Transcript Tariq J. Faridi, B. Sc, M. Ed. Director of Education

Transcranial Magnetic
Stimulation

Neurostar Treatment Device

Patient Introduction
Tariq J. Faridi, B. Sc, M. Ed.
Director of Education and Research, Visual Odyssey
Temple Georgia
Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006)
Am J Psychiatry; McGrath (2006) Am J Psychiatry
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Systemic Drug Side Effects

Weight Gain

Fatigue

Constipation


Diarrhea
Headache/
Migraine
Nausea


Abnormal
Ejaculation

Drowsiness

Impotence

Insomnia

Sweating

Decreased
Libido

Tremor
Nervous Anxiety



Increased
Appetite
Treatment
Discontinuation
Side Effects

Weakness

Dry Mouth

Dizziness

Decreased
Appetite
Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am
J Psychiatry; Neuronetics, Inc. (data on file)
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“The NeuroStar TMS System is indicated for
the treatment of adult patients with Major
Depressive Disorder (MDD) who have failed to
receive satisfactory improvement from one
prior antidepressant medication at or above
the minimal effective dose and duration in the
current episode…”
Nearly all patients received multiple ineffective
treatment attempts in current episode (range: 1 to
23 attempts, avg: 4)
Demitrack & Thase. (2009) Psychopharm Bull
Adapted from: Practice Guideline for the Treatment of Patients with Major
Depressive Disorder, 3rd Edition, APA (2010)
5
6
prefrontal
cortex
anterior
cingulate
cortex
striatu
m
hypothalamus
HIGH
thalamus
Neural
Activity
LOW
amygdala
brainstem
neurotransmitter
centers
hippocampus
In MDD, some
areas of the
brain are
hypoactive and
others are
hyperactive.
concentration
pleasure/
interests
psychomotor
fatigue
monoamine
(mental)
neurotransmitter
guilt
projections
suicidality
worthlessness
psychomotor fatigue
(physical)
pleasure/interests
sleep are
Regions implicated in MDD
appetite
connected to the brainstem
via
monoaminergic circuits
mood
guilt
suicidality
worthlessness
mood
Monoamine
Neurotransmitters
Serotonin (5-HT)
Dopamine (DA)
When there is
appropriate
• an
Monoamine
amount ofis
dysfunction
monoamine
linked
to MDD
neurotransmitter
• Malfunctioning
activity,
circuits lead
to
neuronal
activity
specific
throughout
the
symptoms
brain
functions
normally.
Norepinephrine (NE)
 The treatment coil
produces MRIstrength magnetic
field pulses.
 Magnetic field pulses
pass unimpeded
through the cranium
for 2-3 cm. and
induce a small
electric current.
 Induced electric
currents stimulate
the firing of nearby
neurons, causing the
release of
neurotransmitters
and clinical effects.
Faraday (1839) Experimental Research in Electricity. Vol 1; Barker 9(1991) J Clin Neurophysiol; Barker (1985) Lancet
Depolarization of neurons in
the DLPFC causes local
neurotransmitter release
These effects
Dorsolateral
are associated
prefrontal
cortex
with
Anterior
improvements
cingulate
cortex
in depressive
symptoms
Kito (2008) J Neuropsychiatry Clin Neurosci
Depolarization of pyramidal
neurons in the DLPFC also
causes neurotransmitter release
in deeper brain neurons
Activation of deeper brain
neurons then exerts secondary
effects on remaining portions of
targeted mood circuits
R
L
L
TMS Coil
R
Activation of fronto-cingulate brain circuit following a
course of TMS applied to the left dorsolateral
prefrontal cortex in patients with Major Depression
Kito (2008) J Neuropsychiatry Clin Neurosci

Only TMS device FDA-cleared for the treatment of depression

Non-invasive and non-systemic

The most common side effect associated with
treatment is scalp pain or discomfort –
generally mild to moderate

Outpatient procedure, can be performed in a
psychiatrist’s office; no anesthesia or sedation

37 minute treatment, administered daily
for 4-6 weeks

Observed therapy facilitates
adherence with treatment

Available by prescription only
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 No
systemic side effects
 No adverse effect on cognition
 Most common adverse event associated with
treatment was scalp pain or discomfort

< 5% of patients discontinued due to adverse events
 No
seizures with TMS during clinical studies
(over 10,000 treatments)

Six seizures reported with TMS in post-marketing period
(estimated risk of seizure < 0.1% per acute treatment course)
 Long
term safety demonstrated in 6 months
follow-up
Janicak, et al. J Clin Psychiatry, 2008; Janicak, et al. Brain
Stimulation, 2010.
John P. O’Reardon, H. Brent Sovason, Philip G. Janicak, Shirlene Sampson, Keith E. Isenberg, Ziad Nahas, William M. McDonald,
David Avery, Paul B. Fitzgerald, Colleen Loo, Mark A. Demitrack, Mark S. George, and Harold A. Sackeim
BIOL PSYCHIATRY 2007;62:1208-1216 ©2007 Society of Biological Psychiatry
Major Findings:
• N=301 patients (ATHF 1 thru 4),
23 sites
• 22.1% reduction in MADRS total
score with active NeuroStar TMS
vs 9.1% on sham at 4 weeks (in
ATHF = 1 population)
• Clinically meaningful effect size = 0.52
(in ATHF = 1 population)
• In open label extension study, 1 in 2
patients responded, 1 in 3 patients
achieved remission at 6 weeks
• Safety confirmed in 6 month follow-up
Conclusion: “Transcranial Magnetic Stimulation was effective in treating
major depression with minimal side effects reported. It offers clinicians a
novel alternative for the treatment of this disorder.”
Demitrack & Thase (2009) Psychopharm Bulletin
Mark S. George, MD; Sarah H. Lisanby, MD; David Avery, MD; William M. McDonald, MD; Valerie Durkalski, PhD;
Martina Pavlicova, Phd; Berry Anderson, Phd, RN; Ziad Nahas, MD; Peter Bulow, MD; Paul Zarkowski, MD;
Paul E. Holtzheimer III, MD; Theresa Schwartz, MS; Harold A. Sackeim, PHD
Major Findings:
• 30% of patients achieved
• NIMH-funded, independent of industry
• N=190 patients, 4 premier academic sites
remission in open-label
• Primary outcome measure:
extension phase
% Remission - Active 15% vs Sham 4% (P = • Excellent safety, nearly 90% of
0.015); Odds Ratio of achieving remission:
patients adherent to acute
4.2 (95%CI, 1.3-13.2)
phase treatment course
Conclusion: “Daily left prefrontal rTMS as monotherapy produced statistically
significant and clinically meaningful antidepressant therapeutic effects greater than
sham.”
 The
evidence for the clinical efficacy of
TMS in the treatment of depression is
considerable, spanning more than 30
controlled clinical research studies
 Most
recent meta-analysis (Slotema, et al, 2010):
Included analysis of 34 studies involving 1,383 patients
 Estimated standardized effect size = 0.55 (P < 0.001)
Conclusion: “…rTMS deserves a place in the standard toolbox of
psychiatric treatment methods, as it is effective for depression
…and has a mild side effect profile….”

Slotema, et al. J Clin Psych (2010)
• Safety confirmed during long term, open-label 6 month
follow up period
– During open-label follow up on antidepressant
medication monotherapy, ~37% of patients required
TMS reintroduction
– ~85% of patients who received TMS reintroduction
benefited
• Net incidence of illness relapse under these open-label
follow up conditions: 11%
– Six-month relapse with antidepressant treatment
alone in STAR*D study was 35-50% (Level 2 and 3
range)
Janicak, et al. Brain Stimulation, 2010.