Henderson depression update incl tms
•
3 j'aime•1,162 vues
Dr. Cady presented this CME program on depression and TMS (Transcranial magnetic stimulation) to the medical staff of the Community Methodist Hospital in Henderson, KY on February 8, 2012. It reviews accurate diagnosis of depression, use of new medications, cautions on drug-drug interactions, and a review of the new development of TMS in the current treatments of 21st Century psychiatry.
Recommandé
Recommandé
Contenu connexe
Tendances
Tendances (20)
Similaire à Henderson depression update incl tms
Similaire à Henderson depression update incl tms (20)
Plus de Louis Cady, MD
Plus de Louis Cady, MD (20)
Dernier
Dernier (20)
Henderson depression update incl tms
- 3. Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute Adjunct Professor – University of Southern Indiana Adjunct Clinical Lecturer – Indiana University School of Medicine Department of Psychiatry Child, Adolescent, Adult & Forensic Psychiatry – Evansville, Indiana DEPRESSION: A CME REVIEW AND UPDATE ON TREATMENTS Presented to Henderson Community Methodist Hospital – Feb 8, 2012
- 4. “ Slumber not in the tents of your fathers. The world is advancing. Advance with it.” - Giuseppe Mazzine
- 7. Comorbidity of Depression and Anxiety % Patients Disabled 3+ Days 33.7% 19.45% 16.9% 3.1% Disability Wittchen, Depress Anxiety , 2002 Percent of Patients With ≥ 1 Disability Day in Past Month GAD + MDD MDD/no GAD GAD/no MDD no GAD/no MDD
- 8. “ Drug-drug interactions” clinically relevant?!
- 9. Drug-drug interactions: chum for legal “sharks”
- 10. “ Strattera [coupled with Prozac or Paxil] has been great for our admissions. ” -Dr. William Beute, MD Pine Rest Campus Clinic Grand Rapids, MI April 21, 2004 [quoted with permission]
- 11. Cytochrome p-450 2D6 inhibition measured as % increase in “Desipramine AUC” – in vivo data Preskhorn, Alderman, et al. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J. Clin Psychopharmacol 1994;14:90-98; Escitalopram package insert - note – different source of data, but same method Critically important when combining with other Rx metabolized through 2D6 pathways
- 16. Major Depression Unmet Medical Needs
- 19. Per HDRS – 17, remission in: 15.9% on Li 24.7% on T3 Per QIDS-SR16, remission in: 13.2% on Li 24.7% for T3 * * Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry LEVEL III RESULTS:
- 20. “ Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism. ” (hunh?!) http://www.umm.edu/patiented/articles/how_serious_hypothyroidism_000038_6.htm Accessed: 9/5/2011
- 21. “ the foot soldier” “ the evil twin ” CORTISOL Se ?
- 25. STAR*D Study demonstrates that current treatment has limited effectiveness Trivedi (2006) Am J Psychiatry ; Rush (2006) Am J Psychiatry ; Fava (2006) Am J Psychiatry ; McGrath (2006) Am J Psychiatry
- 27. Best Practices Treatment Guideline for Depression Based on 2010 APA guidelines and NeuroStar TMS Therapy® indication for use. Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3 rd Edition, APA (2010) Unmet Medical Needs
- 29. The Therapeutic Trifecta of Psychiatry: Shrinking Shocking or Drugging The only three things you could do to a patient’s brain…
- 30. A quick look back in history
- 31. " The Shock Shop , Mr. McMurphy, might be said to do the work of the sleeping pill, the electric chair and the torture rack. It's a clever little procedure, simple, quick, nearly painless it happens so fast, but no one ever wants another one. Ever.”
