over time.
– Most people who responded to VNS Therapy maintained
improvement for at least two years.
– For some people, VNS Therapy reduces the need for
antidepressant medications over time.
Clinical Trials and Published
Studies #1
• Patients included in VNS trials are typically
excluded from other antidepressant
studies
• Patients were experiencing long term
chronic or recurrent, treatment resistant
depression that had not responded to
multiple antidepressant treatment trials
including adequate medication trials,
therapy and electroconvulsive therapy
Thumbnail of the “average” trial
patient
• Experienced depression for more than 25
years
• Had current major depressive episode for
longer than four years
• Experienced more than 12 unsuccessful
clinical treatments for their depression
• 53% were previously treated with ECT
Clinical Trials and Published
Studies #2
• In studies published in peer reviewed
journals, after two years of adjunctive use
of VNS
– More than 50% realized at least a meaningful
clinical benefit
– Approximately 1/3 had realized at least a 50%
improvement in their depressive symptoms
– One out of every six patients were depression
free
Clinical Trials and Published
Studies #3
• In this treatment resistant, difficult to treat
population between 60 and 70% of
patients achieving response at 3 months
or one year maintained this response
• This durability of response is
unprecedented in other antidepressant
treatments, particularly in this difficult to
treat population
Quality-of-life benefits
•In addition to improvements in mood, many
people receiving VNS Therapy and their
physicians also report significant and lasting
improvements in:
–Vitality—increased energy
–Social functioning—increased interaction with
family and/or friends
–Emotional well-being—better function at work
and in daily activities
–Mental health—more positive feelings
Cost Considerations
• Chronic Depression is a very costly problem,
both to the patient’s quality of life and in the
cost of the treatments
• Many insurance companies are in the
process of determining coverage for VNS
therapy for chronic depression
• VNS Therapy has been paid for by insurance
companies on a case-by-case basis
• Cyberonics actively assists in this process
• Research and indigent programs
VNS Implant Surgery
P. Charles Garell, MD
Director of Functional Neurosurgery
Chief of Neurosurgery, VA Hospital
Surgical evaluation
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Meet with surgeon to review
Health history
 Physical exam
 Benefits of surgery
 Risks of surgery
 Details of the procedure
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You decide on surgery
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Talk to others who have had surgery.
Talk to insurance company.
Talk to friends and family.
Talk to psychiatrist (again), or medical doctor.
Work up
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Meet nurse practitioner.
Have blood work done.
Maybe chest x-ray and EKG.
Meet anesthesiologist.
Confirm surgical date
Surgery
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In the OR you will be under general anesthesia
(completely asleep).
You will be positioned with your neck and upper
chest scrubbed with antibacterial soap.
Sterile drapes will cover all but your left neck
and left upper chest.
Incision will be marked.
You will receive antibiotics.
Surgery
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Neck incision will expose the vagus nerve and
surrounding structures.
Upper chest incision will create a “pocket” for
the “battery pack.”
A wire will be passed under the skin from the
neck to the chest incision.
Surgery
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The wire (electrode) will be wrapped around the
vagus nerve. The other end will be connected to
the battery pack (internal pulse generator).
The system will be tested.
Both incisions will be sutured closed.
The VNS Therapy™ procedure is
straightforward
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Actual implant procedure takes about 1 hour
Usually performed under general anesthesia
Usually an outpatient procedure—no overnight hospital stay
Two small incisions:
3 months
post procedure
 One in the left chest area, below the collarbone for the pulse
generator
 One in a natural crease on the left side of the neck to connect with
the left vagus nerve
The incisions heal in about a week
The small scars fade over time, becoming barely noticeable for
many people
In-hospital recovery
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You will wake up in the recovery room, then
transfer to the hospital ward.
Bandages will be checked, pain will be treated,
and you will receive more antibiotics.
You will stay overnight and be discharged the
next morning.
At-home recovery
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You will be given pain medications to take by
mouth.
You will change you bandage at 3 days.
You will remove you bandage at 6 days.
You will be sore and tired but able to do most
normal activities.
Follow up
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At two weeks you will see Dr. Halverson to
activate your VNS system.
At six weeks you will see me to assess healing
progress.
Long-term
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Battery pack currently last about 5 years
(depends on stimulation parameters). At 5 years
it will need to be replaced if you want (if it was
helpful).
Battery replacement requires surgery, however,
this is done as an outpatient, with only one
incision.
After the implant
Management
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We will work with your psychiatrist to help you
feel, and stay, better.
VNS@UW will manage your implant, your
primary psychiatrist will continue to work with
your medications.
Two weeks after the implant, you will be seen in
our clinic for activation of the implant
You will be seen weekly and your dose titrated
higher until your VNS is at a therapeutic level
Implant Interrogation and Dosage
Adjustments
• Interrogation of the
implant and titration of
dose is done in the
office
• Usually finished within
15 minutes
• Simple and Painless
Side effects of VNS Therapy are mild to
moderate and typically decrease over time
– Side effects typically occur only during stimulation and may include:
• Temporary hoarseness or changes in voice tone, cough, tickling in the
throat, or a feeling of shortness of breath during exertion
• Some may complain of no side effects
– The side effects can be lessened by dose adjustments
– The side effects typically decrease over time
– VNS Therapy works with your other treatments without undesired
interactions
– VNS Therapy has not been associated with sexual dysfunction or
memory impairment, common side effects of other antidepressant
treatments1
– The incidence of sleep disturbance and weight gain (also commonly
reported side effects of other antidepressant treatments) is less than
2%
If necessary, you can control any
troublesome stimulation-related side effects
of VNS Therapy
•The VNS Therapy System
includes a small magnet that can
temporarily control any
troublesome side effects.
•You can hold or place the
magnet over your VNS Therapy
pulse generator to stop
stimulation temporarily during
situations or activities when even
mild side effects are troublesome.
For example:
– Public speaking
– Singing
– Exercise or other strenuous activity