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Acting Antidepressants CME Answer these questions to receive 0.5 AMA PRA Category 1 CreditTM. Chair Test Your Knowledge: The Evidence for GABA-Modulating Neuroactive Kristina M. Deligiannidis, MD Steroids as a New Class of Rapid- Zucker Hillside Hospital, Northwell Health Zucker School of Medicine at Acting Antidepressants Hofstra/Northwell Glen Oaks, New York What’s Inside 3 Neuroactive Steroids: Their Role in GABA-A Receptor Modulation and Implications for Mood Disorders Including PPD and MDD 5 Major Depressive Disorder: Burden of Disease, Diagnostic Challenges, and Gaps in the Current Standard of Care 7 Brief Assessment: Testing Your Knowledge About the Management of Depression During Pregnancy 7 Perinatal Depression: Burden of Disease, Diagnostic Challenges, and Gaps in the Current Standard of Care 110 Novel and Emerging Treatment Options and Ongoing Trials in PPD and MDD Participate in interactive questions, download activity slides, and obtain your instant CME credit online. PeerView.com/SZJ900 Test Your Knowledge: The Evidence for GABA-Modulating Neuroactive Steroids as a New Class of Rapid-Acting Antidepressants Activity Information Activity Description and Educational Objectives Providership, Credit, and Support In this activity, an expert in psychiatry discusses the use of GABA-modulating Penn State College of Medicine is accredited by the Accreditation Council for neuroactive steroids as rapid-acting antidepressants. Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Upon completion of this activity, participants should be better able to: • Discuss the role of GABAergic dysfunction in PPD and MDD and the rationale for The Penn State College of Medicine designates this enduring material for a therapeutic targeting of GABA-A receptors with neuroactive steroids maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit • Review the current treatment landscape and unmet needs of patients with MDD commensurate with the extent of their participation in the activity. • Identify key barriers to the diagnosis and management of PPD • Apply recent evidence on the efficacy and safety of approved and emerging Information about CME credit for this activity is available by contacting Penn State at neuroactive steroids to the management of patients with PPD and MDD 717-531-6483 or [email protected]. Reference course # G6719-21-T. Target Audience This activity is developed in collaboration with our educational partner, PVI, This activity has been designed to meet the educational needs of psychiatrists, PCPs, PeerView Institute for Medical Education. OB/GYNs, and other healthcare professionals involved in the care of patients with major depressive disorder and postpartum depression. Support This activity is supported by an educational grant from Sage Therapeutics. Requirements for Successful Completion In order to receive credit, participants must view the activity and complete the post- Disclosure of Unlabeled Use test and evaluation form. There are no prerequisites and there is no fee to participate The faculty of this educational activity may include discussions of products in this activity or to receive CME credit. Statements of Credit are awarded upon or devices that are not currently labeled for use by the FDA. Faculty members successful completion of the post-test and evaluation form. have been advised to disclose to the audience any reference to an unlabeled or investigational use. Media: Enduring Material Release and Expiration Dates: March 16, 2021 - March 15, 2022 No endorsement of unapproved products or uses is made or implied by coverage Time to Complete: 30 minutes of these products or uses in our reports. No responsibility is taken for errors or omissions in reports. For approved prescribing information, please consult the Faculty and Disclosure / Conflict of Interest Policy manufacturer’s product labeling. In accordance with ACCME requirements, Penn State College of Medicine has a conflict of interest policy that requires faculty to disclose relevant financial About This CME Activity relationships related to the content of their presentations/materials. Any potential PVI, PeerView Institute for Medical Education, and Penn State College of Medicine conflicts are resolved so that presentations are evidence-based and scientifically are responsible for the selection of this activity’s topics, the preparation of editorial balanced. content, and the distribution of this activity. Our activities may contain references to unapproved products or uses of these products in certain jurisdictions. The Chair preparation of PeerView activities is supported by educational grants subject to Kristina M. Deligiannidis, MD