TMS Therapy at Pilsen Wellness Center

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Learn more about NeuroStar TMS (transcranial magnetic stimulation) Therapy

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  • This video describes patient experiences with depression.
  • Looking at the entire world, we see that major depression is an enormous burden on society. In fact, in 2004 the World Health Organization rated unipolar major depression as the third most significant cause of disability worldwide…
  • …and they project that unipolar major depression will rise to the number one cause of disability by 2030. So clearly this is a very large problem that we need to wrap our arms around.
  • Given that so many patients experience intolerable side effects from current therapies without receiving adequate benefit, these patients are looking for effective alternatives. Now that we’ve discussed some of the issues confronting major depression sufferers and their doctors, I’d like to show you a proven approach to addressing these issues.
  • I’m here today to talk with you about the NeuroStar TMS Therapy – a non-drug approach to treating depression. The NeuroStar TMS Therapy system is a complete clinical system which uses a highly-focused pulsed magnetic field to stimulate nerve cells in the area of the brain that are thought to control mood. The NeuroStar system is cleared by the United States Food and Drug Administration for the treatment of major depression in patients who have not benefitted from initial antidepressant medication. Since FDA clearance in 2008, over 11,000 patients have been treated with NeuroStar TMS Therapy. Let’s watch a quick video to view a typical NeuroStar TMS Therapy treatment session.
  • NeuroStar TMS Therapy is an outpatient procedure that is delivered right in the physician’s office. During TMS treatment, the patient is seated comfortably in the treatment chair. At the first TMS session, the treating physician uses the NeuroStar treatment coil to perform a test to identify the proper treatment location on the patient’s head and to determine the correct magnetic field strength to be used during treatment. During this test, the physician is looking for the amount of magnetic field strength that results in a visible movement of the patient’s right thumb. This field strength, called the Motor Threshold, is customized for each patient to allow delivery of exactly the right dose for that patient. Once the patient’s Motor Threshold is determined and the patient’s corresponding dose parameters are set, the physician moves the treatment coil to the TMS treatment location over the left prefrontal cortex to begin the TMS Therapy treatment session. The NeuroStar system delivers the focused pulses of the magnetic field in a rapid 4 second burst, followed by a 26 second pause. A series of these 30 second intervals are delivered over a 37 minute period, delivering a total of 3000 pulses for a TMS treatment session. During TMS Therapy, the patient is awake and alert, and able to speak with the system operator whenever necessary. When TMS Therapy is completed, the patient is able to resume normal activities.
  • 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. A 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.
  • 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. A 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. These regions are shown in purple on the figure (Stahl 2008, pp. 204A, 205A, 206A). 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. 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 hypothetical link 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.
  • The brain regions involved in MDD are connected to the brainstem through neuronal circuits. These regions are shown in purple on the figure (Stahl 2008, pp. 204A, 205A, 206A). 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. 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 hypothetical link 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.
  • 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.References:Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008.
  • 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.References:Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008.
  • 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. 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 precisely pulsed magnetic fields from the NeuroStar 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.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).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 NeuroStar 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.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 NeuroStar 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.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 Clin Neurosci. 2008; 20(1):74-80.
  • To summarize, NeuroStar TMS Therapy offers a unique mechanism of action unlike conventional antidepressant medication treatment.NeuroStar TMS Therapy specifically targets the underlying brain regions known to be involved in the regulation of mood. It works by direct depolarization of cortical neurons, and then by modulating the deeper brain regions which have a neuronal connection to these areas of the cortex.This allows NeuroStar TMS Therapy to affect both local and deep neural circuits – all without causing unwanted systemic side effects.Reference:NeuroStar TMS Therapy User Manual (Neuronetics, Inc., 2011).
  • Before we speak further about the NeuroStar TMS Therapy system, there are important distinctions to make 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 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. TMS Therapy is 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. 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.
  • The NeuroStar system consists of: A Mobile Console – which houses the power electronics A Graphical Touch Screen User Interface – which allows users to easily operate the system An Integrated Treatment Coil – this is the high-powered magnetic treatment coil which, when placed on the patient’s head, delivers TMS Therapy to a specific brain region. A SenStar Treatment Link –an essential component which monitors and provides quality control for each treatment
  • The SenStar Treatment Link is another essential component of the system. The SenStar ensures that the treatment coil is functioning properly and is positioned correctly, confirming to you that your patients are receiving optimal treatment. As shown here, this single use device has multiple layers, each with a specific function designed for quality assurance. The first layer constitutes the “Sensory Guard”. This protective layer functions to reduce the intensity of the magnetic field at the scalp to improve tolerability of high-frequency stimulation, without affecting the deeper, therapeutic magnetic field in the brain. The second layer is the “Magnetic Field Detector” which contains a sensor that verifies the intensity of the magnetic field pulses being delivered before each treatment. This verification ensures that for every treatment, the patient receives exactly the pulses that you have programmed to be delivered, so to ensure delivery of safe and effective treatment.  This layer also contains a built-in “Smart Chip” that records each unique SenStar ID code for tracking. The Smart Chip also allows constant monitoring of the treatment status by providing a communication link between the SenStar and the NeuroStar system. The “Contact Sensing” layer uses micro sensors to constantly measure proper contact between the patient’s scalp and the treatment coil.  Even a small displacement of the TMS treatment coil from the patient’s head (e.g. 2 mm) can reduce the magnetic field in the brain to sub-therapeutic levels.  Sensors monitor every pulse for correct contact between the patient’s head and the coil and give you a visual feedback on the graphic user interface. This allows you the ability to make coil adjustments and re-administer missed pulses; ensuring patients receive the maximum stimulation of the target tissue.The last layer is a Hygiene Barrier which touches the patient’s head. It is latex-free and acts as a protective barrier between the patient’s head and the coil to maintain cleanliness and comfort.
  • First, let me introduce you to the maker of the NeuroStar TMS Therapy system – Neuronetics.Neuronetics was founded in 2003. We have a highly experienced management team that has successfully progressed the company from initial clinical trials to FDA clearance and now into seeing NeuroStar TMS Therapy come into place as a clinical standard of care for the treatment of major depression. We also have an expert clinical team spread across the country that’s here to educate and support TMS providers and their staff. When the company was founded, we licensed a family of patents from Emory University and have since added numerous others to that portfolio. There are currently a total of 21 TMS patents that protect the NeuroStar technology that we’ve just discussed. We’ve been very fortunate as a company to have the support of a large group of top-tier life-science investors. Their investment in Neuronetics and their belief in this opportunity for physicians and patients have made the NeuroStar technology, clinical development and now market development possible.
  • Neuronetics is a leader in TMS Therapy innovation. We are a privately held medical device company who pioneered TMS Therapy and made it a clinical reality. Our goal moving forward is to partner with healthcare professionals by providing them the best products and services possible. We are committed to continuous product improvement and to developing new and innovative solutions to meet our customers' needs. By providing these tools, we can help healthcare professionals achieve their ultimate goal of effectively treating the patients they serve.
  • So before we move onto rigorous randomized controlled trials that have been conducted in TMS, lets set the stage by first discussing the recent Agency for Healthcare Research and Quality (AHRQ) report which confirms the evidence base for efficacy of TMS. AHRQ is an independent government agency which conducted a peer-reviewed look at current antidepressant treatments. As a pre-review for this webinar, I’ve asked you all to read the execute summary of this report. Some of the key points are shown on this slide. The report included 15 clinical trials involving nearly five hundred patients The average HAMD decrease in depressive symptoms was greater than 5 points vs. sham treatmentdemonstrating that the treatment was not only statistically significant, but clinically significant as well. Response rates with active TMS were greater then 3 times as likely than sham treatment Remission rate with active TMS were greater than 6 times as likely than sham treatmentThe reports overall consensus was there was a high strength of evidence for the efficacy of TMS demonstrated from well-controlled randomized controlled trials.
  • One of the first major milestones that Neuronetics embarked on was the completion of a successful randomized controlled clinical trial. A rigorous monotherapy study design, The NeuroStar Clinical Development Program, was established to demonstrate that TMS Therapy was both safe and effective in the treatment of depression in patients who had not benefited from prior antidepressant treatment.The program consisted of three studies. The first was the Acute Efficacy & Safety Study. This randomized controlled, double blind trial started with 301 patients and was intended to compare active TMS to sham. Patients received either active or sham treatment for 4-6 weeks. If patients improved during this trial, they were able to move into the Durability of Effect Study where they were monitored for 6 months.If patients did not improve after 4 weeks in the Acute Efficacy and Safety Study, they had the option to move into the Open-Label Extension Study. All patients in this trial received active TMS Therapy and again, moved into the Durability of Effect Study if they improved. These three key studies form the basis for FDA-clearance of the NeuroStar TMS Therapy System.
