Dr. Shakir's CTF Presentation - Depression TreatmentPresentation Transcript
Latest Advances in the Art and Science of Depression • Pharmacological Treatment • Non-Pharmacological Trans-Cranial Magnetic Stimulation; FDA approved, Non-Invasive Treatment • Silicon Valley TMS, www.siliconvalleytms.com
Neuro-Psychiatry in Transition• “From Shock Therapy and Psychoanalysis to the MAGNET(TMS) and the Highways in between
Saad A. Shakir, MD, DFAPA, FACIP andAssociates,(www.siliconvalleytms.com)(408)358-8090,firstname.lastname@example.orgIntegrated Clinical Neuro-Sciences and SiliconValley TMS,Los Gatos,Formerly Adjunct Clinical Associate ProfessorEmeritus of Psychiatry and Behavioral Medicine.Stanford University,California.
Transcranial Magnetic Stimulation (TMS) A Proven Approach The treatment coil produces MRI-strength magnetic field pulses. Magnetic field pulses pass unimpeded through the cranium for 2-3 cm. and induce a small electric current. Induced electric currents stimulate the firing of nearby neurons, causing the release of neurotransmitters and clinical effects. 4Faraday (1839) Experimental Research in Electricity. Vol 1; Barker (1991) J Clin Neurophysiol; Barker (1985) Lancet
Why Depression is so ImportantIn the 21st century depression willsurpass all other medical disordersas the number one illness in theworldW.H.O., 2001.
MDD is Disabling and an Economic Burden Disability1 Economic Burden of MDD2 US (2000) Rank* 1990 2020 (est) Lower 100 1 respiratory Ischemic heart infections disease $83.1 80 Perinatal Major 2 conditions depressive US$ Billions disorder 60 Road traffic 62% 3 HIV/AIDS accidents 40 Workplace Major Cerebro- 4 depressive vascular 7% Suicide-related disorder disease 20 Direct Medical Chronic 31% 5 Diarrheal obstructive diseases pulmonary 0 disease All Costs *Rank based on a composite measure of Disability- Adjusted Life Year (DALY) in 15-44 year olds1.Murray CJ, et al. Science. 1996;274:740-743.2.Greenberg PE, et al. J Clin Psychiatry. 2003;64:1465-1475.
AMERICAN PSYCHIATRIC ASSOCIATION1 “The goal of treatment with antidepressant medications in the acute phase is the remission of major depressive disorder symptoms.”1. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry. 2000;157(4 Suppl):1-45.
THE CANADIAN PSYCHIATRIC ASSOCIATION in conjunction with THE CANADIAN NETWORK FOR MOOD AND ANXIETY TREATMENTS1 “In clinical practice, it behooves us to adequately assess and treat depressive and anxiety disorders to remission.”1. O’Donovan C. Can J Psychiatry. 2004;49(March Suppl 1):5S-9S.
AUSTRALIAN AND NEW ZEALAND CLINICAL PRACTICE GUIDELINES1 “The aim of treatment is to achieve and maintain remission.”1. Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Depression. Aust N Z JPsychiatry. 2004;38:389-407.
WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR EUROPE1 “The goal of acute treatment should always be the complete remission of the episode and not just partial improvement.”1. Möller HJ. WHO Regional Office for Europe. Health Evidence Network report. 2005.