- 33. From Michael Farraday to today
- 36. ECT vs. TMS ECT TMS Anesthesia, LOC Yes No Induction of seizure Yes No Systemic effects Anesthetic drugs, increase HR none Treatment schedule 3X/ week (8 -15 tx) Daily, M-F, six weeks (30 tx) Rapidity of onset 2 – 3 treatments 2 – 3 weeks Mechanism of action SEIZURE. Massive NT release; rise in sz threshold Reactivation of neural circuits. Precise, LOCAL release of NT’s. Side effects Memory loss, confusion Essentially none (mild HA 1 st week) Psychosocial impact can’t work Drive to and from tx’s, work improved After-effects Mild (usually transient) memory loss None. Pro-cognitive Insurance coverage Almost always Rare. Improving
- 37. TMS Targeted Effects on Local and Distant Regional Blood Flow Nahas Z et al. Brain Effects of TMS Delivered Over Pefrontal Cortex in Depressed Adults. Journal of Neuropsychiatry and Clinical Neurosciences 2001:13:459-460.
- 38. Nahas Z et al. Brain Effects of TMS Delivered Over Pefrontal Cortex in Depressed Adults. Journal of Neuropsychiatry and Clinical Neurosciences 2001:13:459-460.
- 42. O’Reardon, JP, et al. (2007) Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multi-Site Randomized Controlled Trial. Biol Psychiatry 62 :1208-1216.
- 45. Active research…
- 47. Perhaps the ability not only to acquire the confidence of the patient, but to deserve it, to see what the patient desires and needs, comes through the sixth sense we call intuition, which in turn comes from wide experience and deep sympathy for and devotion to the patient , giving to the possessor remarkable ability to achieve results. ...William J. Mayo, 1935
Notes de l'éditeur
- Giuseppe Mazzini (22 June 1805 – 10 March 1872), nicknamed "Soul of Italy,"[1] was an Italian politician, journalist and activist for the unification of Italy. His efforts helped bring about the independent and unified Italy[2] in place of the several separate states, many dominated by foreign powers, that existed until the 19th century. He also helped define the modern European movement for popular democracy in a republican state. [ citation needed ] – Source - Wikipedia
- Hello. My name is Dr._____________, and I am pleased to have the opportunity to speak with you today about the role of TMS Therapy in the treatment of patients in with major depression. In this presentation, I will cover three major areas: First, I will describe the current landscape of treatment options for major depression, with a particular focus on the concept of treatment resistance. I will also review the most recent Practice Guidelines for the Treatment of Patients with Major Depressive Disorder that have been promulgated by the American Psychiatric Association, highlighting their conclusions regarding the role of TMS in clinical practice. Second, I will describe the science behind TMS, explaining what it is and how it is thought to exert its effects as an antidepressant. I will also review the most recent clinical trial evidence for its efficacy and safety. Third and finally, I will conclude by placing this data in context by specifically describing the role of TMS in the treatment of patients with major depression who have not benefited from initial treatment with antidepressant medications. At the end of this presentation, we will have time for any questions that you may have.
- Both MDD and GAD are associated with considerable functional impairment and disability. Comorbid depression and GAD tends to result in greater levels of disability as measured by the proportion of patients who report 1 or more days of disability in a 30-day period. Patients experience diminished functioning both at work and socially, with many reporting moderate or severe social disability. Reference Wittchen HU. Generalized anxiety disorder: prevalence, burden, and cost to society. Depress Anxiety . 2002;16:162-171.
- In a flexible dose study evaluating the safety and efficacy of escitalopram in the treatment of panic disorder (with or without agoraphobia), outpatients were randomized to receive placebo, citalopram or escitalopram. There were approximately 120 patients per treatment group. Following a 2-week single-blind lead-in period, patients received 10 weeks of double-blind treatment. Treatment was initiated at a low dose (10 mg/day for citalopram and 5 mg/day for escitalopram) and then titrated after one week to 20 mg/day for citalopram and 10 mg/day for escitalopram. After week 4, dose could be increased to 40 mg/day citalopram and 20 mg/day citalopram. The Panic and Anticipatory Anxiety Scale (PAAS) and the Panic and Agoraphobia (P&A) scale were used to quantify panic attacks, anticipatory anxiety, and phobic avoidance.