  • We will start by discussing the NeuroStar TMS Therapy Randomized Controlled Trial – The Acute Efficacy & Safety Study conducted in a difficult to treat depression population (often referred to as study 101 or the O’Reardon study). This slide describes some of the trial designs – which was again a randomized controlled trial. All patients in this study had failed to benefit from prior drug therapy. So these were NOT naïve patients. Patients entering the study were washed of all prior antidepressant medication and then received TMS monotherapy. Patients enrolled had a primary diagnosis of DSM-IV unipolar, non-psychotic Major Depressive Disorder with moderate to severe symptoms at baseline.Overall, there were 301 patients enrolled in this controlled study. Initially, all patient data was submitted to the FDA for clearance of the NeuroStar system. However, after review by an FDA panel, it was decided that NeuroStar TMS Therapy was overall a safe therapy but was most effective for a subset of the resistant population – those that had failed one prior antidepressant medication of adequate dose and duration. So an analysis of that population, which totaled 164 patients, was completed. All patients enrolled within this indicated patient population group had extensive prior antidepressant drug exposure. These patients had tried and failed one initial drug treatment, administered at an adequate daily dose and duration without benefit. The average number of overall treatment attempts (which includes all medications given in the current episode, regardless of whether they reached an adequate dose and duration) was 4, with a range between 1 to 23. So as we can see, the majority of treatment attempts were unable to achieve adequate dose and duration which is representative of what happens in the real world clinical practice.  References:O'Reardon, J. P., H. B. Solvason, et al. (2007). "Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial." Biol Psychiatry62(11): 1208-1216.
  • So lets take a look at the key outcome measure of these 164 indicated patients in the Neuronetics-sponsored Randomized Controlled trial. We used the Montgomery Asberg Depression Rating Scale change score from baseline as the primary outcome measure. You can see that in this difficult to treat population, after six weeks of treatment there was a clear separation between the sham-treated group, represented here in gray and the active TMS group, represented here in blue, with statistically-significant separation occurring as early as Week 2. In a controlled trial, patients treated with active NeuroStar TMS Therapy received greater than 3 times the improvement in depressive symptoms compared to placebo at four weeks (-7.1 vs -2.1, P=0.0006). So this shows us that there is clear evidence that active NeuroStar TMS Therapy is an effective antidepressant when compared to sham treatment. References:Demitrack, MA , Thase, ME,. (2009) Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharm Bulletin42(2):5-38
  • Let’s examine the data from the randomized controlled trial in a format that clinicians more typically utilize in daily practice and patients more commonly understand – response and remission rates. When we review the secondary efficacy outcomes, which were response and remission rates for NeuroStar TMS Therapy vs Sham at week 4 and 6, we see rates that are 2 to 3 times better in the active group!Again, lets remember we are studying the effectiveness of TMS Therapy as a monotherapy in a group that has already failed multiple medications. Reviewing these scores (utilizing the MADRS and Hamilton Depression Rating Scale 17 and 24 question scale), we see a clear separation between the active and sham group – between 2 and 3 times better!
  • As I mentioned earlier, patients that did not improve in the Randomized Controlled Trial, had the option (after 4 weeks) to enter into the Open-Label extension study. Utilizing the Hamilton 24 Question Depression Rating Scale, we see significant response and remission rates demonstrated in the group transitioning from Sham treatment to Active NeuroStar TMS Therapy. Of the group receiving Sham treatment in the previous Randomized Controlled Study, 53.3% achieved response and 32.6% achieved remission at the end of 6 weeks of active NeuroStar TMS Therapy. Remember that response is 50% or greater improvement in depression symptoms and remission is a complete resolution of symptoms.This is important for several reasons. First, it shows that NeuroStar TMS consistently demonstrates significant response and remission rates in a difficult to treat population. And two, an open-label study like this more closely mirrors what can occur in clinical practice – 1 in 2 patients will respond and 1 in 3 patients will remit after receiving NeuroStar TMS Therapy for 6 weeks.
  • This slide shows an analysis of effect size for NeuroStar TMS Therapy compared to antidepressant medication. Effect size is one way to compare treatment effects when direct comparative trials are not available. An effect size of zero would mean the two ranges (the sham and active group) overlap completely,with their averages being the same. The larger the effect size the greater the improvement for active treatment group compared to the control group.This graph on the right shows the overall standardized effect size from trials of 12 marketed antidepressant medications. The reported effect size is shown to be 0.31 for the HAM-D17 rating scale.The left graph shows the randomized controlled trial for the NeuroStar System. The value of effect size on the HAM-D17 is shown at 0.52. As demonstrated, the effect size of NeuroStar TMS Therapy compares well to that of antidepressant medication.
  • So now that we’ve reviewed efficacy and safety data from the NeuroStar Clinical Development Program, let’s discuss a subsequent trial - the second-largest, randomized, sham-controlled clinical trial examining the safety and efficacy of NeuroStar TMS in major depression. the Optimization of TMS or ‘OPT-TMS’ Study. This independent study reinforces the efficacy and safety of TMS and is very important study for several reasons: 1) It was funded by the National Institute of Mental Health and is independent of industry. The trial did use the NeuroStar System2) It employed a similar rigorous randomized controlled trial design involving the treatment of 190 patients at 4 premier academic sites 3) It achieved a primary outcome measure (remission at 3 weeks) of 15% active TMS vs. 4% sham treatment – this is a remission rate almost 4 times greater in the active group then those receiving sham treatment, again studying a difficult to treat patient population Over, the trial design and patient population for this independent randomized controlled trial was similar to the Neuronetics study. And The main results of this study confirmed the observations of our trial, showing a statistically and clinically significant primary outcome measure. References:George, MS, Lisanby, SH, Avery, D, McDonald, WM, Durkalski, V, Pavlicova, M, Anderson, B, Nahas, Z, Bulow, P, Zarkowski, P, Holtzheimer, P, Schwartz, T, Sackeim, HA. (2010) Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Archives of General Psychiatry67(5):507-516
  • This was a naturalistic study to demonstrate acute efficacy Outcomes in Real-World Clinical Practice.The goal of this study was to define real-world outcomes associated with NeuroStar TMS Therapy across a broad spectrum of patients and practitioners. This was not a monotherapy trial so patients could be on medication.This study involved 307 unipolar non-psychotic major depressive disorder patients enrolled within the acute phase. These patients were treated across 42 sites, comprised of both institutions and private practices with the vast majority being private practices. The acute phase of the study has concluded with the long-term phase wrapping up in October. Patients enrolled received a full course of acute treatment of NeuroStar TMS Therapy as determined by their treating psychiatrist. Following acute treatment, patient outcomes were measured and followed for twelve months. The patient treatments during the follow-up period consisted of clinical care as usual.References:Neuronetics, Inc., data on file.
  • Patients within the studied population had significant depression. Lets look at some of the characteristics of the 307 patients studied:  About two thirds were women The average age was about 49 years old For most patients (over 90%), this was a recurrent course of depressionTwo important characteristics which stand out is that one, almost half of all patients had been hospitalized at some point for their depression. Two, on average, patients had received 2.5 antidepressant treatments of adequate dose and duration in the current episode without receiving clinical benefit from these treatments. Finally, on average, the course of TMS treatment spanned about 5 to 6 weeks, with the average number of TMS sessions totaling 28. References:Carpenter, Depression and Anxiety, 2012
  • This slide shows the outcome from baseline to end of acute treatment on the clinician rating scale - CGI-Severity of Illness scale, a global illness outcome scale of disease severity rated by the psychiatrist. The distribution of scores on this scale are shown at baseline, prior to NeuroStar TMS treatment, and then at the conclusion of the acute treatment course. The distribution of scores in terms of illness severity are shown in a three-tiered grouping for each scale.For the CGI-Severity of Illness scale, the category of Markedly Ill or worse reflects either a score of 5 (markedly ill), 6 (severely ill) or 7 (among the most extremely ill patients). The category of Moderately ill reflects those patients rated as 4 (moderately ill), and the Mildly ill or better category reflects those patients rated as either a score of 3 (mildly ill), 2 (borderline mentally ill), or 1 (normal, not at all ill).With these illness severity groupings, it can be seen that from the clinician’s perspective, the majority of patients at baseline were seen as markedly ill or worse (nearly three quarters of the patients were rated at this severity level), while by the end of about 5-6 weeks of acute treatment with the NeuroStar device, more than half of patients had reached a substantial improvement at a level rated as only mildly ill or no symptoms. On this scale, 58% of patients were rated by the clinicians in this category. References:1. Carpenter LL, et al. (2012).  Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice.  Depress Anxiety 29(7):587–596.
