1) PineWood TMS is a transcranial magnetic stimulation clinic located in Brattleboro, Vermont. It was founded by Julie Plummer, a psychiatric nurse and CEO, to provide alternative treatment for depression.
2) TMS works by using magnetic pulses to directly stimulate neurons in the brain and release neurotransmitters, targeting the circuits involved in mood without systemic side effects.
3) At PineWood TMS, nurses play a key role in assessing and educating patients, overseeing their treatment, and monitoring outcomes under a psychiatrist's supervision.
4. Neuro-Modulation Programs
in the North East
Legend
PineTree= PineWood TMS, Brattleboro, VT
Red Dots= TMS
Magenta= ECT + TMS
Blue Dots= ECT
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5. Many Patients with Depression Remain Poorly Served:
14 Million US Adults
7.2 Million 6.8 Million
Treated Untreated
Inadequate response
3.2 Million 4 Million Intolerant to side effects
Adequately Poorly
Treated Served
Kessler RC et al. JAMA. 2003;289(23):3095-3105.
6. Major Depressive Disorder
“Adequate” Treatment
Is Difficult to Achieve
Adequate Dosage Adequate Duration
Factors contributing to inadequate treatment include:
Lack of Poor
Efficacy Tolerability
Nonadherence Safety Issues
Comorbidities
1. Nemeroff CB. Depress Anxiety. 1996/1997;4(4):169-181; 2. Oquendo MA et al. J Clin
Psychiatry. 2003;64(7):825-833; 3. Oquendo MA et al. Am J Psychiatry. 1999;156(2):190-194.
October 17, 2011 6
7. Neuro-anatomy and physiology
of Major depressive disorder
anterior
HIGH prefrontal cingulate
cortex cortex
striatum
Neural
Activity
hypothalamus
thalamus
LOW
brainstem
neurotransmitter
In MDD, some centers
amygdala
areas of the
hippocampus
brain are
hypoactive and
others are
hyperactive.
7
October 17, 2011
8. Major Depressive Disorder:
Circuits and Neurotransmitters
concentration
pleasure/ psychomotor fatigue (physical)
interests pleasure/interests
psychomotor When there is an
fatigue (mental) appropriate
monoamine • Monoamine
sleep
Regions implicated in MDD are amount of
neurotransmitter dysfunction is
guilt appetite
connected to the brainstem via monoamine
projections linked to MDD
suicidality monoaminergic circuits neurotransmitter
worthlessness
•activity, neuronal
Malfunctioning
mood activity
circuits lead to
throughout the
specific
brain functions
symptoms
guilt normally.
suicidality
worthlessness
mood
Monoamine Serotonin (5-HT) Dopamine (DA) Norepinephrine (NE)
Neurotransmitters 8
9. Chemical Antidepressants
Antidepressant
Antidepressant
Therapeutic Effects such as:
increased
concentration blurred vision insomnia
agitation dry mouth fatigue
insomnia nausea blood
pressure
GI changes
distress
sexual
dysfunction weight gain
improved
mood
reduced feelings of
guilt, suicidality, and weight gain
worthlessness
9
10. APA Accepted Treatment
Algorithm for MDD 10M Primary Care
Psychiatry
• Initial Diagnosis
• Improved Diagnosis
8M • Early Treatment
Attempts • Improved Dosing
• Psychotherapy
Number of MDD Patients
• New Treatment
6M Options
4M
Combination & Augmentation
– Atypical Antipsychotics
SSRI – Mood Stabilizers
2M
SNRI
NDRI
MAOI & TCA
ECT VNS
TMS
0 1 2 3 4 5 6 7 8
Failed Treatment Attempts in Current Episode
Treatment-Resistance Continuum
Kessler RC et al. Arch Gen Psychiatry. 2005;62(6):617-627; Kessler RC et al. JAMA.
2003;289(23):3095-3105; Herrmann RC. Am J Psychiatry. 1995;152(6):869-875.
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13. Transcranial Magnetic Stimulation
Therapy System
Treatment coil
Head support unit
Touchscreen
Mobile console
Treatment chair
13
NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA; 2008.