- First, let ’s talk about the current landscape of treatment options for major depression.
- The current treatment reality of major depression underscores that unmet needs in treatment still exist, even more than 20 years after the availability of the first modern selective serotonin reuptake inhibitor (SSRI) antidepressant. The picture on this slide summarizes the major findings from the recently completed, NIH-funded STAR*D Study. STAR*D stands for: S equenced T reatment A lternatives to R elieve D epression. This is the largest and most definitive research we have available that underscores the inadequacies of currently available treatments. The first major observation, represented by the blue line is that with each successive treatment option that fails to produce relief, the likelihood of benefiting from the next treatment offered drops. On subsequent slides, I will show the actual data from the outcomes seen in STAR*D itself. The second major observation from STAR*D is shown by the green line , and that is that with each successive treatment attempt, tolerability becomes a significant problem. It is increasingly likely that a patient will discontinue the treatment due to intolerable adverse events, clearly presenting a major concern in clinical management of depression. Finally, represented in the orange line is the fact that as patients progress to greater stages of treatment resistance (that is, when they have failed to benefit from multiple prior treatment attempts), the likelihood that they will be able to stay well over the long term also diminishes, in other words there is an increased likelihood of long-term relapse based on how treatment resistant a patient is in their acute treatment phase. Clearly, current antidepressant treatments do not result in a fully satisfactory outcome in a large proportion of patients with major depression. References : Fava, M., A. J. Rush, et al. (2006). "A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A Star*D Report." Am J Psychiatry 163 (7): 1161-1172. McGrath, P. J., J. W. Stewart, et al. (2006). "Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1531-1541. Nierenberg, A. A., M. Fava, et al. (2006). "A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1519-1530. Rush, A. J. (2007). "STAR*D: What have we learned?" Am J Psychiatry 164 (2): 201-204. Rush, A. J., M. H. Trivedi, et al. (2006). "Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report." Am J Psychiatry 163 (11): 1905-1917. Trivedi, M. H., M. Fava, et al. (2006). "Medication Augmentation after the Failure of SSRIs for Depression." New England Journal of Medicine 354 (12): 1243-1252. Trivedi, M. H., A. J. Rush, et al. (2006). "Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D Implications for Clinical Practice." Am J Psychiatry 163 (1): 28-40
- I ’ d like to expand a bit on the problem of antidepressant treatment adherence. As indicated on the previous slide, as a patient shows increasing levels of treatment resistance, the likelihood that they will keep taking the prescribed treatment also begins to decline. In fact, the occurrence of intolerable adverse events, and discontinuation of patient adherence to the treatment regimen, can become a major challenge in clinical management when treatment resistance worsens. The iceberg image on this slide portrays the nature of the problem. Clearly, getting to a defined and effective acute treatment (the tip of the iceberg) is the goal: effective treatment with the prescribed antidepressant at an adequate dose for an adequate length of time. Unfortunately, for the majority of patients, this does not occur, and is an especially significant challenge for the patient with a treatment resistant form of depression. Below the water line, are shown some of the potential factors that can confound achieving the goal of treatment adequacy. When looked at in rigorous research studies, adequate antidepressant treatment occurs in the minority of patients. Typically, only one in every four antidepressant treatments is able to achieve the ‘’ tip of the iceberg ’’ due to lack of efficacy, intolerance and other factors as shown here An effective and, most important, a tolerable treatment option is a critical goal in the setting of treatment resistance . References : Nemeroff CB. Depress Anxiety . 1996/1997;4(4):169-181 Oquendo MA, A, et al. J Clin Psychiatry . 2003;64(7):825-833 Oquendo MA, et. al. Am J Psychiatry . 1999;156(2):190-194 Prudic J, et. al. Psychol Med . 2001;31(5):929-934. Osterberg, L, et. al., NEJM , 2009 ; 353 5): 487-497