  • The previous slide demonstrated outcomes on the clinical rated scale – The CGI-Severity of Illness scale. This slide shows the outcome from baseline to end of acute treatment on a nine-item depression scale rated by the patient, the PHQ-9.The distribution of scores on these scales are shown at baseline, prior to NeuroStar TMS treatment, and then at the conclusion of the acute treatment course. The distribution of scores in terms of illness severity is shown in a three-tiered grouping for each scale.For the PHQ-9, the category of Markedly Ill or worse reflects a total score of 15 or more (moderately severe or severe depression). The category of Moderately ill reflects those patients rated as a total score between 10 and 15 (moderate depression), and the Mildly ill or better category reflects those patients rated as a score of less than 10 (mild depression or no depression).With these illness severity groupings, it can also be seen from the patient’s perspective, the majority of patients at baseline were seen as markedly ill or worse (nearly three quarters of the patients were rated at this severity level), while by the end of about 5-6 weeks of acute treatment with the NeuroStar device, more than half of patients had reached a substantial improvement at a level rated as only mildly ill or no symptoms. On the PHQ-9 scale, 56.4% of patient rated themselves at this level of improvement. References:1. Carpenter LL, et al. (2012).  Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice.  Depress Anxiety 29(7):587–596.
  • The Outcomes studied used the CGI-Severity of Illness and the PHQ-9 rating scales. Patient response and remission levels were tracked and as you can see many patients achieved this level of wellness at the end of acute treatment with the NeuroStar TMS system.On the left, we see that 37.1% of patients are rated by the clinician as having remitted using the CGI-S (an endpoint score of 1 or 2 on this scale). And more than half, 58% are shown to respond. Similarly, on the PHQ-9 scale, 28.7% of patient self-report a score of less than 5 which defines remission. This number represents about half o the total group of responding patients – 56.4% overall. So again we see there is a consistent response and remission rate demonstrated across all open-label trials. As we previously reviewed, the remission rate, which is the overall goal of depression treatment, in the Neuronetics open-label trial was 32.6%.References:1. Carpenter LL, et al. (2012).  Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice.  Depress Anxiety 29(7):587–596.
  • The Outcomes studied used the CGI-Severity of Illness and the PHQ-9 rating scales. Patient response and remission levels were tracked and as you can see many patients achieved this level of wellness at the end of acute treatment with the NeuroStar TMS system.On the left, we see that 37.1% of patients are rated by the clinician as having remitted using the CGI-S (an endpoint score of 1 or 2 on this scale). And more than half, 58% are shown to respond. Similarly, on the PHQ-9 scale, 28.7% of patient self-report a score of less than 5 which defines remission. This number represents about half o the total group of responding patients – 56.4% overall. So again we see there is a consistent response and remission rate demonstrated across all open-label trials. As we previously reviewed, the remission rate, which is the overall goal of depression treatment, in the Neuronetics open-label trial was 32.6%.References:1. Carpenter LL, et al. (2012).  Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice.  Depress Anxiety 29(7):587–596.
  • The Outcomes studied used the CGI-Severity of Illness and the PHQ-9 rating scales. Patient response and remission levels were tracked and as you can see many patients achieved this level of wellness at the end of acute treatment with the NeuroStar TMS system.On the left, we see that 37.1% of patients are rated by the clinician as having remitted using the CGI-S (an endpoint score of 1 or 2 on this scale). And more than half, 58% are shown to respond. Similarly, on the PHQ-9 scale, 28.7% of patient self-report a score of less than 5 which defines remission. This number represents about half o the total group of responding patients – 56.4% overall. So again we see there is a consistent response and remission rate demonstrated across all open-label trials. As we previously reviewed, the remission rate, which is the overall goal of depression treatment, in the Neuronetics open-label trial was 32.6%.References:1. Carpenter LL, et al. (2012).  Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice.  Depress Anxiety 29(7):587–596.
  • In summary, the data demonstrating the efficacy of NeuroStar TMS Therapy has been established in 6 studies with over 800 patients. This includes: Two, large, rigourous multisite randomized, sham-controlled clinical trials, both of which have shown clinically significant antidepressant effects of TMS. One of which was NIMH sponsored, independent of industry Two open-label extension studies demonstrating consistent response and remission rates One open-label long term follow-up study demonstrating durability One multisite, real world observational study which replicated results seen in previous studies. Overall, NeuroStar TMS Therapy shows consistent outcomes that over 1 in 2 patients achieve clinical response to treatment, and 1 in 3 reach full remission. Beyond its efficacy profiles, NeuroStar TMS Therapy has an excellent safety profile with a high level of treatment adherence and a less than 5% discontinuation rate due to adverse events.  References:Neuronetics, Inc. data on file.
  • Finally, this is a treatment that is now well established far beyond clinical trials. Beyond the AHRQ report which we’ve already discussed, this treatment option was included in the revised 2010 American Psychiatric Association Best Practices Treatment Guideline for Depression. There are 3 CPT 1 codes established for TMS as well as several coverage policies in place. There are over 460 NeuroStar Systems installed through this US, which have been used to perform over 270,000 treatments for over 11,000 patients.
  • This is the Indication for Use of the NeuroStar TMS Therapy System as provided in the product labeling and based on the randomized, controlled studies just presented.The NeuroStar System is indicated for use in the treatment of adult patients with 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. The average number of overall treatment attempts (adequate and inadequate dose and duration) was 4, with a range across the study population from 1 to as many as 23 treatment attempts. As stated earlier, the “one prior medication” stated within the indication refers to a treatment attempt where the medication was used at adequate dose and duration, which is generally defined as the minimum labeled dose for at least a period of 4 weeks. We know that, on average, for every one treatment attempt that meets these criteria, about four treatments have been attempted in the current episode, and that 3 of them were inadequate in dose or duration. References:Demitrack, MA , Thase, ME,. (2009) Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharm Bulletin42(2): 5-38NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA; 2008.
  • As I noted previously, TMS is now incorporated as an accepted treatment option for patients who have failed to benefit from initial antidepressant medication treatment for their illness. This is reflected in a growing body of published consensus. I mentioned earlier the recent publication of the APA Practice Guidelines, and you can read the quote from the Executive Summary of that document on this slide. Several other organizations have also acknowledged the scientific evidence for the safety and efficacy of TMS, including the World Federation of Societies for Biological Psychiatry (2009), and the Canadian Network for Mood and Anxiety Treatments (CANMAT, 2009). References:American Psychiatric Association (2010) (eds: Gelenberg, AJ, Freeman, MP, Markowitz, JC, Rosenbaum, JF, Thase, ME, Trivedi, MH, Van Rhoads, RS). Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd Edition.Kennedy, SH, Milev, R, Giacobbe, P, Ramasubbu, R, Lam, RW, Parikh, SV, Patten, SB, Ravindran, AV. (2009) Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Aff Disorders 117:S44-S53.Schlaepfer, TE, George, MS, Mayberg, H. (2009) WFSBP Guidelines on Brain Stimulation Treatments in Psychiatry. World J Biol Psychiatry Aug 26:1-7.
  • NeuroStar TMS Therapy is also represented in some of the top Psychiatric Hospitals as recognized by the 2012 US News and World Report.
  • Earlier, we watched two patients recount their struggles with depression. Let’s revisit these same patients as they describe how NeuroStar TMS Therapy improved their lives.
  • In summary, I’ve shown you that NeuroStar TMS Therapy is an effective, proven treatment for major depression when initial drug treatment fails. It is now included the APA Practice Guidelines for the treatment of depression. And it is a valuable treatment for patients who want to reduce their medications and their side effect burden.
  • Of course many patients ultimately decide to pay cash for TMS therapy. In order to make this available to as many patients as possible, we offer a variety of patient financing options through third-party lenders. You can offer these options to your patients, giving them flexible TMS Therapy financing options to meet their individual needs.
  • Neuronetics works diligently to get the story out about the availability and the importance of NeuroStar TMS Therapy, and here you see just a handful of clips ranging from Time Magazine to US News and World Report that represents the kind of stories that we’ve been able to produce.You can also log on to the Recent Press Coverage section of our Website (the address is shown here) where you can see a whole host of local TV news stories that have occurred as a result of a productive joint effort between Neuronetics and local providers.