Challenges 1.Poor Recognition2.Underdiagnosis and misdiagnosis 3.Overutilization of healthcare resources(non-Psychiatric)
1.Poor Recognition Depressed Patient Population 2/3 1/3 see never M.D. see M.D.70% of depressed healthcare seekers are seen byprimary care M.D(limited training in mental health) 50% recognized as “mood disorder” 10% appropriately treated with correct: Diagnosis Drug Dosage Duration
2.Why are Mental Health issues Undiagnosed or Underdiagnosed?• Mental illness stigma• Crisis in health care financing(Time constraints: 7-11 minutes/patient )• Clinical diagnosis is difficult – Clinical picture varies: sad, angry, anhedonic – Disease is cyclical – Many criteria on which to judge diagnosis• Primary care patients/physicians focus on somatic complaints(on avg.have 1-2 months training in MH) – Sleep disturbances Weight loss/gain – Fatigue Headache – Back pain Gastrointestinal symptoms
3.Overutilization of wrong resources10% of highest utilizers of PC consumed 50% of $$$ (Top 10% Visitors to Primary Care Physicians) Top 10% use 50% of financial resources(50% have Mental Health Issues)
Consequences• Premature Death from • Impact of family and Health Decline Community• Complications,suicide, • Employment and alcohol and substance financial productivity use/abuse • Other• Quality of life issues
Phases of Treatment Full Recovery Remission Recurrence No Depression Relapse Relapse Severity Symptoms Response Syndrome Pro to gre d is ss ord ion er Acute ContinuationMaintenance Treatment Phases TimeAdapted from: Kupfer DJ. J Clin Psychiatry. 1991(May);52(suppl):28-34
Depression Is a Chronic Illness Recurrent Episodes (%) 100 90% 80% Probability of 50% 50 0 After 1 After 2 After 3 Episode Episodes EpisodesKupfer DJ. J Clin Psychiatry. 1991(May);52(suppl):28-34
RISK FACTORS FORDEPRESSION AND ANXIETY GENETIC FAMILY HISTORY e.g.,SYSTEMIC ILLNESS SOMATIC CHRONIC PAIN, ENDOCRINE DISORDER PSYCHOLOGICAL e.g., LOW SELF-ESTEEM, POOR COPING SKILLS ENVIRONMENTAL e.g., UNEMPLOYMENT, DIVORCE, ABUSE, BEREAVEMENT
Impact on Health andWellness of untreated Depression
Effects of Depression on Medical Disorders• Depression increases likelihood of development of coronary artery disease(heart disease)• Depression worsens outcome after myocardial infarction(heart attacks)• Depression increases risk of stroke• Depression worsens outcome post-stroke• Depression may increase risk of other medical disorders including diabetes, cancer,arthritis• Depression may worsen outcome of cancer, diabetes, AIDS, and other disorders(Immune disorders ,allergies,etc.)• Depression increases risk of cognitive issues and Dementia
Evidence of Hippocampal Atrophy and Loss in Patients With MDD • Compared to controls, patients with depression had smaller hippocampal volumes (n=16)1 • Decreased hippocampal volume may be related to the duration of depression2-41. Bremner JD, et al. Am J Psychiatry. 2000;157(1):115-118. Images courtesy of JD Bremner.2. Sheline YI, et al. J Neurosci. 1999;19:5034-5043.3. Sheline YI, et al. Proc Natl Acad Sci USA. 1996;93:3908-3913.4. Sheline YI, et al. Am J Psychiatry. 2003;160:1516-1518.
Correlation Between Hippocampal Volume and Duration of Untreated Depression 38 Female Outpatients With Recurrent Depression in Remission Total Hippocampal Volume (mm3) 6000 R2=.28 *P=.0006 N=38 5500 5000 4500 4000 3500 3000 0 1000 2000 3000 4000 Days of Untreated Depression • There was a significant inverse relationship between total hippocampal volume and the length of time depression went untreatedSheline YI, et al. Am J Psychiatry. 2003;160(8):1516-1518. Reprinted with permission from APA.