- Let ’s take a closer look at the evidence generated in the STAR*D Study. The design of this study involved four treatment Levels. These Levels were pre-specified by expert consensus, and were intended to reflect the general approach taken in clinical practice at the time STAR*D was constructed, which was about 10 years ago. Patients treated in STAR*D were either first episode patients, or treatment-responsive patients. To get into the study, the patient could not have previously been treated with and failed to benefit from any of the options offered in either Level 1 or 2. Patients were recruited from both primary care and specialty psychiatric treatment settings in the United States. About 4,000 patients entered into this study. The first Level results showed that in response to an adequate course of treatment with an SSRI (in this study, citalopram was the option used) only about 28% of patients were able to achieve remission as measured using the 17 Item Hamilton Depression Rating Scale. At Level 2, the results are shown for those patients who were offered a switch to another antidepressant of the same or a different class (these options included sertraline, bupropion SR, or venlafaxine SR). You can already observe the drop in likelihood of remission, here at about 21% after failure of only one prior adequate antidepressant treatment. At Level 3, the switch options offered were either mirtazapine or nortriptyline, and again the remission likelihood degrades further. Finally, at Level 4, the switch option offered was the MAOI tranylcypromine. Here the likelihood of remission after failure of three prior adequate treatments was 6.9%. References : Fava, M., A. J. Rush, et al. (2006). "A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A Star*D Report." Am J Psychiatry 163 (7): 1161-1172. McGrath, P. J., J. W. Stewart, et al. (2006). "Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1531-1541. Nierenberg, A. A., M. Fava, et al. (2006). "A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1519-1530. Rush, A. J. (2007). "STAR*D: What have we learned?" Am J Psychiatry 164 (2): 201-204. Rush, A. J., M. H. Trivedi, et al. (2006). "Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report." Am J Psychiatry 163 (11): 1905-1917. Trivedi, M. H., M. Fava, et al. (2006). "Medication Augmentation after the Failure of SSRIs for Depression." New England Journal of Medicine 354 (12): 1243-1252. Trivedi, M. H., A. J. Rush, et al. (2006). "Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D Implications for Clinical Practice." Am J Psychiatry 163 (1): 28-40.
- What about antidepressant tolerability and treatment adherence? A close look at the reported results of STAR*D reveals some important findings. We have learned from the STAR*D Study, that the likelihood of a patient dropping out of treatment because of side effects rises dramatically, nearly tripling in the transition from Level 1 ( about 9% ) to Level 2 ( about 23% ). By the time a patient had failed to benefit from three prior treatment attempts, the likelihood of their discontinuing due to adverse events from the next offered antidepressant monotherapy (in this case the MAOI tranylcypromine), was quite notable: slightly greater than 41% . There are many reasons why the intolerance to treatment rises with progressive levels of treatment resistance, and a full consideration of this is beyond the scope of this presentation. In general, this finding is both a reflection of how physically uncomfortable depression is as a disease, as well as the fact that each next treatment offering in this study brought the potential for an even greater degree of uncomfortable adverse events. Shown on the right side of this diagram is a list of those adverse events reported in product labels for all contemporary antidepressant medications, including the augmentation agents such as the atypical antipsychotics. The list specifically shows those adverse events that in each product ’s labeling were observed to occur at an incidence of at least 5% in the antidepressant-treated group, and occurred at a rate at least twice as high as the incidence of that event reported in the placebo group. References : Fava, M., A. J. Rush, et al. (2006). "A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A Star*D Report." Am J Psychiatry 163 (7): 1161-1172. McGrath, P. J., J. W. Stewart, et al. (2006). "Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1531-1541. Nierenberg, A. A., M. Fava, et al. (2006). "A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report." Am J Psychiatry 163 (9): 1519-1530. Rush, A. J. (2007). "STAR*D: What have we learned?" Am J Psychiatry 164 (2): 201-204. Rush, A. J., M. H. Trivedi, et al. (2006). "Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report." Am J Psychiatry 163 (11): 1905-1917. Trivedi, M. H., M. Fava, et al. (2006). "Medication Augmentation after the Failure of SSRIs for Depression." New England Journal of Medicine 354 (12): 1243-1252. Trivedi, M. H., A. J. Rush, et al. (2006). "Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D Implications for Clinical Practice." Am J Psychiatry 163 (1): 28-40. Product Labeling for currently marketed antidepressants (Neuronetics, Inc., data on file)