  • NeuroStar has been reported throughout TV news outlets, magazines and other media. It’s getting tremendous press coverage throughout the country given its safety and effectiveness in treating a very widespread condition such as major depression.
  • We understand that reimbursement is a complex process so Neuronetics offers dedicated professionals to assist with the reimbursement process at all levels. We offer you and your office a Reimbursement Manager who will be your personal liaison to educate on fee planning, coding, billing, and the prior approval and appeals processes. In addition, it you would like to speak with this person to discuss Neuronetics Reimbursement Support Services for TMS in general, I can arrange that for you.The Health Care Policy Team is solely dedicated to obtaining coverage policy and case consideration agreements with the payers. Payers prefer to work with physicians so we encourage partnership with TMS physicians and work directly with you to obtain insurance coverage in your area.NeuroStar Reimbursement Support is our Reimbursement Support Hotline available to you and your patient s to assist with general insurance question. Your office will be introduced to a dedicated reimbursement specialist that can assist you with benefits , and to provide information regarding prior authorization and the appeals process.
  • *This slide is for informational purposes only. Final Coding and Billing decisions should be determined by the physician and/or facility. Coverage guidelines may vary according to the insurance carrier and to the patient’s specific plan. 90867: GUIDELINES (as stated in the CPT Coding Book): (Report only once per course of treatment) (Do not report 90867 in conjunction with 95928, 95929, 90868, 90869) *95928: Central motor evoked potential study (transcranial motor stimulation); upper limbs *95929: Central motor evoked potential study (transcranial motor stimulation); lower limbs - The note for these diagnostic codes was added by the AMA to make it clear that these codes cannot be billed with 90867. For the initial visit (day one of TMS Therapy) when a treatment planning session and a treatment delivery session are completed, 90867 would include both services performed on the same day. Now 90867 includes “delivery and management” whereas before it only stated planning.90867 and 90869 cannot be billed together according to the guidelines.90868:This is the code that is billed for the each session that the patient has daily.90869: GUIDELINES (as stated in the CPT Coding Book): (Do not report 90869 in conjunction with 90867, 90868) This is the 3rd code for TMS Therapy was created for those individual patient cases when re-determining the motor threshold (MT) is clinically appropriate. 90869 cannot be billed together with 90867 and 90868 according to the guidelines. Proper and thorough documentation should be done in case a payer requests notes during the claims review.
  • Neuronetics is also leading the effort to ensure widespread health insurance coverage for TMS Therapy. There is tremendous momentum with both government and commercial payers issuing coverage policies for NeuroStar TMSThroughout the country, we work very closely with interested NeuroStar providers to educate health insurers within their region about the safety and effectiveness of NeuroStar TMS Therapy.Now let’s talk about what this means for the NeuroStar provider who offers NeuroStar TMS Therapy for their patients..
  • Let’s discuss NeuroStar Reimbursement Support in further depth. The NRS provides three basic services:Benefits Investigation- Once your office submits patient information via a patient enrollment form to NRS, they will contact the payer to obtain benefit information for TMS. NRS will contact to inform you that they have received the information and that they will begin the BI Process. NRS will then provide you with that information within 4 business days. The patient can also initiate this process by working with NRS directly.Prior Authorization Assistance- NRS will inform you on patient eligibility and guidelines for prior authorization.Appeal Processes Assistance- If a patient is denied by the payer, NRS will provide general assistance on the necessary steps for appeal.
  • Lets hear from some NeuroStar providers as they discuss the value they received for the investment made in NeuroStar TMS Therapy.
  • When it comes to financing the NeuroStar system, Neuronetics offers a range of flexible options. As a provider, leasing options are available from finance groups who know and work with psychiatrists. Flexible payment structures offered by financial groups knowledgeable about the NeuroStar system means you’ll have easy monthly payments which improve your practice cash flow. So you can offer the benefits of NeuroStar TMS Therapy to your patients without the financial burden of purchasing cutting edge capital equipment.
  • For full prescribing and safety information, please visit www.neurostar.com. NeuroStar TMS Therapy is contraindicated in patients with implanted metallic devices or non-removable metallic objects in or around the head Patients treated with TMS Therapy should be monitored for symptoms of worsening depression There is a rare risk of seizure with TMS Therapy (incidence of <0.1% per acute treatment course) NeuroStar TMS Therapy has not been studied in patients who have not received benefit from initial antidepressant treatment and has not been shown to be effective in patients outside the indicated population for use NeuroStar TMS Therapy is not appropriate for all patients with depression; patients should be evaluated by their physician to determine if TMS Therapy is an appropriate treatment option NeuroStar TMS Therapy is available by prescription only
  • Thank you for your time.
  • There has been a lot of discussion lately surrounding Deep TMS and its ability to reach deeper brain structures. The Brainsway’s device uses a variation of research air-cooled coil technology, known as a Hesed coil, which is vastly different than the first to market patented solid ferromagnetic coil technology used by the NeuroStar TMS Therapy System. The Hesed Coil (also referred to as the H-Coil) uses multiple magnets to produce a diffuse magnetic field which Brainsway claims can reach deeper brain structures. Based on published literature comparing TMS coil technologies, we understand their coil does stimulate a greater volume of brain tissue and can reach depths approximately .5 cm deeper then NeuroStar TMS (Neuronetics, Data on file).
  • However, we consider their claims to be misleading, since the majority of tissue stimulated by their technology is not associated with relevant deep-brain structures (i.e. the limbic system) thought to be involved in mood regulation.
  • The patented solid ferromagnetic coil technology used by the NeuroStar TMS Therapy System allows targeted stimulation of cortical neurons in brain structures associated with mood.- Precise pulsed magnetic fields induce small electric currents in the prefrontal cortex of the brain- Local neurons depolarize which leads to activation of deep brain structures via trans-synaptic pathways- Activation of these pathways in the limbic system leads to the release of neurotransmitters - Blood flow and glucose metabolism rise in the activated regions, which is thought to result in improved moodIn reviewing the NeuroStar TMS Therapy mechanism of action, we see that targeted stimulation of local cortical neurons leads to indirect stimulation of distal networks known to be involved in mood regulation.