15. TMS Directly Depolarizes Cortical
Neurons
Depolarization leads to action
potentials in local neurons and
thereby releases neurotransmitters
Pulsed magnetic fields
Neuron from TMS Coil:
• induce a local electric
current in the cortex
which depolarizes
neurons
Neurons are • elicit action potentials
“electrochemical • cause the release of
cells” and respond to chemical
either electrical or
neurotransmitters
chemical stimulation
15
16. TMS Releases Neurotransmitters
in the Brain
Depolarization of neurons Depolarization of pyramidal Activation of deeper brain
in the DLPFC causes local neurons in the DLPFC causes neurons then exerts secondary
neurotransmitter release neurotransmitter release in effects on remaining portions of
deeper brain neurons targeted mood circuits
Dorsolateral
prefrontal
cortex
Cingulate
cortex
Kito (2008) J Neuropsychiatry Clin Neurosci
These effects are
associated with
improvements in
depressive symptoms
16
17. TMS Mechanism of Action Summary
TMS Therapy:
Specifically targets the underlying brain circuits
involved in mood regulation
Directly depolarizes cortical neurons and
modulates neurotransmitter release in the brain
Effects involve both the local and deep neural
circuits in the brain
Accomplishes these effects without unwanted
systemic adverse effects
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18. Feature-Benefits Table
Features Benefits
No Anesthesia Physiological, psychological,
logistical
Non-Systemic Minimal side effects, no
memory loss or confusion
Non-Invasive TMS is not disfiguring
Concurrent use of Potentiate Positive Outcomes
other therapies
18
20. The Clinical Role of Psychiatric RNs in TMS
• Initial patient
assessment
• Education
• Establish therapeutic
treatment setting
• Observe therapy
• Assess patient
outcomes
20
21. Process for Patients Entering
PineWood TMS
1. Referral.
2. Education.
3. Evaluation.
4. Informed Consent.
21
22. Process TMS When
Treatments are Ordered
1. Treatment Parameters Set.
2. Treatment Commences.
3. Weekly Assessment of Depression.
4. Psychiatrist is Updated Weekly.
22
23. Frequently Asked Questions
• What are the chances it will work?
• How long will it take to feel better?
• How long will the effect last?
• What are the side effects?
23
24. Contact Information
PineWood TMS
Supporting Integrated Wellness
167 Main Street
Brattleboro, VT 05301
802-246-1304
WWW.PineWoodTMS.com
Julie@PineWoodTMS.com
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Editor's Notes
Julie Plummer, RNGraduated from GCC AND Program 1998Private boarding schoolCommunityGeneral HospitalInpatient Mental Heath UnitECT for 4.5 years-> introduced to TMSprimarily cared for patients with acute mental health issues for 10 + yearsEducation Never EndsCPIACLSECTTMSReikiEFTNVCReceived TMS certification in May 2009Won BDCC Business Plan Competition June 2011
PineWood TMS PhilosophyThe pine’s strength in the face of adversity makes it symbolic of those who have become strong through suffering.Symbolically people living with depression are living through the depths of what appears to be lifeless winter. Pines are known for their endurance, steadfastness, resiliency, even in the most harsh weather conditions. Pines are evergreen, ever full of life because no matter the weather around them (wind, snow, ice or rain), their needles remain green and full of life.Ah, but hope continues as the pine endures because after long-suffering, steadfast friendships and fame endure. In many traditions, they are associated with life, longevity and immortality, suggesting tranquility, faithfulness, and integrity. As a Christmas symbol, the tree was also a symbol of communication and mediation between heaven and earth because its roots reach into the earth and its branches soar into the heavens.After meditation and communication, peace is found. Among Native Americans it is known as Haudenosaunee, the Tree of Peace. The Chinese recognize pines as symbols of friendship in adversity.Interestingly, its essence has been used to treat despondency, despair, and self-condemnation. And pine resin and needles have been used medicinally to treat respiratory problems (in traditional Chinese medicine the lungs have long has associated with grief, something people suffering with depression often can relate to).This program has been named PineWood TMS to honor the inner core strength people need to recognize as they overcome depression.
