The Significant Promise of Therapeutic Neuromodulation: Implications for Psychiatric Mental (PMH) Health Nursing Mary Rosedale PhD, PMHNP BC Donna Ecklesdafer, MSN, RN Theresa Kormos, MSN, PMHCNS BC Michelle Freedland MSN, PMHNP BC Michelle Knapp, MSNPMHNP BC Disclosures Rosedale: Edith L. Fisch Award for Innovation in Neurostimulation, New York University, School of Medicine NYU College of Nursing Pless Center for Nursing Research CTSI Grant # 5UL1RR029893. Supported in part by grant 1UL1RR029893 from the National Center for Research Resources, National Institutes of Health Objectives 1. Describe how neuromodulation aims to regulate neurotransmitters and downstream neurochemical cascades; 2. Examine the safety and efficacy of DBS, VNS, ECT, deep TMS, TMS and tdcs; 3. Identify opportunities for advancing the science of neuromodulation in PMH nursing and nursing research. The Brain as an Electrical and Chemical Organ 100 billion neurons 100 trillion connections Interaction is a combination of electrical and chemical interaction An electrical impulse along an axon Excitatory or inhibitory Threshold= The level of stimulation needed to trigger an action potential Brain Stimulation Techniques Electroconvulsive Therapy (ECT) Vagus Nerve Stimulation (VNS) Repetitive Transcranial Magnetic Stimulation (rtms) Deep Brain Stimulation (DBS) Epidural Cortical Stimulation (EpCS) Transcranial Direct Current Stimulation (tdcs) 6 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 1
Survey of the major neurotransmitters excitatory presynaptic neuron Inhibitory GABA presynaptic neuron Inhibitory neurotrans mission prevents excitation of the postsynaptic neuron Postsynaptic neuron inhibitory 9 10 Mayberg, HS, 1999 11 Drevets, WC 2001 12 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 2
Depression Neurogenesis & Neuroplasticity Cerebral blood flow & Metabolism Hippocampal volume Serotonin Dopamine Neuroplasticity The ability of the neural pathways and synapses to adapt to stimuli by reorganizing structurally and functionally. 13 Neurogenesis The birth of new neurons mostly known to occur in the dentate gyrus of the hippocampal formation. 14 ECT Plasma prolactin levels Thyrotropin releasing hormone (TRH) TRH receptor function Brain derived neurotrophic factor (BDNF) 15 TMS Cerebral blood flow in the prefrontal & paralimbic areas Dopamine Serotonin Thyroid stimulating hormone (TSH) Glutamate levels GABA 16 Electroconvulsive Therapy (ECT) Donna Ecklesdafer, MSN, BSN, RN ECT Clinic Manager Pine Rest Christian Mental Health Services 17 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 3
Diagnoses Diagnoses Major Depression (+/ psychosis) Other diagnoses Bipolar Depression and Mania Schizoaffective Catatonia Neuroleptic Malignant Syndrome Dementia with underlying mood disorder Current research project Short term Efficacy and Cognitive Side Effects of Acute Electroconvulsive Therapy for Agitation and Aggression in Dementia Actively Suicidal Life Saving Treatment Rapid Response Needed Suicide (National Institute of Mental Health, Jan. 11, 2011) 34,598 cases reported in 2007 (latest report) Over 90% diagnosed with Depressive Disorder or Substance Abuse Disorder Suicide (National Institute of Mental Health, Sept 11, 2011) The overall rate was 11.3 suicide deaths per 100,000 people. An estimated 11 attempted suicides occur per every suicide death. Children ages 10 to 14 0.9 per 100,000 Adolescents ages 15 to 19 6.9 per 100,000 Young adults ages 20 to 24 12.7 per 100,000 Older adults ages 65 and older 14.3 per 100,000 Older non Hispanic white males 85 and older 47 per 100,000 Medications Anesthesia Muscle Relaxant Improvements in ECT Oxygenation Administration of oxygen Monitor oxygen saturation Improvements in ECT Type of electricity brief pulse wave Seizure monitoring Stimulus dosing Ultra brief pulse Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 4