  • TMS Therapy at Pilsen Wellness Center

    1. 1. Advancing the Way In Treating Major Depression
    2. 2. MDD: A Large Patient Population That Is Currently Being Underserved 14 Million MOA US Adults with MDD NeuroStar SYSTEM 7.2 Million Treated 4 Million Poorly Served CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT •Inadequate response •Intolerant to side effects Kessler RC et al. JAMA. 2003;289(23):3095-3105. VALUE OF A NeuroStar OTHER 2
    3. 3. This means every 20 MDD sufferers… MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 3
    4. 4. …15 are not being adequately treated. MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 4
    5. 5. Current Drug Treatment Paradigm for Depression MOA NeuroStar SYSTEM CLINICAL DATA SSRI PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010) 5
    6. 6. Major Depression Current Treatment Landscape With each successive treatment failure, the landscape changes: MOA Efficacy, Adverse Events, and Durability Results With Each Successive Treatment Failure NeuroStar High SYSTEM Intolerance due to adverse events worsens Likelihood of longterm durability of benefit declines CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT Likelihood of benefit from the next option diminishes Low Treatment Responsive Disease Staging (# of Tx Failures) Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry Treatment Resistant VALUE OF A NeuroStar OTHER 6
    7. 7. STAR*D Study demonstrates that current treatment has limited effectiveness MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry 7
    8. 8. Likelihood of discontinuing treatment increases with each new medication attempt MOA Systemic Drug Side Effects  Weight Gain  Fatigue  Constipation  Headache/ SYSTEM Migraine  Diarrhea   Nausea Abnormal CLINICAL Ejaculation DATA  Drowsiness  Impotence  Insomnia   Decreased Libido   Nervous Anxiety  Increased Appetite  Decreased Appetite NeuroStar PRACTICE Sweating SUCCESS PROGRAM Tremor  Treatment REIMBURSEDiscontinuation MENT Side Effects   WeaknessVALUE OF A NeuroStar Dry Mouth  Dizziness OTHER 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) 8
    9. 9. The Burden of Major Depression MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 9 9
    10. 10. A Major Burden for Society Today: Top 10 Causes of Disability 1. 2. Lower Respiratory Infections Diarrheal Diseases 3. UNIPOLAR MAJOR DEPRESSION 4. 5. 6. 7. 8. 9. 10. Ischemic Heart Disease HIV/AIDS Cerebrovascular Disease Premature Birth Birth Trauma Road Traffic Accidents Neonatal Infections MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER The World Health Organization. The World Health Report 2004: Changing History, Annex Table 3: Burden of disease in DALYs by cause. Geneva: WHO, 2004. 10
    11. 11. By 2030… Top 10 Causes of Disability 1. UNIPOLAR MAJOR DEPRESSION 2. 3. 4. 5. Ischemic Heart Disease Road Traffic Accidents Cerebrovascular Disease Chronic Obstructive Pulmonary Disease 6. Lower Respiratory Infections 7. War 8. HIV/AIDS 9. Diabetes 10. Neonatal Infections MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER The World Health Organization. The World Health Report 2004: Changing History, Annex Table 3: Burden of disease in DALYs by cause. Geneva: WHO, 2004. 11
    12. 12. Consumers want alternatives in overcoming Depression… MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 12
    13. 13. NeuroStar TMS Therapy: An EffectiveTreatment for Depression • A complete clinical system using a highly focused pulsed magnetic field to stimulate NeuroStar nerve cells in the area of the brain that controls mood. MOA SYSTEM CLINICAL DATA • The first TMS system cleared by the US Food and Drug Administration (FDA) for the treatment of patients with major depression when initial antidepressant medication fails. PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 13
    14. 14. NeuroStar TMS Session MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 14
    15. 15. UNMET NEEDS NeuroStar SYSTEM Mechanism of Action CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 15
    16. 16. Major Depressive Disorder UNMET NEEDS prefrontal cortex anterior cingulate cortex striatum NeuroStar SYSTEM hypothalamus thalamus amygdala brainstem neurotransmitter centers CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT hippocampus VALUE OF A NeuroStar OTHER 16
    17. 17. Major Depressive Disorder UNMET NEEDS prefrontal cortex anterior cingulate cortex striatum NeuroStar hypothalamus HIGH thalamus Neural Activity LOW amygdala brainstem neurotransmitter centers hippocampus SYSTEM In MDD, some areas of the brain are hypoactive and others are hyperactive. CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 17
    18. 18. Major Depressive Disorder Circuits and Neurotransmitters UNMET NEEDS NeuroStar monoamine neurotransmitter projections Regions implicated in MDD are connected to the brainstem via monoaminergic circuits When there is an appropriate amount of monoamine neurotransmitter activity, neuronal activity throughout the brain functions normally. SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Monoamine Neurotransmitters Serotonin (5-HT) Dopamine (DA) Norepinephrine (NE) OTHER 18
    19. 19. Major Depressive Disorder Circuits and Neurotransmitters UNMET NEEDS concentration pleasure/ interests psychomotor fatigue (physical) pleasure/interests psychomotor fatigue (mental) sleep appetite guilt suicidality worthlessness • Monoamine dysfunction is linked to MDD • Malfunctioning circuits lead to specific symptoms mood guilt suicidality worthlessness mood Monoamine Neurotransmitters Serotonin (5-HT) NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Dopamine (DA) Norepinephrine (NE) OTHER
    20. 20. Chemical Antidepressants Therapeutic Effects such as : UNMET NEEDS Antidepressant increased concentration NeuroStar SYSTEM CLINICAL DATA improved mood reduced feelings of guilt, suicidality, and worthlessness PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 20
    21. 21. Chemical Antidepressants Antidepressant UNMET NEEDS Side Effects such as: blurred vision agitation insomnia dry mouth nausea GI distress sexual dysfunction weight gain insomnia fatigue blood pressure changes NeuroStar SYSTEM CLINICAL DATA weight gain PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 21
    22. 22. NeuroStar Directly Depolarizes Cortical Neurons UNMET NEEDS Depolarization leads to action potentials in local neurons and thereby releases neurotransmitters Neuron Neurons are “electrochemical cells” and respond to either electrical or chemical stimulation Precise pulsed magnetic fields from NeuroStar: • induce a local electric current in the cortex which depolarizes neurons • elicit action potentials • cause the release of chemical neurotransmitters NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 22
    23. 23. NeuroStar Releases Neurotransmitters in the Brain These effects Depolarization of neurons in the DLPFC causes local neurotransmitter release demonstrate improvements in depressive symptoms UNMET NEEDS Dorsolateral prefrontal cortex NeuroStar SYSTEM Cingulate cortex CLINICAL DATA Kito (2008) J Neuropsychiatry Clin Neurosci PRACTICE SUCCESS PROGRAM REIMBURSEMENT Depolarization of pyramidal neurons in the DLPFC causes neurotransmitter release in deeper brain neurons Activation of deeper brain neurons then exerts secondary effects on remaining portions of targeted mood circuits VALUE OF A NeuroStar OTHER 23
    24. 24. Mechanism of Action Summary UNMET NEEDS NeuroStar TMS Therapy… • Specifically targets the underlying brain circuits involved in NeuroStar mood regulation SYSTEM • Directly depolarizes cortical neurons and modulates CLINICAL neurotransmitter release in the brain DATA • Effects involve both the local and deep neural circuits in the PRACTICE SUCCESS brain PROGRAM • Accomplishes these effects without unwanted systemic adverse REIMBURSEeffects MENT VALUE OF A NeuroStar OTHER 24
    25. 25. TMS Therapy is not ECT UNMET NEEDS NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 25
    26. 26. UNMET NEEDS The NeuroStar TMS Therapy System MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 26
    27. 27. NeuroStar TMS in Clinical Practice UNMET NEEDS • Non-invasive • No anesthesia or sedation • Outpatient procedure easily performed in psychiatrists‟ offices • 37-minute daily procedure (3000 pulses) • 4-6 week treatment course • Antidepressant medication monotherapy may be used for maintenance MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 27
    28. 28. NeuroStar TMS Therapy System UNMET NEEDS MOA User Interface Treatment Coil CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT Mobile Console VALUE OF A NeuroStar OTHER 28
    29. 29. Accurate, Repeatable Positioning Patented 3D Coil Positioning System Accurately uses external cranial landmarks for precise, targeted repeatable stimulation • Integrated laser facilitates accurate alignment of patient‟s head within head support • Maintains proper patient alignment throughout treatment UNMET NEEDS MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 29
    30. 30. Designed for Cortical Neuron Stimulation Patented Precision Pulse TMS™ Technology • • • Proprietary coil design increases efficiency and reduces heating to permit high patient throughput Focuses stimulation to the intended target tissue to maximize safety and efficacy Electromagnetic pulse duration designed to stimulate cortical neurons (<200 microseconds) UNMET NEEDS MOA < NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 30
    31. 31. SenStar® Key Link to Consistent Treatment UNMET NEEDS SenStar Treatment Link MOA MAGNETIC FIELD DETECTOR Verifies intensity of the magnetic field before every treatment SENSORY GUARD Reduces magnetic field strength at the scalp CONTACT SENSOR Constantly monitors proper contact to ensure maximum therapy SMART CHIP Signal processor remembers unique SenStar ID and monitors treatment status CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar HYGIENE BARRIER OTHER Layered SenStar Illustration 31