Psychiatric prescribers and patients have asked about alternative treatment options treating depression
CLICK There are several brain regions known to play a role in the regulation of mood (Stahl 2008, pp. 492-499). This slide shows a general “neuroanatomy” of major depression. Neuroimaging studies of patients during an episode of major depression, and following recovery from depression, have shown specific patterns of change in the metabolic activity of these different regions. CLICKA reduction in activity is seen in many areas, including the left dorsolateral prefrontal cortex, and deeper areas including the amygdala and hippocampus (Epstein 2006, pp. 1786A, 1787A; Fu 2007, pp. 601A, 602A;Lee 2007, pp. 1489A, 1490A, B, 1491A; Lee 2008, pp. 781A, 782A, 783A). The rostral anterior cingulate cortex is unique among these brain regions in that its activity, as compared to the other major regions of the brain involved in depression, tends to be increased during executive tasks at a time when its activity should be decreased (Pizzagalli 2011, p. 196A). References:Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008.Epstein J, Pan H, Kocsis JH, et al. Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am J Psychiatry. 2006;163:1784-1790.Fu CHY, Williams SCR, Brammer MJ, et al. Neural responses to happy facial expressions in major depression following antidepressant treatment. Am J Psychiatry. 2007;164:599-607.Lee B, Cho SW, Khang HS, et al. The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder. ProgNeuropsychopharmacolBiol Psych. 2007; 31:1487-1492.Lee B, Seok J, Lee B, et al. Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder. ProgNeuropsychopharmacolBiol Psych. 2008; 32:778-785. Pizzagalli DA. Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response. Neuropsychopharmacology. 2011;36: 183-206.
The brain regions involved in MDD are connected to the brainstem through neuronal circuits. CLICK These regions are shown in purple on the figure (Stahl 2008, pp. 204A, 205A, 206A). CLICK The neuronal circuits connecting these areas release several monoamine neurotransmitters including dopamine, norepinephrine, and serotonin (shown here as purple circles, squares, and triangles). When there is an appropriate physiological amount of neurotransmitters being released within these neuronal pathways, communication among these brain regions is optimal, and the brain circuits function normally. CLICK However, it has been hypothesized that if the normal amount of neurotransmitters becomes reduced, depleted, or dysfunctional for some reason, depression may ensue (Stahl 2008, pp. 480A, 487A). In addition, there is a hypotheticallink between reduction of neurotransmitters in these regions and several symptoms key to a DSM-IV-TR diagnosis of Major Depressive Disorder (Stahl 2008, p. 491A). References:Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008.
CLICK Antidepressant medications are thought to treat MDD by chemically boosting the synaptic actions of one or more of the three monoamine neurotransmitters in these brain regions: dopamine, serotonin, and norepinephrine (Stahl 2008, p. 520A, B).However, because antidepressant medications are ingested and metabolized systemically (meaning they are absorbed through the gastrointestinal tract, distributed by the blood stream, and then metabolized, usually by the liver or kidneys), antidepressants may exert actions anywhere throughout the body. This means that they can elicit undesirable effects on sites both in the brain and throughout the body (Stahl 2008, pp. 531A, 547A).As shown on this slide, the result of these undesirable actions may be the development of a wide variety of medication side effects.CLICK References:Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008.
Important distinctions need to be made about TMS Therapy as compared to Electroconvulsive Therapy or ECT. TMS Therapy is NOT ECT. TMS is very different from ECT, both in terms of the technology itself and when it is appropriate for use.TMS Therapy is utilized much earlier in the depression care pathway than ECT.TMS Therapyis an office based procedure and is utilized after initial antidepressant medications have failed. In contrast, ECT uses direct electrical stimulation of the whole brain, requires anesthesia for delivery and is associated with cognitive side effects, some of which may be long term. TMS Therapy uses a focused electromagnetic field to stimulate a specific,targeted region of the brain. It does not require any sedation or anesthesia and has a mild adverse event profile. Because of the invasive nature of ECT and its side effects, ECT is usually reserved for patients who have exhausted most treatment options. Therefore, TMS, due to its targeted efficacy and mild adverse event profile is used much earlier in the treatment spectrum than ECT.