- In 2010, the American Psychiatric Association updated their Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, now in its 3 rd Edition. This slide depicts the general conclusions in that document for the next treatment steps in patients who have failed initial acute phase antidepressant medication. There are several points that I would like to comment on: As I mentioned above, the APA notes the progressive sequence of steps along the bottom as the next choice for antidepressant medications. As you can see, these options include both medication switches within and across pharmacologic classes, as well as augmentation options. While these options have some scientific evidence base for their support, very few have actually withstood FDA scrutiny in large, multisite, randomized controlled trials. The few that have been studied in this manner and are approved for use in treatment resistant depression are the atypical antipsychotic medications, as augmentation agents. As is also noted in this diagram and as you are well aware, each medication trial can take up to 2 months to clearly understand its potential benefits. Finally, in many instances, ongoing treatment may involve continuation of multiple antidepressant medications. TMS is now included as an accepted treatment option for patients who have failed to benefit from first line treatment attempts. As we will discuss later in this presentation, placing TMS at this earlier stage in treatment planning is consistent with the strength of the clinical trial evidence that led to the FDA clearance of the NeuroStar TMS Therapy system device. The NeuroStar TMS system is current the only TMS device in the US which has been cleared by the FDA for use in the treatment of major depression. A treatment course of TMS, as recommended in product labeling, is usually 4 to 6 weeks in duration, and when effective, has been safely followed by a course of a single antidepressant medication. 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, 3 rd Edition.
- In the following section of my talk, I ’d like to discuss TMS in more detail. I will review its mechanism of action, and then discuss some of the most recent randomized clinical trial evidence supporting its efficacy and safety. I will also discuss recent outcomes in real-world practice settings obtained from an ongoing large, prospective outcomes study.
- The underlying rationale for the use of TMS exploits the fact that neurons are elecrochemical cells. This means that neuronal activity can be affected either chemically, via the use of drugs, or electrically, via interventions like TMS. In general, while the action of drugs may be directed at a certain neurochemical receptor or protein, they are by virtue of their method of administration anatomically diffuse, and after oral ingestion, circulate systemically throughout the body, and affect any tissue of the body that possesses that neurochemical target, whether relevant to the disease being treated or not. In contrast, TMS ’s effects 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. As a targeted treatment, where should TMS be directed in the brain? The right hand side of this figure shows several key brain regions involved in the regulation of mood. Accessible on the surface of the cortex of the brain is the dorsolateral prefrontal cortex (shown in green ). Deeper underlying structures including the anterior cingulate gyrus (shown in red ) and areas of limbic system, such as the amygdala (shown in blue ) also play important roles. The arrows connecting these different brain regions indicate that these various regions (and others) communicate with each other. As a targeted treatment, TMS ’s actions are directed at the surface areas of the left dorsolateral prefrontal cortex. TMS can then indirectly exert effects to reach these underlying deeper brain structures through these regional, trans-synaptic connections. In short, TMS exerts its effects (directly and indirectly) through targeted action on brain circuits involved in the regulation of mood. References : Pizzigalli, DA. (2011) Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response. Neuropsychopharmacology 36 :183-206.