    32. 32. SenStar Real Time Treatment Monitoring UNMET NEEDS SenStar Treatment Link MOA Attached to coil, continuously communicates with the NeuroStar System, allowing the operator to: • Verify correct magnetic field strength for each treatment • Monitor coil/patient contact to ensure consistent stimulation of the cortex • Ensure proper coil to head alignment CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 32
    33. 33. Intuitive User Interface UNMET NEEDS NeuroStar TMS Therapy System Software MOA • Complete software system easily guides operator step-by-step through entire treatment workflow CLINICAL DATA • Controls therapeutic settings for safe and effective treatment PRACTICE SUCCESS PROGRAM • Automatically stores and recalls individual patient data for subsequent treatments REIMBURSEMENT • Aids compliance with NINDS Safety Guidelines* VALUE OF A NeuroStar OTHER *Wassermann. Electroencephalography and clinical Neurophysiology, 1996. 33
    34. 34. TMS TrakStar™ Simplifies Practice Management UNMET NEEDS TMS TrakStar™ Practice Data Management System • Centralized patient database for single or multiple NeuroStar systems • Tracks NeuroStar treatment history • Tracks clinical outcomes • Produces reports for patient records, reimbursement claims and communication to referring physicians MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Sample Outcomes Tracking Report OTHER 34
    35. 35. TMS TrakStar™ Stores Data for Single or Multiple Systems UNMET NEEDS MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 35
    36. 36. Who Is Neuronetics? UNMET NEEDS • Founded in 2003 • Highly experienced management and clinical team • 21 TMS patents • Significant support from top tier medical technology investors MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 36
    37. 37. Who Is Neuronetics? UNMET NEEDS • Leader in TMS Therapy innovation, quality, clinical research, product development and support • Pioneered TMS Therapy and made it a clinical reality in multiple practice settings • Solely focused on the long term success of physicians and the health of their patients MOA CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 37
    38. 38. UNMET NEEDS MOA NeuroStar SYSTEM Clinical Data PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER
    39. 39. Agency for Healthcare Research and Quality Confirms Evidence Base for Efficacy of TMS UNMET NEEDS • Independent, Peer-reviewed • 15 TMS clinical trials involving nearly 500 patients • Average HAM-D decrease in depressive symptoms >5 points vs. sham control MOA NeuroStar SYSTEM • Meets clinical significance threshold of 3 points on the HAM-D scale • Response rate with active TMS was >3x higher than sham treatment • Remission rate with active TMS was >6x higher than sham treatment “High strength of evidence” for efficacy from well-controlled RCTs PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Agency for Healthcare Research and Quality: Comparative Effectiveness Report on Non-Pharmacologic Treatments for Depression , October 2011 39
    40. 40. A Rigorous Clinical Program to Prove Safety and Efficacy UNMET NEEDS NeuroStar Clinical Development Program MOA Acute Efficacy & Safety Study (Double Blind, Sham Controlled) Improved Durability of Effect Study Not Improved Open-Label Extension Study NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM Improved REIMBURSEMENT VALUE OF A NeuroStar These studies form the basis for FDA-clearance of the NeuroStar TMS Therapy System O‟Reardon, et al. (2007), Biological Psychiatry; Avery, et al. (2007), J Clin Psychiatry; Janicak, et al. (2010), Brain Stimulation OTHER 40
    41. 41. A Randomized Controlled Trial Conducted In a “Difficult to Treat” Population UNMET NEEDS TMS monotherapy trial with wash-out period • Primary diagnosis: DSM-IV Major Depressive Disorder • Unipolar type, non-psychotic • Moderate to severe symptoms at baseline MOA NeuroStar SYSTEM Indicated patient population (164) had extensive prior antidepressant drug exposure • Average number of antidepressant medication trials in current episode = 4 (range: 1 to 23 attempts) • Majority of treatment attempts were unable to achieve adequate dose and duration of treatment due to intolerance • Indicated patients had failed to achieve satisfactory benefit from one antidepressant medication at an adequate dose and duration in the current episode PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER O‟Reardon JP, et al. (2007). Biol Psychiatry 62(11):1208-1216.; Demitrack MA, Thase ME (2009). Psychopharmacol Bull 42(2):5-38. 41
    42. 42. There is evidence between Clear Separation Active and Sham TreatmentOutcome Measure – Randomized Controlled Trial Key UNMET NEEDS MADRS Change Score MOA NeuroStar SYSTEM Greater Than 3 Times Reduction in Depressive Symptoms at Week 4 PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER LOCF Analysis of intent-to-treat population Demitrack and Thase (2009), Psychopharm Bulletin 42
    43. 43. Response and Remission Rates 2 to 3 Times Better – Active vs. Sham UNMET NEEDS Randomized Controlled Trial – Secondary Efficacy Outcomes Response and Remission Rates for NeuroStar TMS Therapy vs. Sham at 6 Weeks MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Response = ≥50% improvement at end point compared to baseline score Remission = HAMD24 total score of <11 = P <0.05 OTHER * 43 Demitrack MA, Thase ME (2009). Psychopharmacol Bull 42(2):5-38.
    44. 44. Significant Response and Remission Rates UNMET NEEDS HAMD-24 Response and Remission Rates in the Group Transitioning from Sham to Active Treatment MOA NeuroStar 60 SYSTEM 53.3 50 40 37.2 32.6 30 23.3 18.6 20 10 PRACTICE SUCCESS PROGRAM REIMBURSEMENT 7.0 0 Week 2 Week 4 Remission Rate Week 6 VALUE OF A NeuroStar Response Rate OTHER 44 Demitrack MA, Thase ME (2009). Psychopharmacol Bull 42(2):5-38.
    45. 45. A Proven Safety and Patient Tolerability Profile UNMET NEEDS Less than 5% discontinuation rate due to adverse events MOA Most common adverse event related to TMS is localized pain or discomfort at or near the treatment area during active TMS NeuroStar SYSTEM • No systemic side effects • No adverse effect on cognition Post marketing experience confirms a rare risk of seizure with TMS treatment • No seizures reported during NeuroStar clinical studies (10,000 treatments) • 0.003% per treatment, <0.1% per patient • Almost 250,000 treatments to date in post-marketing experience PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Long-term safety demonstrated in 6 months follow-up OTHER Janicak, et al. J Clin Psychiatry, 2008; Janicak, et al. Brain Stimulation, 2010. 46
    46. 46. Independent Study Reinforces Efficacy Optimization of TMS („OPT-TMS‟) Study UNMET NEEDS MOA 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 NeuroStar SYSTEM • National Institute of Mental Health (NIMH) sponsored – Independent of industry • Rigorous Randomized Controlled Trial – 190 patients treated at 4 premier academic sites • Primary outcome measure: Percent Remission at 3 weeks PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar ‒ Active 15% vs. Sham 4% (P = 0.015) George, Arch Gen Psychiatry, 2010 OTHER 47
    47. 47. UNMET NEEDS NeuroStar TMS Therapy: Real World Outcomes MOA NeuroStar SYSTEM Treatment Utilization and Outcomes Study PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER
    48. 48. Naturalistic Study Demonstrates Acute Efficacy Outcomes in Real-World Clinical Practice UNMET NEEDS • Study goal was to define real world outcomes associated with NeuroStar TMS Therapy across a broad spectrum of patients and practitioners MOA • Examine acute phase response and one year patient outcomes • Patient Population & Trial Sites NeuroStar SYSTEM • 307 evaluable unipolar, non-psychotic MDD patients in acute phase • 42 sites comprised of institutions and private practice • Study Design Phases • Acute phase (treatment course driven by patient clinical response) • Long-term outcomes at 3, 6, 9 and 12 months PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Carpenter, Depression and Anxiety, 2012 49
    49. 49. Patients in this study diagnosed with Major Depression UNMET NEEDS Patient and Treatment Characteristics N (%) Female 205 (66.8) MOA Age in years, mean (SD) 48.6 (14.2) Disease and Treatment History N(%) - Recurrent Major Depression 285 (92.8) 46 (15.0) NeuroStar SYSTEM - Comorbid Anxiety Disorder Psychiatric Treatment History N(%) - History of Inpatient Hospitalization - History of ECT Treatment Prior Antidepressant Medication Treatment mean (SD) 133 (43.3) 15 (4.9) 2.5 (2.3) - Average Number of Adequate Treatments in Current Episode Mean (SD) Number of TMS Sessions During Acute Treatment 28 (10.1) PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Carpenter, Depression and Anxiety, 2012 50
    50. 50. Comparison of End of Acute Treatment Clinical Status: Clinician Assessed Outcomes UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar LOCF Analysis of intent-to-treat population Carpenter (2012), Depression and Anxiety OTHER 51
    51. 51. Comparison of End of Acute Treatment Clinical Status: Patient-Assessed Outcomes UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar LOCF Analysis of intent-to-treat population Carpenter (2012), Depression and Anxiety OTHER 52
    52. 52. Consistent Response & Remission Rates in a Difficult to Treat Population at end of Acute Phase UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar LOCF Analysis of intent-to-treat population OTHER 53 Carpenter (2012), Depression and Anxiety
    53. 53. Patient Disposition in Outcomes Study Through 1 Year Follow Up UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 54
    54. 54. Long Term Phase Results at 12 Months UNMET NEEDS Outcomes measured for one year following end of acute treatment • Physician directed standard of care • 36.2% of patients received TMS reintroduction • Average number of TMS treatment days equals 16 MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Long term durability of effect has not been established in a controlled trial LOCF Analysis; Neuronetics, Data on file, NCT 00104611 OTHER 55
