Next Generation Antidepressants: Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders PDF
Preview Next Generation Antidepressants: Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders
The World Health Organization defines depression as one of the primary B contributors to the global burden of disease and predicts it will become the e y second leading cause of death by the year 2020. The need to develop effective e therapies has never been so pressing. r Next Generation a Current antidepressant drugs are moderately effective in certain patient n d populations; however, they have a number of limitations, including delayed onset S of efficacy, treatment resistance and deleterious side effects. t a Antidepressants The focus of this book is to look forward at the future of mood-disorder h l research, covering the identification of new therapeutic targets, establishing new preclinical models, new medicinal chemistry opportunities, and fostering greater understanding of genetic influences. These strategies are likely to help N build a better picture of the disease process, and lead to new opportunities for e Moving Beyond Monoamines to Discover Novel patient stratification and treatment. x t Treatment Strategies for Mood Disorders The ultimate goal for this strand of research is to develop more personalized G and effective treatments for this chronic and debilitating condition. e This will be essential reading for all those involved in psychopharmacologic n drug development, as well as for mental health clinicians seeking a preview e Edited by Chad E. Beyer of discoveries soon to influence their practice. r a t and Stephen M. Stahl Chad E. Beyer is Director of Medications Development at Lohocla Research, i o and Associate Professor of Research in the Department of Pharmacology at n the University of Colorado School of Medicine, Aurora, Colorado, USA. A Stephen M. Stahl is Adjunct Professor of Psychiatry at the University of n California San Diego, San Diego, CA, USA, and Honorary Visiting Senior Fellow t i in Psychiatry at the University of Cambridge, Cambridge, UK. d e p Other titles of interest: r Stahl’s Illustrated Antipsychotics, Second Edition e Stephen M. Stahl and Laurence Mignon (ISBN 9780521149051) s s The Overlap of Affective and Schizophrenic Spectra a Edited by Andreas Marneros and Hagop S. Akiskal (ISBN 9780521108713) n t Antipsychotic Trials in Schizophrenia: The CATIE Project s Edited by T. Scott Stroup and Jeffrey A. Lieberman (ISBN 9780521895330) Evidence-based Psychopharmacology Edited by Dan J. Stein, Bernard Lerer, and Stephen M. Stahl (ISBN 9780521531887) Cover illustrations: DNA image: iStockphoto/ Andrey Prokhorov; flask image: iStockphoto/ Pierre-Emmanuel; coloured CT scan of a healthy brain (side view):Pasieka/Science Photo Library. BEYER: Next Generation Antidepressants PPC C M Y BLK Next Generation Antidepressants Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders Download more eBooks here: http://avaxhome.ws/blogs/ChrisRedfield Next Generation Antidepressants Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders Edited by Chad E. Beyer DepartmentofPharmacology,UniversityofColoradoSchoolofMedicineAurora,CO,USA and Stephen M. Stahl DepartmentofPsychiatry,UniversityofCaliforniaSanDiegoandNeuroscienceEducationInstituteCalifornia,USA CAMBRIDGE UNIVERSITY PRESS Cambridge,NewYork,Melbourne,Madrid,CapeTown,Singapore, SãoPaulo,Delhi,Dubai,Tokyo CambridgeUniversityPress TheEdinburghBuilding,CambridgeCB28RU,UK PublishedintheUnitedStatesofAmericabyCambridgeUniversityPress,NewYork www.cambridge.org Informationonthistitle:www.cambridge.org/9780521760584 ©CambridgeUniversityPress2010 Thispublicationisincopyright.Subjecttostatutoryexception andtotheprovisionsofrelevantcollectivelicensingagreements, noreproductionofanypartmaytakeplacewithoutthewritten permissionofCambridgeUniversityPress. Firstpublished2010 PrintedintheUnitedKingdomattheUniversityPress,Cambridge AcatalogrecordforthispublicationisavailablefromtheBritishLibrary ISBN978-0-521-76058-4Hardback CambridgeUniversityPresshasnoresponsibilityforthepersistenceor accuracyofURLsforexternalorthird-partyinternetwebsitesreferredto inthispublication,anddoesnotguaranteethatanycontentonsuch websitesis,orwillremain,accurateorappropriate. Everyefforthasbeenmadeinpreparingthisbooktoprovideaccurateandup-to-date informationwhichisinaccordwithacceptedstandardsandpracticeatthetimeofpublication. Althoughcasehistoriesaredrawnfromactualcases,everyefforthasbeenmadetodisguisetheidentities oftheindividualsinvolved.Nevertheless,theauthors,editors,andpublisherscanmakenowarranties thattheinformationcontainedhereinistotallyfreefromerror,notleastbecauseclinicalstandardsare constantlychangingthroughresearchandregulation.Theauthors,editors,andpublisherstherefore disclaimallliabilityfordirectorconsequentialdamagesresultingfromtheuseofmaterialcontainedin thisbook.Readersarestronglyadvisedtopaycarefulattentiontoinformationprovidedbythe manufacturerofanydrugsorequipmentthattheyplantouse. Contents