Stimulus Electrode Placements Seizure Monitoring Bi temporal Right Unilateral Bifrontal Seizure length 30 60 seconds Tonic/Clonic (Peripheral seizure) Tachycardia Electroencephalogram (EEG) (Central seizure) ECT Treatments Acute Series 3 times each week Typically 6 12 treatments Improvements seen after 4 6 treatments Maintenance Weekly to monthly Can prevent inpatient stays 80% of patients relapse after ECT with no follow up of medications or maintenance ECT Seizure Threshold Medications that can change seizure threshold Lithium Benzodiazepines Mood stabilizers Antipsychotics Seizure Threshold Other influences on seizure threshold Age Gender Electrode placement Hyperventilation Dehydration Sleep Seizures Parasympathetic discharge Sympathetic discharge Potential rebound parasympathetic discharge Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 5
Anesthesia Anesthetic Brevital or methohexital Etomidate Muscle relaxant succinylcholine (anectine) Potential Mechanisms of Action Decreases frontal cortical connectivity Neurotransmitter theory Depolarizing muscle relaxant Anticonvulsant theory Most common cause of muscle soreness Benefits of ECT Potential Side Effects Improved mood Increased pleasure More restful sleep Better appetite More positive attitude Less agitation Increased sexual interest More energy Clearer thinking More hope Headache and muscle aches Nausea Unsteady on feet Confusion Potential short term and/or long term memory loss Contraindications No absolute contraindications High risk Risk versus benefit Mortality Less than for childbirth Pre ECT Workup Psychiatric referral Basic Metabolic Profile Electrocardiogram History & Physical medical clearance Inpatient versus Outpatient Risk/Benefit Ratio Education Informed Consent Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 6
Patient and Family rating scale Assessment of patient Intravenous line placement Anesthesia and muscle relaxant Brief electrical stimulus Monitor seizure activity ECT Procedure Transcranial Magnetic Stimulation (TMS) Therapy Indicated for the treatment of Major Depressive Disorder (MDD) in adult patients Is non invasive, generally well tolerated (Barker & Jalinous, 1985) Utilizes a magnetic field generated by a treatment coil applied to the head, usually 1.5 3.0 tesla (Higgins & George, 2009 ) Post Anesthesia Care Unit Vitals stable discharge Neuronetics TMS machine generates 0.5 tesla (Neuronetics, Inc., 2010) 38 TMS Therapy For comparison, 3.0 T is strength of magnetic field generated by most medical Magnetic Resonance Imaging (MRI) systems in use (Higgins & George, 2009) Early Transcranial Magnetic Stimulation TMS produces its effect through electrical stimulation of the area of the brain believed to be responsible for mood (Neuronetics, Inc., 2010 ) 3 Barker & Jalinous, 1985 40 How Does TMS work? Picture from Manufacturer: Neuronetics Electric energy within insulated coil induces magnetic fields Magnetic fields penetrate the the cranium 1.5 2.0 cm below the device Magnetic fields induce electric current in the brain Which leads to depolarization of nerve cells causing release of neurotransmitters (Higgins ES, George MS, 2009; 41 Neuronetics, Inc., 2010) Identifying TMS Treatment Location Coil applied to the Primary Motor Cortex area of the brain to elicit thumb twitch Called Motor Threshold (MT) MT determines energy required to effectively treat depression, as well as helps identify location of Dorsolateral Prefrontal Cortex (DLPFC) 42 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 7
Dorsolateral Prefontal Cortex (DLPFC) Area of the brain believed to be responsible for regulating mood (Baeken C, De Raedt R. 2011; Dell Osso, et al., 2011) 43 TMS Manufacturers Brainsway (Israel), www.brainsway.com CR Tech (Seoul, South Korea) Magstim Company, Ltd. (Whitland, UK) ww.magstim.com MAG&MORE GmbH, (Munich, Germany) Mcube Technology Co., Ltd. (Seoul, South Korea) Medtronic Dantec NeuroMuscular (Skovlunde, Denmark) www.medtronic.com Neuralieve (California, USA) www.neuralieve.com Neuronetics Inc., www.neuronetics.com Nexstim (Finland) www.nexstim.com Schwarzer (München, Germany) www.schwarzer.net 44 FDA Labeling NeuroStar TMS Therapy System is a prescription device under 21 CFR Part 801.109 that is indicated for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode. NeuroStar TMS Therapy System (Picture from Manufacturer: Neuronetics) Treatment Coil Display (Neuronetics, Inc., 2010) Senstar Treatment Link Mobile Console 45 46 TMS Administration Recommended Intensity 120% of MT Frequency pulses per second (10 Hz or 1 Hz) Stimulation time 4 seconds, with 26 second rest time; 3000 total pulses per treatment Patient Selection for TMS Pt with MDD who has failed one trial of antidepressant at or above minimally effective dose, for a minimal duration (at least 4 weeks) in the current episode of MDD Pt has no history of seizures, no ferromagnetic metal objects or shrapnel above the shoulders, no implantable medical devices; for instance: TMS sessions 1 per day for 4 6 weeks. 47 48 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 8