    55. 55. Largest Clinical Data Set of Any TMS Therapy in Depression Six studies completed with 800 patients UNMET NEEDS • Two multisite, randomized controlled trials demonstrate clinically significant antidepressant effect of TMS • Two open-label extension studies demonstrate consistent results MOA • One prospective, naturalistic study confirms results in real-world practice • One open-label long term follow-up demonstrates safety NeuroStar TMS Therapy consistently demonstrates significant response and remission rates in a difficult to treat population: 1 in 2 patients respond 1 in 3 patients achieved complete remission of symptoms Avoids many of the systemic side effects typically associated with antidepressant medications Excellent safety profile and treatment adherence with less than 5% discontinuation rate due to adverse events NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER O‟Reardon, et al. (2007) Biological Psychiatry; Demitrack & Thase. (2009) Psychopharm Bull; George, Arch Gen Psychiatry, 2010; McDonald WM, et al. (2011) Depression and Anxiety; Carpenter (2012), Depression and Anxiety; Janicak, et al. (2010) Brain Stimulation; Janicak, et al. (2008) J Clin Psychiatry. 56
    56. 56. NeuroStar TMS Therapy is an Established Therapy Beyond Clinical Trials UNMET NEEDS MOA • Independent, Peer Review analysis (AHRQ) confirms efficacy in TMS class NeuroStar SYSTEM • Included in the revised 2010 American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients With Major Depressive Disorder • Several government and commercial payers have developedPRACTICE SUCCESS coverage policies for TMS PROGRAM • Three CPT 1 codes established for TMS REIMBURSEMENT • Approximately 470+ NeuroStar Systems Installed • Over 11,000 patients safely treated with NeuroStar TMS VALUE OF A Therapy NeuroStar OTHER Agency for Healthcare Research and Quality: Comparative Effectiveness Report on Non-Pharmacologic Treatments for Depression, October 2011; Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3 rd Edition (2010) American Psychiatric Association; 57
    57. 57. NeuroStar TMS Therapy: Indication for Use 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… UNMET NEEDS MOA NeuroStar SYSTEM ” Nearly all patients received multiple inadequate treatment attempts in current episode (range: 1 to 23 attempts, avg: 4) Demitrack & Thase. (2009) Psychopharm Bull PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 58
    58. 58. TMS is Included in Practice Guidelines Following Failure of Initial Treatment UNMET NEEDS Guideline Sources MOA “…Acute phase treatment may include pharmacotherapy, depressionfocused psychotherapy, the combination of medications and psychotherapy, or other somatic therapies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or light therapy…” NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Schlaepfer, et al. World J Biol Psychiatry (2009); Kennedy, et al J Aff Disorders (2009); American Psychiatric Association (2010) 59
    59. 59. Top Psychiatry Facilities Provide NeuroStar TMS Therapy UNMET NEEDS MOA • Johns Hopkins Hospital, Baltimore, Maryland • McLean Hospital, Belmont, Massachusetts • Sheppard and Enoch Pratt Hospital, Baltimore, Maryland • Mayo Clinic, Rochester, Minnesota • UCLA, Los Angeles, California NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT Other notable hospitals and institutions include: Stanford Hospital, Alegent Health, Berenson-Allen Center for Noninvasive Brain Stimulation (Beth Israel DMC), Florida Hospital, University of Michigan, Butler Hospital/Brown University, Medical University of South Carolina, Rush University, Walter Reed, University of Florida, Loma Linda University, Boston University, University of South Florida and Southern Illinois University, VALUE OF A NeuroStar OTHER 60
    60. 60. Patient Experiences with NeuroStar UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 61
    61. 61. Best Practices Treatment Guideline for Depression Based on 2010 APA guidelines and NeuroStar TMS Therapy UNMET NEEDS MOA NeuroStar SYSTEM SSRI PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010) 62
    62. 62. Who is the NeuroStar TMS Therapy Patient? UNMET NEEDS MOA • In a recurrent episode of depression • Has had many medication attempts, yet remains NeuroStar SYSTEM symptomatic • Due to intolerance, patient has only been able to take one medication at adequate dose and duration • Considering a complex multi-drug regimen but concerned PRACTICE SUCCESS about side effects: PROGRAM • Adding another antidepressant medication REIMBURSEMENT • Stepping up to an atypical antipsychotic or patient has already failed to benefit from one VALUE OF A • Demonstrates motivation for change NeuroStar OTHER 63
    63. 63. Who is a NeuroStar TMS Therapy Patient UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 64
    64. 64. Sarah G. Age 37 UNMET NEEDS MOA NeuroStar SYSTEM Sarah G was first diagnosed with depression at age 20. This recurrent episode was precipitated by dealing with infertility. She tried an SSRI for eight weeks which worked in the past but not in this episode. She has added duloxetine and bupropion, but could not tolerate the side effects and remains symptomatic with difficulty sleeping. She is a school administrator, enjoys her job and loves the benefits of the school calendar. She really wants to get better so she and her husband can begin the adoption process and start a family. PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 65
    65. 65. George T. Age 52 UNMET NEEDS MOA NeuroStar SYSTEM George T is a computer programmer for a fast paced, high tech company. He loves his job and it makes him feel young at age 52. He has had depression for many years and good success with medications in the past. In this episode however, the drugs are just not working, even after many medication attempts, one of which was even for 8 weeks. He even tried an augmentation therapy with an atypical antipsychotic in this episode but had to stop due to weight gain and rising blood glucose levels. He has a family history of diabetes. He is highly motivated to pursue new treatment options because he wants to be in the game at the office. PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 66
    66. 66. Julie A. Age 49 UNMET NEEDS MOA NeuroStar SYSTEM Julie A is a classic middle aged mom, chasing her teenagers and worrying about her elderly parents. She is teaching her 17 yearold son to drive a car and wonders how she ever got to be age 49! She was first diagnosed with MDD in her early thirties along with generalized anxiety. In this recurrent episode, she has tried many medications but was only able to stay on one for 6 weeks at the right dose. And after all that work to stay on the medication, it just did not make her feel better. The other medications left her in a fog. Julie is motivated to get well because she wants to remain engaged with her busy family and to be there when her son passes his driver’s test. PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 67
    67. 67. NeuroStar TMS Therapy Summary NeuroStar TMS Therapy is: • An effective, proven treatment for major depression when initial drug treatment fails • Included in APA Practice Guidelines •A valuable treatment for patients with depression who want to reduce medications and their side effect burden UNMET NEEDS MOA NeuroStar SYSTEM PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar OTHER 68
    68. 68. UNMET NEEDS NeuroStar TMS Therapy Practice Success Program MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER
    69. 69. NeuroStar Practice Success Program Purpose: Accelerate integration of Neurostar TMS Therapy into a psychiatric practice utilizing a structured six stage process. UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT Through a focused six stage process, each with clear milestones, the practice is given a roadmap toward creating a successful NeuroStar TMS clinic. VALUE OF A NeuroStar OTHER 70
    70. 70. Practice Success Program Resources UNMET NEEDS •Neuronetics TMS Specialist: Assigned to the practice to drive the process •Practice resources: Physician, TMS Coordinator and practice staff align on roles and practice goals •PSP tool set: From clinical training through NeuroStar TMS consultations to tips on marketing the practice MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 71
    71. 71. Stage 1 – Planning and Installation UNMET NEEDS MOA NeuroStar SYSTEM • Your TMS Specialist will partner with you from the very beginning • You‟ll benefit from our experience as you plan the integration of your NeuroStar System into your practice CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 72
    72. 72. ® StarGuard Field Service UNMET NEEDS • “Turn-key” installation process • 24/7 hotline to our fast, responsive local service • Service representatives located throughout the U.S. • Always have access to the latest NeuroStar TMS technology for your patients MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 73
    73. 73. Stage 2 – Online and Staff Training UNMET NEEDS MOA NeuroStar SYSTEM • Build a strong foundation for your NeuroStar practice through comprehensive staff training, including training on patient finance resources • Understand best practices for identifying NeuroStar patients and developing a TMS intake process • Begin online clinical training through NeuroStar University CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 74
    74. 74. Stage 3 – Consult Training UNMET NEEDS MOA NeuroStar SYSTEM • Understand the dynamics of a NeuroStar TMS consultation • Complete review of NeuroStar patient education materials CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 75
    75. 75. Patient Education UNMET NEEDS • Wide range of patientfriendly educational materials • Provide your patients the knowledge they need to understand NeuroStar TMS Therapy • Help facilitate patient decision-making about choosing NeuroStar TMS Therapy with your guidance • Assist family members in understanding NeuroStar TMS Therapy MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 76
