Treatment–Refractory Schizophrenia: A Clinical Conundrum PDF
Preview Treatment–Refractory Schizophrenia: A Clinical Conundrum
Treatment- Refractory Schizophrenia A Clinical Conundrum Peter F. Buckley Fiona Gaughran Editors 123 ‐ Treatment Refractory Schizophrenia ThiSisaFMBlankPage Peter F. Buckley (cid:129) Fiona Gaughran Editors ‐ Treatment Refractory Schizophrenia A Clinical Conundrum Editors PeterF.Buckley FionaGaughran MedicalCollegeofGeorgia InstituteofPsychiatry GeorgiaRegentsUniversity DepartmentofPsychosisStudies Augusta NationalPsychosisUnit Georgia SouthLondonandMaudsley USA NHSFoundationTrust London UnitedKingdom ISBN978-3-642-45256-7 ISBN978-3-642-45257-4(eBook) DOI10.1007/978-3-642-45257-4 SpringerHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2014933953 #Springer-VerlagBerlinHeidelberg2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface It is a far too frequent occurrence that patients with schizophrenia don’t respond adequately or return to function using current pharmacological and non- pharmacological treatment approaches. As schizophrenia is fundamentally characterizedbyrecurrentrelapses,theextenttowhicharefractorytreatmentstatus represents a de novo, more severe form of psychosis or occurs in evolution over the course of a deteriorative illness is a fundamental consideration. Biological studies reveal a range of deficits and support, at least in part, the proposition that treatment-refractoriness worsens over time. Our field has struggled about when to introduce clozapine, the gold-standard antipsychotic medication for treatment- refractory schizophrenia, and at present this “drug of choice” is more often than not introduced too late in the course of illness. One reason for this is the highly variable efficacy of other antipsychotics in people where one anti-psychotic has alreadyfailed,withthesequentialavailabilityofeachnewantipsychoticseemingto relegateclozapine’spositionevenfurtherawayfromitsuseinearlyillness. Once clozapine is tried, a proportion of patients will inevitably have an unsatisfactory outcome and how best to next treat these patients remains subject to clinical debate. A range of adjunctive medication strategies has been tried with variable success. The coming on line of new neuromodulatory approaches (e.g., repetitive transcranial magnetic stimulation) has provided more treatment options as well as renewed interest in the role of electroconvulsive therapy in this patient population. Cognitive and vocational approaches represent another avenue to bolster improved outcomes. Families play a fundamental role in advancingbetteroutcomesinpatientswithrecalcitrantschizophrenia.Unfortunately, one consequence of chronic and inadequately treated active psychosis is the propensity for poorer social outcomes. This remains a real source of concern, emphasizing just how far we have yet to travel on the journey toward effective, comprehensive, and well-integrated care for people with severe schizophrenia. Perhaps the emergence of pharmacogenetic approaches to individualized care might“movethedial”furthertowardbetterindividualoutcomes. This book, with thirteen authoritative chapters by leading experts from across the globe, provides a timely overview of the current options for treatment ofmostseverelyillpatientswithschizophreniaandapeekintofuturepossibilities. v vi Preface Thebookisclinicallyfocused,withaviewtohelpingtheclinicianapplythelatest research evidence in both neurobiology and psychology to clinical practice. The contentiswide-ranging,coveringcurrentpharmacologicalapproachestotreatment nonresponse and treatment intolerance, various emerging add-on approaches, and arangeofcognitiveandpsychosocialtreatments.Thecontributorsarehighlyregarded expertswhohavetakenatranslationalapproach,meldingclinicalexperiencewith cutting-edge research to provide readers with an invaluable book on the funda- mentalaspectsofclinicalcareforrefractoryschizophrenia. Augusta,GA PeterF.Buckley London,UK FionaGaughran Contents 1 Treatment-RefractorySchizophrenia:Definition andAssessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 DerekK.TracyandSukhwinderS.Shergill 2 BiologyofSchizophrenia:IsTreatmentRefractorinessSynonymous withSeverityofIllness[A.K.A.IsThisaDrugEfficacyProblem oranExpressionofSevereIllness?]