Patient Selection for TMS Con t Pacemakers, or other implanted physiologic devices; coronary artery stents, aneurysm coils and clips; cochlear implants are contraindicated for use of TMS No metallic tattoos; permanent makeup should be > 30 cm from coil Clinical Considerations Performed as an in /outpatient procedure Patient is awake, alert during treatment Treatment lasts about 40 minutes, patient resumes normal activity afterwards 49 Many TMS patients continue to take psychotropic medications Insurance may cover TMS on case by case basis 50 Clinical Considerations Common Side Effects Scalp discomfort, tenderness at coil placement site TMS Remission Rates: Neuronetics Trial and NIMH OPT TMS Study O'Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 2007; 62:1208 1216. George MS, Lisanby SH, Avery D, et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a shamcontrolled randomized trial. Arch Gen Psychiatry 2010; 67:507 516. Headache, may be managed with OTC analgesic of choice 14 % 14.2 14.1 Facial pain, muscle twitching 5% 5.2 5.1 Active Sham Active Sham 51 Neuronetics OPT TMS 52 Response, Remission, Non Response Rates for TMS pts at WRNMMC Response 50% reduction in baseline mood scale score (PHQ 9, QIDS SR): 44.4%. Of those who responded, 3 of 4 met criteria for full remission of MDD symptoms Remission Full resolution of depressive symptoms (PHQ 9 score < 5, QIDS SR < 6) Non Response rate at WRNMMC after 20+ TMS sessions: 44.4% TMS: Who does What? TMS machine is a class II device prescribed by MD, NP Each state regulates prescriptive authority which includes nurse practitioners Providers with prescriptive authority dictate the dose of TMS, other operators may administer TMS treatment Ideally, person administering TMS is medically trained and able to manage a seizure 53 54 Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 9
Why PHM RN Role in TMS is Important Monitor for patient safety and effective treatment Allows for close, daily patient assessment Coordinate care with outpatient providers Crisis intervention as needed 55 References 1. Baeken C, De Raedt R. Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression. Dialogues in Clinical Neuroscience 2011; 13(1): 139 145. 2. Barker AT, Jalinous R. Non invasive magnetic stimulation of human motor cortex. Lancet 1985 (May 11, 1985): 1106 1107 3. Dell Osso B, Camuri G, Castellano F, Vecchi V, Benedetti M, Bortolussi S, Altamura AC. Meta review of metanalytic studied with repetitive transcranial magnetic stimulation (rtms) for the treatment of major depression. Clinical Practice & Epidemiology in Mental Health 2011; 7: 167 177. 4. Epilepsy Foundation of America, Inc. 2009. Managing seizures: Information for caregivers. 5. George MS, Belmaker RH (editors). Transcranial Magnetic Stimulation in Clinical Psychiatry. Arlington, VA: American Psychiatric Publishing, 2007. 6. Higgins ES, George MS. Brain Stimulation Therapies for Clinicians. Washington, DC: American Psychiatric Publishing, Inc., 2009 7. The New Yorker Cartoons of the Year. New York, NY, 2011. 56 Deep & Cortical Brain Stimulation (Pictures from Manufacturers: Medtronic, NeuroPace) Bilateral Epidural Prefrontal Cortical Stimulation for TRD (Pictures Provided by Manufacturer: Synergy) NeuroPace Medtronic 57 58 Cognition, executive control and integration of emotion: 2 complimentary networks (Picture Provided by Manufacturer: Synergy) VN S 59 Picture Provided by Manufacturer: Cyberonics Cyberonics, Inc., Houston, TX Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 10