Beyond the Synapse: Brain-derived Neurotrophic Factor (BDNF), Depression, and Antidepressants• Neurogenesis (the birth of new neurons) continues postnatally and into adulthood • BDNF is associated with production of new neurons and their growth and development1 • Data suggest that neurogenesis occurs in the hippocampus2• The hippocampi appear to have important functions related to both mood and memory • Data from depressed patients have shown reduced hippocampal volume3• BDNF may influence regulation of mood4• BDNF is downregulated in MDD and increased with successful antidepressant treatment4,5• Both 5-HT and NE are believed to play roles in the modulation of BDNF1,5 1. Duman RS, et al. Arch Gen Psychiatry. 1997;54(7):597-606. 5. Maletic V, et al. Int J Clin Pract. 2007;61:2030-2040. 2. Gould E, et al. Biol Psychiatry. 2000;48(8):715-720. 3. Sheline YI, et al. Proc Natl Acad Sci U S A. 1996;93(9):3908-3913. 4. Shimizu E, et al. Biol Psychiatry. 2003;54(1):70-75. Image courtesy of RIKEN Institute.
The Role of BDNF in Neuronal Changes in Depression1-3 Stress Production of Increased Activity Inflammatory Cytokines of HPA Axis and Catecholamines Increased Secretion of Glucocorticoids BDNF • Decreased Dendritic• Normal Survival Branching and Growth • Atrophy/Death of NeuronsHPA = hypothalamic pituitary adrenal axis1. Duman RS, et al. Biol Psychiatry. 2000;59:732-739.2. Sapolsky RM. Arch Gen Psychiatry. 2000;57;925-935.3. Maletic V, et al. Int J Clin Pract. 2007;61:2030-2040.
Antidepressants and Neurotrophic Factors May Help Restore Communication in MDDMicrograph Micrograph Hippocampal Pyramidal Neurons1,2 Reduced: Increased: • Dendritic arborization > < • Dendritic arborization • BDNF expression > < • BDNF expression1. Adapted from: Nestler EJ, et al. Neuron. 2002;34:13-25. Images reprinted with permission from Elsevier.2. Adapted from: Manji HK, et al. Biol Psychiatry. 2003;53:707-742.
“Designer Treatment of the 21st Century” Developments in the Medical Treatment of Depression Pharmacologic Refinements “Black TCAs Bile” MAOIs ECT/Analysis SSRI/SNRIs1 st Century 1900 1930s 1950s 80/90’s TMS
Treatment Requires UnderstandingNeurotransmittersoffer a crucialconceptual bridgebetween the mindand the brain.
Axon Terminals Of Serotonergic Neurons Project To Virtually All Portions Of The Brain Thalamus Cingulum Cingulate Gyrus Striatum To Hippocampus NeocortexVentral StriatumAmygdaloid Body Hypothalamus Cerebellar Cortex Intracerebellar Nucle Olfactory And Entorhinal Cortices Caudal Raphe Nuclei Hippocampus To Spinal Cord Rostral Raphe Nuclei
But Wait Do We Have Perfect Well-Tolerated Anti- Depressants? That are well tolerated? And Work often?
Adequate Treatment Is Difficult to Achieve Unmet Medical Needs Adequate Adequate • Adequacy of treatment Dosage Duration has been estimated Factors contributing to inadequate treatment include: to be as low as 18%, regardless of agent used Lack of adherence Poor to recommended tolerability • The ratio of inadequate- treatment to-adequate treatment Medical and attempts is 4:1 Lack of efficacy Psychiatric Comorbidities …adequate treatment in depression is the exception, not the normNemeroff (1996/1997) Depress Anxiety; Oquendo (2003) J Clin Psychiatry; Oquendo (1999) Am J Psychiatry.