. . . . . . . . . . . . . . . . . . . . . . . . 21 HelioElkisandPeterF.Buckley 3 DopamineandtheBiologyandCourseofTreatmentResistance. . . 31 ArsimeDemjahaandOliverD.Howes 4 MedicalandPsychiatricComorbidities:ComplicatingTreatment Expectations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 BrianJ.MillerandPeterF.Buckley 5 OverviewofPharmacologicalTreatmentsandGuidelines. . . . . . . 65 SiobhanGeeandDavidTaylor 6 Clozapine:GoldStandardTreatmentforRefractory Schizophrenia:NoworNever?. . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 P.F.J.SchulteandJamesH.MacCabe 7 WhatCanWeDoIfClozapineFails?PharmacologicChoices andDifferentialOutcomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 DavidJ.CastleandNicholasKeks 8 TherapeuticBrainStimulationinTreatment-Resistant Schizophrenia..... ...... ...... ...... ..... ...... ...... .. 107 PeterB.Rosenquist,AnthonyO.Ahmed,andW.VaughnMcCall 9 CognitiveTherapiesforRefractorySchizophrenia. . . . . . . . . . . . . 121 AndrewWatson,MatteoCella,andTilWykes 10 CognitiveBehaviouralTherapyforPsychosis. . . . . . . . . . . . . . . . . 139 ElaineC.M.Hunter,LouiseC.Johns,JulianaOnwumere, andEmmanuellePeters vii viii Contents 11 VocationalRehabilitationforSevereMentalIllness. . . . . . . . . . . . 165 SusanR.McGurkandKimT.Mueser 12 PharmacogeneticsandTreatment-ResistantSchizophrenia. . . . . . 179 AdrianaFosterandPeterF.Buckley 13 FamilyInterventionsinPsychosis. . . . . . . . . . . . . . . . . . . . . . . . . . 195 JulianaOnwumere,ElaineHunter,andElizabethKuipers Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 1 Treatment-Refractory Schizophrenia: Definition and Assessment Derek K. Tracy and Sukhwinder S. Shergill Psychoticillnessesaffectbetween2and3.5%ofthepopulation(Peralaetal.2007) with schizophrenia accounting for 0.3–0.7 % (McGrath et al. 2008). The onset of schizophrenia is typically 3–4 years earlier in men, the incidence peaking at ages 21–25,withwomenshowingabimodaldistributionwithpeaksatboth25–30and perimenopausally(FalkenburgandTracy2014).Sincetheserendipitousdiscovery of chlorpromazine in the 1950s, the primary treatment of schizophrenia has been antipsychoticmedication.Theirintroductionrevolutionisedthecareofmillionsand heraldedaprocessofenormousdeinstitutionalisationandtheendoftheeraofthe asylum (Kirkby 2005). Nevertheless, it’s becoming clear that they do not benefit everyone and the burden of treatment refractory illness remains an enormous personal, clinical and societal problem. There are several inherent difficulties in managingthistreatmentrefractorypatientgroup,includingalackofconsensuson how to define the issue of refractory illness; uncertainty around which factors to give most attention to in the assessment; establishing treatment goals that are reasonable and rational; setting up a care plan when standard guidelines break down;andstandardisedmonitoringforclinicalchanges. It’snotcurrentlypossibletopredictthosepatientswhowillorwillnotrespond toantipsychoticmedication,andthereisincreasinginterestinthisareainorderto bettertarget ourdrugdevelopmentofnewcompounds andalsotoestablishbetter biomarkersforourexistingmedications.Reverseengineeringofantipsychoticdrug actions(CarlssonandLindqvist1963;Seemanetal.1975)ledtothedopaminergic D.K.Tracy OxleasNHSFoundationTrust,London,UK InstituteofPsychiatry,London,UK e-mail:[email protected] S.S.Shergill(*) NationalPsychosisUnitattheMaudsleyandBethlemHospitals,London,UK InstituteofPsychiatry,London,UK e-mail:[email protected] P.F.BuckleyandF.Gaughran(eds.),Treatment-RefractorySchizophrenia, 1 DOI10.1007/978-3-642-45257-4_1,#Springer-VerlagBerlinHeidelberg2014
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