    76. 76. Patient Financing Options • Financing is available for NeuroStar TMS Therapy which meets the individual needs • Creates greater access to your practice, reduces the barriers to treatment • Allows consumers to bring the benefits of NeuroStar to more patients UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 77
    77. 77. Stage 4 – Clinical Training UNMET NEEDS MOA NeuroStar SYSTEM • Master the use of the NeuroStar System through our on-site Clinical Training • Performed right in your office with actual NeuroStar patients CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 78
    78. 78. NeuroStar University Clinical Training & Support UNMET NEEDS • Deliver NeuroStar TMS Therapy to your patients knowing you have received top quality NeuroStar training • Provide the highest quality clinical care to your patients • Position yourself as a leader in the emerging new field of “interventional psychiatry” MOA SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 79
    79. 79. Stage 5 – Outcome Analysis UNMET NEEDS MOA NeuroStar SYSTEM • Utilize TMS TrakStar™ Practice Data Management Software to track your outcomes as you prepare to educate your community about NeuroStar TMS Therapy • Track your outcomes for patient, referring physician and reimbursement purposes CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 80
    80. 80. Stage 6 – Increasing Awareness UNMET NEEDS MOA NeuroStar SYSTEM • Grow your NeuroStar practice by increasing TMS awareness in your community • Utilize tools and resources to educate referring physicians and reach new patients CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 81
    81. 81. Public Relations & Local Outreach UNMET NEEDS • Neuronetics works in many geographic areas to obtain local TV MOA and newspaper articles about NeuroStar TMS Therapy NeuroStar • Your NeuroStar practice can benefit from our media outreach SYSTEM and community awareness CLINICAL • Enhance your reputation in the community as a mental health DATA treatment expert REIMBURSEMENT VALUE OF A NeuroStar OTHER 82
    82. 82. NeuroStar in the News UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar http://neurostar.com/hcp/news-events-exhibits/recent-press-coverage/ OTHER 83
    83. 83. NeuroStar In The News UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 84
    84. 84. NeuroStar Practice Success Program • Neuronetics team is available to you 24/7 for service and support whenever you need it • We are your partner in helping you to build a successful NeuroStar TMS Therapy practice • We support you every step of the way with a variety of programs, services and tools UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA REIMBURSEMENT VALUE OF A NeuroStar OTHER 85
    85. 85. Reimbursement Support Services UNMET NEEDS MOA • Insurance Reimbursement is a complex process • The Neuronetics Reimbursement Team is committed to NeuroStar SYSTEM NeuroStar providing support in all areas: Reimbursement Managers PROVIDER FOCUSED SUPPORT  Provides education and individual office support  Provides general coding, billing, prior authorization and appeals assistance Health Policy Team Reimbursement Support (NRS) PAYER FACING SUPPORT Works with Payers to obtain coverage policies Works with the Provider to develop Payer Advocates SUPPORT SERVICES HOTLINE  Team who provides general reimbursement support services Conducts insurance Benefits Investigation in your office CLINICAL DATA PRACTICE SUCCESS PROGRAM VALUE OF A NeuroStar OTHER O‟Reardon JP, et al. (2007). Biol Psychiatry 62(11):1208-1216.; Demitrack MA, Thase ME (2009). Psychopharmacol Bull 42(2):5-38. 86
    86. 86. CPT Category I Codes UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM VALUE OF A NeuroStar OTHER 87
    87. 87. Progress Toward Broader Coverage UNMET NEEDS • Tremendous momentum with both commercial and government MOA payers issuing coverage policies for NeuroStar TMS Therapy NeuroStar • Neuronetics works closely with interested NeuroStar providers SYSTEM to educate insurers in their region CLINICAL DATA PRACTICE SUCCESS PROGRAM Neuronetics provides no guarantee of insurance coverage. Coverage guidelines vary with each payer according to the patient’s individual benefits plan, medical necessity and local reimbursement policies. It is the responsibility of the physician or facility to contact each carrier regarding the plan’s specific guidelines and policies. VALUE OF A NeuroStar OTHER 88
    88. 88. What does NRS do? UNMET NEEDS NeuroStar Reimbursement Services Provides These Basic Services MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM VALUE OF A NeuroStar OTHER 89
    89. 89. The Value of NeuroStar UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT OTHER 90
    90. 90. Financial Overview Specific Treatment Volumes, Revenues and Expenses Are Hypothetical Examples Only and Neuronetics Makes No Representation or Warranty That These Examples Will Apply In Your Circumstances UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT *Maximum System Capacity = 8 patients/day = 8 patients/month. **Neuronetics, Inc. does not determine the reimbursement or revenue per treatment for TMS Therapy. These ranges of revenue per treatment session are not definitive, are based on limited information, and may not apply to a particular provider or patient. Neuronetics does not endorse or advocate for any particular pricing or reimbursement structure with our customers and we are not able to advise on the reimbursement rates providers will receive in particular cases. OTHER 91
    91. 91. Flexible Financing UNMET NEEDS • Flexible equipment leasing options are NeuroStar available from financial groups who work with psychiatrists • Easy monthly payments improve cash flow • Offer the benefits of NeuroStar TMS Therapy to your patients without the financial burden of a capital equipment purchase MOA SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT OTHER 92
    92. 92. NeuroStar System Investment NeuroStar TMS Therapy System • Mobile console w/touch screen graphical user interface • Precision Pulse™ TMS Technology • Adjustable, ergonomic patient chair • 3D Coil positioning system • NeuroStar TMS Therapy System Software • TMS TrakStar™ Patient Data Management System • Installation and two-year limited warranty • Neuronetics Service & Support UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT OTHER 93
    93. 93. Summary UNMET NEEDS MOA • The NeuroStar TMS Therapy System is the first FDA-cleared non-systemic and non-invasive TMS device for the treatment ofNeuroStar SYSTEM Major Depression • NeuroStar is demonstrated to be effective and safe in the treatment of patients with MDD who had failed to benefit from initial antidepressant medication • Neuronetics partners with you and provides our complete wraparound services to successfully integrate NeuroStar TMS Therapy into your practice CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT OTHER 94
    94. 94. Prescribing and Safety Information UNMET NEEDS • Refer to www.NeuroStar.com for complete prescribing and product safety information • NeuroStar TMS Therapy is contraindicated in patients that have non-removable conductive metal in or near the head. MOA NeuroStar SYSTEM • Patients treated with TMS Therapy should be monitored for symptoms of worsening depression CLINICAL DATA • There is a rare risk of seizure with TMS Therapy (0.1% of acute treatment course) PRACTICE SUCCESS PROGRAM • NeuroStar TMS Therapy has not been studied in patients who have not received initial antidepressant treatment and has not been shown to be effective in patients outside the indicated population for use REIMBURSEMENT • NeuroStar TMS Therapy is not appropriate for all patients with depression; patients VALUE should be evaluated by their physician to determine if TMS Therapy is an appropriate OF A NeuroStar treatment option • NeuroStar TMS Therapy is available by prescription only OTHER 95
    95. 95. UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT Thank You VALUE OF A NeuroStar OTHER 96
    96. 96. UNMET NEEDS MOA NeuroStar SYSTEM Competitive Review CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar
    97. 97. Brainsway Offers Minimal Increase in Magnetic Field Depth • Brainsway device uses a variation of research air-cooled coil technology, known as a Hesed coil (H-Coil) • Vastly different than the first to market patented solid ferromagnetic coil technology used by the NeuroStar System. • Coil uses multiple magnets to produce a diffuse magnetic field • Brainsway coil stimulates greater volume of brain tissue and reaches approximately 0.5 cm deeper UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar Neuronetics, Data on File. 98
    98. 98. Brainsway Offers Minimal Increase in Magnetic Field Depth UNMET NEEDS • Brainsway‟s claim to reach deeper brain structures is misleading NeuroStar Depth Brainsway Depth • Majority of tissue stimulated is not associated with relevant deep-brain structures thought to be involved in mood regulation (i.e. the limbic system) MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar 99
    99. 99. NeuroStar TMS Therapy: A Targeted Mechanism of Action Patented solid ferromagnetic coil technology used by the NeuroStar System allows targeted stimulation of cortical neurons in brain structures associated with mood. • Precise pulsed magnetic fields induce small electric currents in the prefrontal cortex of the brain • Local neurons depolarize which leads to activation of deep brain structures via trans-synaptic pathways • Activation of these pathways in the limbic system leads to the release of neurotransmitters • Blood flow and glucose metabolism rise in the activated regions, which is thought to result in improved mood Kito (2008), Journal of Neuopsychiatry and Clinical Neuroscience. UNMET NEEDS MOA NeuroStar SYSTEM CLINICAL DATA PRACTICE SUCCESS PROGRAM REIMBURSEMENT VALUE OF A NeuroStar 100

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