Listofcontributors pagevi Preface ix ChadE.Beyer Listofabbreviations x 1 Currentdepressionlandscape: 5 Definingdepression astateofthefieldtoday 1 endophenotypes 70 LaurenceMignonandStephen LisaH.BerghorstandDiego M.Stahl A.Pizzagalli 2 Noveltherapeutictargetsfor 6 Geneticandgenomicstudies treatingaffectivedisorders 12 ofmajordepressivedisorder 90 EliyahuDremencovandThomas RoyH.Perlis I.F.H.Cremers 7 Medicinalchemistrychallenges 3 Developingnovelanimalmodels inthedesignofnextgeneration ofdepression 28 antidepressants 102 LottedeGroote,Malgorzata DavidP.Rotella Filip,andAndrew 8 Applicationofpharmacogenomics C.McCreary andpersonalizedmedicinefor 4 Translationalresearchinmood thecareofdepression 119 disorders:usingimaging Keh-MingLin,Chun-YuChen, technologiesinbiomarker andYu-JuiYvonneWan research 45 JulLeaShamy,AdamM.Brickman, ChrisD.Griesemer,Anna Parachikova,andMarkDay Index 132 v Contributors LisaH.Berghorst,MA LottedeGroote,PhD DepartmentofPsychology,Harvard SolvayPharmaceuticalsResearch University,Cambridge,MA,USA Laboratories,Weesp,TheNetherlands ChadE.Beyer,PhD,MBA Keh-MingLin,MD,MPH DepartmentofPharmacology,Universityof CenterforAdvancedStudyinthe ColoradoSchoolofMedicine,Aurora,CO, BehavioralScience,Stanford,California, USA USA,andDivisionofMentalHealth andAddictionMedicine,National AdamM.Brickman,PhD HealthResearchInstitutes(NHRI), TheTaubInstituteforResearchon Taipei,Taiwan Alzheimer’sDiseaseandtheAgingBrain, ColumbiaUniversity,NewYork,NY,USA AndrewC.McCreary,PhD SolvayPharmaceuticalsResearch Chun-YuChen,MS Laboratories,Weesp,TheNetherlands DivisionofMentalHealthandAddiction Medicine,NationalHealthResearch LaurenceMignon,PhD Institutes(NHRI),Taipei,Taiwan NeuroscienceEducationInstitute,Carlsbad, CA,USA ThomasI.F.H.Cremers,PhD BrainsOn-LineBV,TheNetherlands,and AnnaParachikova,PhD BrainsOn-LineLLC,SanFrancisco,CA CognitiveNeuroscience,PsychoGenics,Inc, Tarrytown,NY,USA MarkDay,PhD ExperimentalNeuroimaging,Abbott RoyH.Perlis,MD,MSc Laboratories,AbbottPark,IL,USA LaboratoryofPsychiatric Pharmacogenomics,CenterforHuman EliyahuDremencov,PhD GeneticResearch,MassachusettsGeneral BrainsOn-LineBV,Groningen,The Hospital,Boston,MA,USA Netherlands DiegoA.Pizzagalli,PhD MalgorzataFilip,PhD,DSc DepartmentofPsychology,Harvard LaboratoryofDrugAddictionPharmacology, University,Cambridge,MA,USA DepartmentofPharmacology,Instituteof Pharmacology,PolishAcademyofSciences, DavidP.Rotella,PhD Krakow,Poland Chemical&ScreeningSciences,Wyeth Research,Princeton,NJ,USA ChrisD.Griesemer,BS TheCenterforMolecularandGenomic JulLeaShamy,PhD Imaging,UniversityofCalifornia,Davis, DrugDiscoveryandDevelopment, CA,USA PsychoGenics,Inc,Tarrytown,NY,USA vi Listofcontributors StephenM.Stahl,MD,PhD Yu-JuiYvonneWan,PhD DepartmentofPsychiatry,University DepartmentofPharmacology, ofCaliforniaSanDiegoand Toxicology&Therapeutics,University NeuroscienceEducationInstitute, ofKansasMedicalCenter,KansasCity, Carlsbad,CA,USA Kansas,USA vii Download more eBooks here: http://avaxhome.ws/blogs/ChrisRedfield Preface AstheWorldHealthOrganizationestimatesthatdepressionwillbecomethesecondleading causeofdeathbytheyear2020–dueprimarilytocomplicationsarisingfromstressandthe cardiovascularsystem–theneedtodevelopnovelandmoreeffectivetreatmentstrategiesfor patientssufferingwithmooddisordershasneverbeenmoreparamount.Currenttreatment optionsfordepressedpatientsincludeavarietyofmoleculesdesignedtoexclusivelyelevate centralnervoussystemlevelsofmonoaminessuchasserotonin(5-HT).Theseclassesinclude the monoamine oxidase inhibitors and tricyclics and are exemplified by the selectivesero- toninreuptakeinhibitors(SSRIs)andthedualserotonin/norepinephrinereuptakeinhibitors (SNRIs).Whilethesemedicinesaremoderatelyeffectiveinsomepatientpopulations,there are still considerable limitations associated with all commercially available antidepressants. Thesedrawbacksinclude,butarenotlimitedto,delayedonsetofefficacy,treatmentresistance inmanypatients,anddeleterioussideeffectssuchasemesisandsexualdysfunction.Thefocus ofthisbookistoreviewthecurrentlandscapeandstateofthefieldfordepressionresearch withaneyetowardssheddinglightonwherethefutureofmooddisordersresearchisheaded in terms of novel therapeutic targets, preclinical model development, exploring depression endophenotypes,andmedicinalchemistrystrategies.Undoubtedlyallofthesedisciplines,as wellasothersincludinggeneticsandtranslationalmedicineapproaches,willneedtosuccess- fullycollaboratetohelpbuildabetterunderstandingofdiseaseetiology,patientstratification, andtreatment.Asdepressionresearchhasevolvedoverthepast50years,thenextdecadewill beinstrumentalinfacilitatingamovebeyondourcurrentunderstandingandpharmacolog- ical treatment options, and strive to discover and develop more personalized and effective treatmentoptionsforthemillionsofpatientssufferingfromchronicanddebilitatingmood disorders. ChadE.Beyer,PhD,MBA DepartmentofPharmacology,UniversityofColoradoSchoolofMedicine,Aurora,CO,USA ix
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