Transcranial Magnetic Stimulation Therapy 1 The Future Direction of Neuropsychiatry

Transcranial Magnetic Stimulation Mechanism: To target and modulate neuroplasticity to influence behavior consequences. Neuroplasticity: the brain’s ability to reorganize itself by forming new neural connections throughout life. It allows the neurons in the brain to compensate for the injury and disease, and to adjust their activities in response to new situations or to changes in their environment.

Transcranial Magnetic Stimulation Brain reorganization takes place by mechanisms such as “axonal sprouting” in which undamaged axons grow new nerve endings to reconnect neurons whose links were injured or severed. Undamaged axons can also sprout nerve endings and connect with other undamaged nerve cells, forming new neural pathways to accomplish a needed function. In order to reconnect, the neurons need to be stimulated through activity. Neuroplasticity allows us to compensate for irreparably damaged or dysfunctional neural pathways by strengthening or rerouting our remaining ones.

Transcranial Magnetic Stimulation “Compensatory Masquerade” brain injury cases, cognitive disability. Allows already-constructed pathways that neighbor a damaged area to respond to changes in the body’s demands caused by lost function in some other area. “Homologous Region Adoption” allows one entire brain area to take over functions from distant brain areas that has been damaged. Cross model reassignment allows the brain of a blind individual in learning to read Braille, to rewire the sense of touch so it replaces the responsibilities of vision in the brain areas linked with reading. 4

Use it or Lose it! Neuroplasticity throughout life span: “use it or lose it” New research indicates that human brain cells are able to regenerate new brain cells even into the golden years of age 70 and beyond if one’s brain is constantly challenged by and engaged with a variety of stimulations and new experiences. 5

Plasticity The capacity of the brain to change with learning is known as plasticity. The brain may change in two aspects: 1. internal structure of the Neurons; area of synapses. 2. increases in the number of synapses between neurons. 6

Faraday’s Principle It is the electric stimulation via magnetic induction, not the magnetic field, that does the effect, thus passing current through the coil of the wire and then inducing the magnetic field. Induced currents are critical to the rate of change of the current, known as “Michael Faraday’s principle” I. The rate of change matters. The speed of the current affects the depolarization of neurons. II. Orientation of the coil-critical-neural elements perpendicular to the plane of the coil, using bidirectional pulses. 7

TMS History At first, TMS was developed by Barker et al. It was used as a brain mapping tool, as a tool to measure cortical excitability, as a probe of neuronal networks, and as a modulator of brain function. 8

Low Frequency vs. High Frequency TMS Concept of Depolarization Function Low Frequency Stimulation--inhibitory, more focal effect High Frequency Stimulation--facilitatory, multiple, spread out, global “dendritic, axonal effect”. When higher frequency rTMS is applied, a longer lasting effect can be induced which is thought to result from a long term potentiation (LTP), or depression (LTD) at the neuronal level. 9

What Could TMS Treat? I. Psychiatry: Depression (FDA approval, Oct 2008), treatment refractory cases, co-morbid, Panic DO, OCD, PTSD, Addiction (pathologic gambling), food, other substances cocaine, opiates, nicotine, schizoaffective disorder. II. Chronic neuropathic pains, phantom pain, fibromyalgia, Migraine headaches, Tourette's, tinnitus, painful dystonia. III. Neurology: Rehabilitation- after stroke, recovery-Aphasia, Neglect, Brain Injury, Seizures

Transcranial Magnetic Stimulation For MDD patients who have not adequately benefited from prior medication treatment attempts New treatment recently cleared by FDA –Has been studied by researchers for 20+ years Works by using MRI-strength magnetic field pulses Activates nerve cells in the brain, causing them to normalize neurotransmitter function Non-systemic and non-invasive –Does not circulate in the blood throughout the body –Does not involve surgery 11

Transcranial Magnetic Stimulation In an open-label trial (most like real world clinical practice), –1 in 2 had a significant improvement in symptoms –1 in 3 had complete symptom resolution Patients also experienced significant improvement in anxiety, appetite changes, aches and pains, and lack of energy associated with depression Over 10,000 procedures performed in clinical trials No systemic side effects such as weight gain, sexual dysfunction, nausea, dry mouth, and sedation 12

NeuroStar TMS Therapy Positive Value Proposition Significant chance of improvement (1 in 2) –Despite not having adequately benefited from previous treatment attempts No systemic side effects, such as weight gain and sexual dysfunction Non-invasive, no anesthesia, no sedation Favorable benefit/risk ratio compared to alternatives Associated with less hospitalizations, doctor visits, drugs, etc. 13

FAQs—Clinical 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 How 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 headache –Decreased significantly after the 1 st week of treatment 14

FAQs—Financial (cont.) How much does it cost? –Recommend speaking about cost for acute course, not per treatment Some will require more treatments, others less –Put it in context with the cost of other treatments Acute course of ECT is ~$18,000 Acute course of a branded drug combination is ~$2,000 –Provides good value for the money Significant chance of improvement (1 in 2) No systemic side effects Non-invasive, no anesthesia, no sedation Favorable benefit/risk ratio compared to alternatives Associated with less hospitalizations, doctor visits, drugs, etc. 15

Indication Statement NeuroStar TMS Therapy ® is indicated for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode Revision A

Fair Balance Statements NeuroStar TMS Therapy is contraindicated in patients with implanted metallic devices or non-removable metallic objects in or around the head As with any antidepressant treatment, patients should be monitored for symptoms of worsening depression NeuroStar TMS Therapy has not been studied in patients who have not received prior antidepressant treatment Efficacy has not been established in patients who have failed to receive benefit from two or more prior antidepressant treatments at minimal effective dose and duration in the current episode The most common adverse event related to treatment was scalp pain or discomfort Revision A

New APA Guidelines and CPT Coding APA GUIDELINES Transcranial magnetic stimulation is now listed in the American Psychiatric Association’s 2010 “Practice Guideline for the Treatment of Patients with Major Depressive Disorder” It is listed as an acute phase treatment option for patients who do not respond adequately to pharmacotherapy. This recent guideline states; “Acute phase treatment may include pharmacotherapy, depression-focused psychotherapy, the combination of medications and psychotherapy, or other somatic therapies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or light therapy.” (APA Guidelines 2010; Pg 46). CPT CODING Effective January 01, 2011, the American Medical Association has elevated the current codes to Category I CPT codes. The new codes are published as for a treatment planning session, and for treatment delivery and management per session. 18