- This slide shows a schematic example of the targeted action of a TMS coil. At a practical level, a TMS coil generates strong, MRI-strength, rapidly pulsed magnetic fields. The magnetic field remains sufficiently strong to a depth of about 2-3 centimeters into the brain as it extends away from the face of the TMS magnetic coil. This rapid magnetic pulsing in turn induces an electrical current in an adjacent electrical conductor. The target electrical conductor in the case of TMS is the surface layers of the cerebral cortex of the brain. This scientific principle is known as the ‘Law of Electromagnetic Induction’ and was formally described by the English experimenter, Michael Faraday in the late 1800’s, and is sometimes referred to as ‘Faraday’s Law’. TMS therapy is a noninvasive method of stimulating areas of the brain thought to be involved in mood regulation. References : Faraday M. In: Experimental Research in Electricity . Vol 1. London Quaritch; 1839:1-15 Barker AT. An introduction to the basic principles of magnetic nerve stimulation. J Clin Neurophysiol . 1991;8(1):26-37 Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet . 1985;11(8437):1106-1107.
- This slide shows the Indication for Use of the NeuroStar TMS Therapy System, derived from the evidence presented to the FDA and that I reviewed earlier in my presentation. As I mentioned previously, all patients in the indicated population had a diagnosis of unipolar, non-psychotic major depression, with moderate to severe symptoms at entry to the study. About a third of all patients had a concurrent secondary diagnosis of an anxiety disorder. All patients received a rigorous characterization of their antidepressant medication treatment history in the current illness episode. Most patients had received numerous medication treatment attempts, with one of these treatment attempts being administered at an adequate daily dose and for at least four weeks without clinical benefit. 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. Consistent with the data that I reviewed earlier in this presentation, about 75% of the time, these antidepressant treatment attempts were unable to achieve this minimum level of exposure adequacy (usually because of treatment intolerance, or failure to adhere to the recommended treatment regimen). References : Demitrack, MA , Thase, ME,. (2009) Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharm Bulletin 42(2) : 5-38 NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA; 2008.
- This slide shows all of these scientific principles in action in a group of patients (N=12 males) with major depression who have received a course of TMS to their left prefrontal cortex. These pictures represent images from a SPECT (single photon emission computed tomography) scan of the aggregate results in these patients, looking at the areas of the brain that showed changes in cerebral blood flow that correlated with improvement in symptom ratings, as measured by the Hamilton Depression Rating Scale. On the left of the slide are the image slices showing the left side of the brain, and the right side of the brain are on your right, as labeled. The top row of images show tranverse sections moving from lower in the brain to higher in the brain, as you read from left to right. Similarly, the bottom row of images show coronal sections through the brain moving from back to front in the head as you move from left to right. You can see the approximate position of the TMS coil on the left side of the head. The area just underneath the coil is the left dorsolateral prefrontal cortex, which is showing increased metabolic activity as a direct result of the magnetic stimulation. In other panels you can also see that the increase in metabolism reaches secondarily to reach many of the deeper brain regions important in mood regulation that I mentioned earlier. For example in the middle panel on the bottom coronal section, areas of the cingulate cortex show increased activation. References : Kito, S, Fujita, K, Koga, Y. (2008) 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 20(1) :74-80.
- The NeuroStar TMS Therapy system is the only FDA-cleared TMS device for the treatment of adult patients with major depression who have failed to benefit from initial treatment. In clinical practice, TMS Therapy is: An outpatient procedure, It is non-invasive and non-systemic in action, Shows a safety profile of few side effects, Is typically performed in an outpatient setting, without need for sedation or anesthesia, A standard treatment session is 37 minutes long, and a treatment course consists of daily (5 days per week) treatments for 4 to 6 weeks, A physician or other clinical professional is in attendance during the treatment session, which facilitates adherence with the prescribed treatment References : NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA; 2008.