written agreements that clearly stipulate and enforce the editorial independence of Director, Women’s Behavioral Health PVI and Penn State College of Medicine. Zucker Hillside Hospital, Northwell Health Associate Professor of Psychiatry and Obstetrics & Gynecology The materials presented here are used with the permission of the authors and/or Zucker School of Medicine at Hofstra/Northwell other sources. These materials do not necessarily reflect the views of PeerView or Glen Oaks, New York any of its partners, providers, and/or supporters. Kristina M. Deligiannidis, MD, has a financial interest/relationship or affiliation in the form of: Consultant and/or Advisor for Sage Therapeutics, Inc. Grant/Research Support from Sage Therapeutics, Inc. and Vorso Corporation. Medical Director Kristin Tomlinson, PhD PVI, PeerView Institute for Medical Education Kristin Tomlinson, PhD, has no financial interests/relationships or affiliations in relation to this activity. Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships. Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships. Go online to complete the post-test and CONNECT WITH US evaluation for CME credit 2 / 14 PeerView.com/SZJ900 Test Your Knowledge: The Evidence for GABA-Modulating Neuroactive Steroids as a New Class of Rapid-Acting Antidepressants Neuroactive Steroids: Their Role in GABA-A Receptor Modulation and Implications for Mood Disorders Including PPD and MDD Question 1 significantly to regulating CNS function. A GABAergic deficit hypothesis of depression has been proposed, implicating GABAergic dysfunction in the underlying neurobiology of mood Which of the following statements is true about brexanolone, the disorders.1-5 There are many lines of evidence that support this first agent to be FDA approved for the treatment of adult women theory by linking GABA to processes that cause depression in with postpartum depression? direct and indirect ways (Figure 1). For example, direct evidence of GABA’s role in the development of depression includes { It is a neuroactive steroid and an exogenous analog to observations from preclinical and clinical research that depression progesterone or depressive-like symptoms are associated with decreased concentrations of GABA in the brain, decreased expression of { It is a positive allosteric modulator of GABA-A synaptic and GABA synthesizing enzymes, altered expression of GABA-A extrasynaptic receptors receptor subunits, a reduction in the number of GABAergic interneurons, and polymorphisms in genes encoding for GABA-A { It is a neuroactive steroid and a GABA-A receptor antagonist receptor subunits.3,5 { It is a positive allosteric modulator of GABA-A that reduces the Indirect links between GABA and depression include but are activity of GABA during periods of chronic stress not limited to GABA’s role in the regulation of the default mode network, important to the clinical expression of deposition; GABA's { I’m not sure role in the regulation of the hypothalamic-pituitary-adrenal, or HPA, axis;4 and the antidepressant effects of neuroactive steroids Introduction such as allopregnanolone.3,6 There are likely shared and differing Major depressive disorder (MDD) and perinatal depression pose pathophysiological mechanisms across MDD and perinatal significant challenges to the health and quality of life of millions depression, and GABAergic neurotransmission regulates the of Americans and their families. Optimal management of MDD activity of diverse brain networks that are implicated in both.4,7 and perinatal depression begins with adequate screening for recognition of the signs and symptoms of these diseases and Figure 1: Role of GABA in Neurobiology of Depression1-6 early introduction of appropriate therapy based on individual patient needs. However, there are several limitations to the GABA system is the major inhibitory signaling pathway of the brain and CNS monoaminergic antidepressant therapies that are considered the Direct evidence of GABA’s role in the development of depression includes standard of care for these conditions, such as slow therapeutic • Decreased concentrations of GABA in the brain response, suboptimal overall efficacy and remission rates, and • Decreased expression of GABA synthesizing enzymes • Altered expression of GABA-A receptor subunits adverse effects that may impact patient adherence. In this activity, • Reduced number of GABAergic interneurons • Polymorphisms in genes encoding for GABA-A receptor subunits Dr. Deligiannidis explores the association between depression and GABAergic dysfunction and examines the rationale for therapeutic Indirect links between GABA and depression include
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