Overlapping Paradigm Shifts in Nursing and Brain Stimulation 50 years is needed to make a paradigm shift In the past 6 decades, Nursing has been transformed from an occupation where nurses do to and for patients, to a profession where nurses work with patients For more than 7 decades, nurses have provided specialized care for ECT patients Brain stimulation therapies are a new therapeutic class and Psychiatric Nursing The Science is Moving at Accelerated Rate: Changing Practice and Knowledge Development O Reardon (2010). International Society of ECT and Neurostimulation. field Mayberg et al 1999 tdcs for Depression (Rigonnati et al., 2008 & Fregni et al., 2006 Transcranial Direct Current Stimulation in HIV Infected, Depressed Persons 63 tdcs was an Safe, effective and tolerable treatment in 7 HIV patients with co morbid major depression and associated with significant (P <.05) decreases in HAMD 24 and MADRAS scores Knotkova, Rosedale et al., 2012) Using transcranial direct current stimulation (tdcs) to treat depression in HIV infected persons: The outcomes of a feasibility study. Frontiers in Neuropsychiatric Imaging and Stimulation, 3(59), 1 8. Safety, Tolerability and Feasibility of tdcs for HIV+ Persons Racial and Ethnic Minorities with MDD A Treatment Wish List 10 sessions over PFC Phoressor II 850 PM using 2 electrodes (36cm 2 ) placed over F3 position of EEG 10 20 system and the contralateral supraorbital region. Recruit racial/ethnic minorities HamD 24 and MADRAS Cytokine assays Analyze characteristics of completers/ non completers Conduct qualitative interviews to incorporate subject input in future patient centered treatment protocols Open label, 2 week block of tdcs (Baker, Rorden, & Fridriksson, 2010; Stroke) An evidence based treatment for depression and pain Focus and dose that can be personalized Faster onset than medications Acceptable to those who cannot tolerate medications due to side effects, med interactions and comorbidities Adjuvant treatment for those reporting partial relief from other treatments (safely combined/optimizing response) Feasible for patients with low performance status (minimal patient effort or attention) Clinically tested in racial and ethnic minorities Well tolerated, brief, safe, easy to administer and inexpensive Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 11
<20 20-24 25-29 30-34 35-39 40-44 45-49 50-54 There is a very specific kind of pain to depression and it became less vicious. It was not that pain changed: the perception of pain changed Rosedale, Lisanby& Malaspina(2009) Research Brief: The structure of the lived experience for persons having undergone rtms for depression treatment. Journal of the American Psychiatric Nurses Association,15(5), 333 337., Key Issues: Reclassification of ECT by FDA and APNA s Position Statement ECT as evidence-based practice Unparalleled efficacy of ECT and dangers of limiting access Evolution of ECT and Brain Stimulation Misinformation and stigma of psychiatric conditions and treatments Key Issues at FDA hearings APNA s Vital Leadership Role and Position 68 How History of Brain Stimulation Shapes Psychiatric Nursing s Future Advancing Evidence-based practice Combining Psychotherapeutic Treatments Combining Qualitative and Qualitative Approaches Treating new populations Advocating for Our Patients Influencing Public Policy 69 APA ECT Task Force: APNA Consultation on Nurse s Role Second edition (2001) American Psychiatric Association, Task Force, (2001). Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. ISBN 10: 0890422060 Third edition (2013) Evidence-based Nursing Practice and APN roles Accurately representing the wealth of psychiatric nursing expertise and the contributions of nursing profession Life Long Neurogenesis: Hardy, C., Rosedale, M., Messinger, J., Goetz, R.R., Malaspina, D. (2012). Olfactory Acuity Associated with Mood and Function in a Pilot Study of Stable Bipolar Patients. Bipolar Disorders. 4(1):109 17. Olfactory System Olfactory Epithelium Culture Olfactory Neurons Gene Expression Studies Potential for Stem cells Hippocampus Translational Neuroscience Research Malaspina, D. (2012) Neurobiologyfoundation.org Clinical Research Epidemiology 3.5 3 2.5 2 1.5 1 0.5 0 Age of mother Age of father Basic Science Animal Models Hippocampal Dentate Gyrus Coronal and sagital 7T 100 micron cell layer Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 12
Psychiatric Nursing and Brain Stimulation: Back to the Future Pictures Provided by Medical University of South Carolina Rosedale, Ecklesdafer, Kormos, Freedland, Knapp 13