STAR*D Study demonstrates that current treatment has limited effectiveness Unmet Medical NeedsTrivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry
Likelihood of discontinuing treatment increases with each new medication attempt Unmet Medical Needs Systemic Drug Side Effects Weight Gain Fatigue Constipation Headache/ Migraine Diarrhea Abnormal Nausea Ejaculation Drowsiness Impotence Insomnia Sweating Decreased Tremor Libido Treatment Nervous Discontinuation Anxiety Side Effects Increased Weakness Appetite Dry Mouth Decreased Appetite DizzinessTrivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) AmJ Psychiatry; Neuronetics, Inc. (data on file)
Technology (to the rescue) • Education • Recognition • Effective treatment that is well received • Medically based Treatment • Short term and successful • No systemic side effects
NeuroStar TMS Therapy A Proven Approach
Best Practices Treatment Guideline for Depression Based on 2010 APA practice guidelines and NeuroStar TMS Therapy® indication for use. Unmet Medical NeedsAdapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010)
Treating the Brain as an Electrochemical Target A Proven Anterior Cingulate Gyrus Approach Prefrontal Cortex Brain activity can be altered: • Chemically (eg, via drugs) or, • Electrically (eg, via TMS) Ventromedial Prefrontal Cortex – Drug action is anatomically Amygdala diffuse and systemic – TMS is focused, non-invasive and non-systemic Major brain regions known to be involved in mood regulationPizzigalli (2011) Neuropsychopharmacology
Transcranial Magnetic Stimulation (TMS) A Proven Approach The treatment coil produces MRI-strength magnetic field pulses. Magnetic field pulses pass unimpeded through the cranium for 2-3 cm. and induce a small electric current. Induced electric currents stimulate the firing of nearby neurons, causing the release of neurotransmitters and clinical effects. 52Faraday (1839) Experimental Research in Electricity. Vol 1; Barker (1991) J Clin Neurophysiol; Barker (1985) Lancet
Targeted Effects on Mood Circuits in Brain A Proven Approach L R TMS Coil L R Activation of fronto-cingulate brain circuit following a course of TMS applied to the left dorsolateral prefrontal cortex in patients with Major Depression 53Kito (2008) J Neuropsychiatry Clin Neurosci
NeuroStar TMSTherapy Demonstration Video
TMS Therapy in Clinical Practice A Proven Approach• Only TMS device FDA-cleared for the treatment of depression• Non-invasive and non-systemic• The most common side effect associated with treatment is scalp pain or discomfort – generally mild to moderate• Outpatient procedure, can be performed in a psychiatrist’s office; no anesthesia or sedation• 37 minute treatment, administered daily for 4-6 weeks• Observed therapy facilitates adherence with treatment• Available by prescription only 55
NeuroStar TMS Therapy:Role of NeuroStar TMS in the Treatment for Major Depression
TMS is Included in Practice Guidelines Following Failure of Initial Treatment Where It Guideline Sources Fits American Psychiatric Association (2010) “…Acute phase treatment may include pharmacotherapy, depression-focused psychotherapy, the combination of medications and psychotherapy, or other somatic therapies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or light therapy…” Guideline Sources World Federation of Canadian Network Institute for Clinical Societies for for Mood and Systems Biological Psychiatry Anxiety Treatments Improvement (2009) (2009) (2010)Schlaepfer, et al. World J Biol Psychiatry (2009); Kennedy, et al J Aff Disorders (2009); Institute forClinical Systems Improvement (2010); American Psychiatric Association (2010)
NeuroStar TMS Practice Locations >300 Systems Installed as of December 2011 Private Practices Institutions
SILICON VALLEY TMSWWW.SILICONVALLEYTMS.COM• Fastest growing and busiest center in Northern California• 2nd Treatment system recently added• Center of Excellence• S.A.Shakir,MD medical director(founder)• 20 clinicians/technical integrated team including MD,NP’s,Psychology,Counselors,Nursing etc.• Many Patients already treated very successfully
TMS Express:Brain BoosterDepression Buster Therapy(BBDBT)Available in 5 or 10 Treatment PackageUsed for quick control of breakthrough or residual depressionin patients already under treatment as an adjunctive depressionDissolving therapyDeveloped by Silicon Valley TMS
Silicon Valley TMS www.siliconvalleytms.com “International Center of excellence”• National Presentations (Numerous)• International Presentations• Nazareth,Palestine Nov.2011• Dubai,UAE, April 2012• Istanbul,Turkey July 2012• Beirut,Lebanon,July 2012• Others in the horizon?
For more informationwww.siliconvalleytms.com. or www.NeuroStar.com Thank you!
THANK YOU QUESTIONS???? (408)email@example.com