- The published scientific evidence supporting the antidepressant effect of TMS is substantial, and now spans nearly twenty years of scientific research, involving more than 30 published studies, and over 2000 patients. There are twelve published meta-analyses or qualitative reviews of this research. The most recent and comprehensive of these was reported by Slotema and colleagues last year. They analyzed the results of 34 studies involving 1,383 patients. They computed an effect size of 0.55 (P < 0.001), which represents a moderate to large clinical effect of TMS in the treatment of depression. In their conclusion, they noted that “…rTMS deserves a place in the standard toolbox of psychiatric treatment methods, as it is effective for depression…and has a mild side effect profile…”. References: Slotema, CW, Blom, JD, Hoek, HW, Sommer, IEC. (2010) 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. Journal of Clinical Psychiatry 71(7) :873-84. Schutter, DJLG. (2009) Antidepressant Efficacy of High-Frequency Transcranial Magnetic Stimulation Over the Left Dorsolateral Prefrontal Cortex in Double-Blind Sham-Controlled Designs: A Meta-Analysis. Psychol Medicine , 39 :65-75.
- An overall summary of the main safety findings are shown on this slide: As I discussed earlier in reviewing its mechanism of action, TMS showed no systemic side effects, There were no adverse effects on cognition as measured by formal cognitive testing using the Mini Mental Status Examination (a measure of global cognitive function), the Buschke Selective Reminding Test (a measure of short-term memory), and the Autobiographical Memory Interview Short Form (a measure of long-term memory), The most commonly reported device-related adverse event was scalp pain or discomfort in about a third of all patients, Only about 5% of patients discontinued due to adverse events, and for the majority of patients, the device-related adverse events subsided substantially after the first week of treatment Long term safety was confirmed in a six month period of follow up after benefit from acute treatment Seizure is the major, medically significant potential safety risk of TMS. During clinical trials, no seizures were observed with the NeuroStar TMS system. Since its market introduction, seizures have been reported rarely. To date, an estimated incident risk of seizure with NeuroStar TMS Therapy is approximately 0.003% per treatment exposure, and 0.1% per patient exposure. Over 100,000 treatments and over 3,000 patients have been treated with the NeuroStar TMS Therapy system which confirms its safe use in the treatment of depression. References : Janicak, PG, O ’Reardon, JP, Sampson, SM, Husain, MM, Lisanby, SH, Rado, JT, Demitrack, MA. (2008) Transcranial Magnetic Stimulation (TMS) in the Treatment of Major Depression: A Comprehensive Summary of Safety Experience from Acute and Extended Exposure and During Reintroduction Treatment. J Clin Psychiatry 69(2) :222-232. Janicak, PG, Nahas, Z, Lisanby, SH, Sovason, HB, Sampson, SM, McDonald, WM, Marangell, LB, Rosenquist, PB, McCall, WV, Kimball, J, O ’Reardon, J, Loo, C, Husain, MH, Krystal, A, Gilmer, W, Dowd, SM, Demitrack, MA, Schatzberg, AF: (2010) Long-Term Durability of Acute Response to Transcranial Magnetic Stimulation (TMS) in the Treatment of Pharmacoresistant Major Depression. Brain Stimulation 3 :187-199.
- The only absolute contraindication to the use of TMS is the presence of non-removable magnetically-active metal in the head, near the treatment coil. Additional clinical factors should be considered in determining whether the balance of potential benefits and risks of NeuroStar TMS Therapy are appropriate for any particular patient. For example: The efficacy of NeuroStar TMS Therapy has not been established in patients with major depressive disorder who have not taken any antidepressant medications or in patients who failed to benefit from 2 or more antidepressant medications in the current episode when administered at or above minimal effective dose and duration. NeuroStar has not been evaluated in patients with psychoses or with psychiatric emergencies where a rapid clinical response is needed. Patients with major depressive disorder may experience worsening of their depression or the emergence of suicidal ideation or suicidal behavior and should be closely observed during treatment. If this occurs, consideration should be given for changing the treatment regimen. NeuroStar TMS Therapy should be used with caution in patients with implanted medical devices whether controlled by physiologic signals or not. Prior to treatment, all patients should be carefully screened for the presence of metallic objects or implants that could affect the safe use of the NeuroStar TMS Therapy System. Please refer to the NeuroStar TMS Therapy System User Manual or go to www.NeuroStar.com for complete product safety information. References : NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA; 2008.