Movies with ”Hollywood Flash”- reinforce negative stigma of mental illness and ECT”One Flew Over the Cuckoo’s Nest” “A Beautiful Mind”“Girl Interrupted”ECT VideoPatients are carefully selected for ECT- it doesn’t treat Axis II, addictionsTimeTreatment Room for ~10 min.Recovery Room for ~ 30 min.Monitored and evaluated for 1 hour after leaving the recovery areaMemory lossDisorientation immediately following ECT typical of confusion after patients receive general anesthesiaLeast likely with RULMore likely in older patientsMany patients report improvement in their memory as their depressive symptoms resolve and they are better able to focus and concentratePatients can exhibit conditioned belief that they will always be depressed-Not uncommon for patients depressed for an extended time to doubt ECT is working (even if family and friends notice improvements in patient’s symptoms)
CLICK The underlying rationale for the use of TMS exploits the fact that neurons are electrochemical cells. This means that neuronal activity can be affected either chemically, via the use of drugs, or electrically, via interventions like TMS.Unlike drug action, whose effects tend to be anatomically diffuse, the effects of TMS are anatomically focused, and by design are non-invasive and non-systemic in action. Under normal conditions of use, TMS therefore incurs far fewer adverse events, and is devoid of undesired systemic adverse events commonly observed with antidepressant medications.The TMS device is a powerful electromagnet, which is turned on and off in a rapid fashion, producing a pattern of “pulsed” magnetic fields. The patient receives 40 pulses for 4 seconds with a 26 second interval repeated 75 times (trains) for a total of 3000 pulses per session.CLICK When pulsed magnetic fields are positioned close to an electrical conductor, like neurons, a local electrical current is produced in that conductor. This electric current is powerful enough right under the magnetic coil to elicit action potentials, which then travel down the neuron, ultimately causing the release of neurotransmitters at the synapse (Post 2001, p. 193A).References:Post A, Keck ME. Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms? J Psychiatric Research. 2001;35: 193-215.
When the pulsed magnetic fields from the TMS coil are applied to the left dorsolateral prefrontal cortex, there are a series of events that are thought to underlie the therapeutic effects of TMS in the treatment of major depression.First, direct neuronal depolarization under the coil leads to local action potentials in neurons and the local release of neurotransmitters in the cortex.CLICK In addition to these local effects, depolarization of cortical pyramidal neurons is thought to occur (as represented by the blue neural pathway), reaching to deeper brain regions that lie outside the direct action of the pulsed magnetic fields.Activation of these deeper brain regions is presumed to cause secondary activation of brainstem neurotransmitter centers, which results in upward influences on the remaining brain regions involved in mood regulation (represented by the purple neural pathway).CLICK As a result, dopamine (Kanno 2004, pp. 75A, 76A, 77A) and serotonin (Juckel 1999, pp. 393A, 394A) activity are increased in areas of the brain whose low neurotransmitter activity have been linked to depression. The net action of TMS, is therefore targeted on the specific brain areas known to be involved in the regulation of mood, and is comprehensive in that its action has both direct effects on local neurons in the cerebral cortex, and then results in deeper actions on brain regions that are distant from the site of stimulation, but neurally connected to these cortical areas.CLICK & CLICK These effects can be demonstrated in human neuroimaging studies of patients who have undergone treatment with TMS for their depression, as shown in the SPECT(single photon emission computed tomography) scan on the right (Kito, et al, 2008). In this image, the TMS coil has been positioned over the dorsolateral prefrontal cortex on the left side of the head. The area just underneath the coil is showing increased metabolic activity as a direct result of the magnetic stimulation. You can also see that the increase in metabolism reaches secondarily the deeper brain regions, in this case the regions of the cingulate cortex also show increased activation.CLICK The activity may be increased both in the short term by increasing release of neurotransmitters and in the long term by modulating expression of proteins involved in neurotransmitters signaling (Post 2001, p. 200A,B). Presumably, as a result of these changes, depression lifts (Slotema 2010, p. 876A). References:Kanno M, Matsumoto M, et al. Effects of acute repetitive transcranial magnetic stimulation on dopamine release in rat dorsolateral striatum. J Neurological Sciences. 2004;217:73-81.Juckel G, Mendlin MA, et al. Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output: Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression. Neuropsychopharmacology. 1999;21(3):391-398.Slotema CW, Blom JD, et al. Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010;71(7):873-884.Kito, S, Fujita, K, Koga, Y. Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression. J Neuropsychiatry ClinNeurosci. 2008; 20(1):74-80.
To summarize, TMS Therapy offers a unique mechanism of action unlike conventional antidepressant medication treatment.CLICK TMS Therapy specifically targets the underlying brain regions known to be involved in the regulation of mood. CLICK It works by direct depolarization of cortical neurons, and then CLICK by modulating the deeper brain regions which have a neuronal connection to these areas of the cortex.CLICK This allows TMS Therapy to effect both local and deep neural circuits – all without causing unwanted systemic side effects.Reference:NeuroStar TMS Therapy User Manual (Neuronetics, Inc., 2011).
no anesthesia, no sedationMedical-People suffering with depression are more likely to have other co-morbid medical concerns and issues (e.g. obesity, decrease liver and kidney function, substance abuse- including nicotine, alcohol, and other substances) making elective treatments with anesthesia several times a week less ideal. Also ECT does occasionally cause transient cardiac changes.Psychological- People who are severely depressed frequently also have PTSD due to histories a traumatic life events. Going under anesthesia can be especially difficult for people with PTSD, as it can bring up a lot of fears. While they are under anesthesia they are unaware of what’s going on around them. This sense of lack control can feel scary.Logistic- no escort needed. Symptoms exhibited by severely depressed patients can be misunderstand by family and friends. Consequently, these patients can alienate friends and family. Making arranging for an escort for difficult.Private, convenient treatment- No Stigma. People are often ashamed of their depression, as though they are to blame for it. Friends and family often unwittingly reinforce these beliefs. Non systemic- no side effects such as: weight gain, sexual dysfunction, nausea, dry mouth, or sedation, Seizures, adverse effect on cognitionNon- Invasive- no surgery, no voice changeOther Therapies- DBT, EFT, Music, Visualizations, Diaphragmatic Breathing- Improvement pts sense of self-empowermentTMS Therapy SummarySignificant chance of improvement (50% in clinical trials, 70-80% now being seen in clinical practice)Associated with less hospitalizations, doctor visits, drugs, etc.Favorable benefit/risk ratio compared to alternatives Fewer than 5% of patients discontinued due to adverse events -The most common adverse event related to treatment was scalp pain or discomfort TMS therapy for patients with MDD can easily be applied in psychiatrists’ clinical practices.Advances in TMS technology have taken it out of the hospital and into the psychiatrist’s officePatients can resume all normal activities immediately after each treatment sessionTMS is an “observed therapy,” meaning that a clinical professional, under the supervision of the attending psychiatrist, should be present during the treatment session
Complimentary Therapies can be used simultaneously while patient receive TMS include:Diaphragmatic BreathingMeditation VisualizationsMusic TherapyFocusingEmotional Freedom TechniqueReiki
Referral: Patient’s may self refer or call on recommendation of their out patient provider. Education: Welcome Packets contain:questionnaires regarding health, illness history, and demographics. BECK’s depression rating scale.Evaluation Appointment:Patient meets with MD and RN. Patient sits in the treatment chair to watch video and has the opportunity to ask questions.This appointment is an important part of the process to help insure that patient feels they have all the information needed to make an informed decision about TMS therapy.Psychiatric Evaluation:The psychiatrist reviews all referral forms in the charts of potential patientsDetermines if pt:Meets treatment criteria for TMSHas contraindications to TMSAssessment and discussion about how TMS will fit into treatment of patient’s depression.Prescribes a course of treatment Obtains signed Inform Consent formEstablishes treatment parameters
Motor Threshold DeterminationFirst treatment session requires determination of treatment settings. The first step requires isolating the area on the left Motor Cortex that elicits a right thumb twitch. This requires stimulation of the left motor cortex with multiple single magnetic pulses until right hand or thumb twitches are observed. This process determines the amount of magnetic energy required to stimulate the motor cortex.Once MT is determined the coil is placed over the prefrontal cortex 5.5 cm forward of this landmark. This area is believed to be over the limbic system (area that controls mood) and is the treatment site. Once parameters are recorded, treatment may begin.
What are the chances it will work?In open-label trial (most like real-world), 1 in 2 patients had significant improvement. 1 in 3 had complete symptom resolution In clinical practice 70-80% seeing improvementHow long will it take to feel better?May feel some improvement in 2 weeks, but most improvement will take 4-6 weeks.How long will the effect last? - In a 6-month follow-up study, patients received a single medication as maintenance treatment.Approximately 1/2 had symptom recurrence and required TMS re-treatment.Through the maintenance medication and the TMS re-treatment, less than 10% of patients relapsed.What are the side effects?Scalp pain or discomfort and headacheDecreased significantly after the 1st week of treatment