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patients at ionale and rf intervenchosis in a 'atry 2OO2; f the initial lromal SynIidity. Am I g von Basis;). Springer: ;ing schizo3-764. s. Schizophr :rature. III. Ldwill they The useof conceptsin relationto early intervention in psychosis: a criticaldiscussion K Larsen The idea of early intervention in psychosis has emerged and developed rapidly during the past decade- a kind of 'movement' seemedto develop with the energetic ProfessorPatrick McGorry from Melbourne, Australia, as its initiator. Meetings of the International Early Psychosis Association (IEPA) are arranged regularly and early-detection servicesare evolving all over the world. The idea of early intervention has brought new concepts into the field of psychiatric discourse on psychosis, such as primary prevention, at-risk mental states,etc. This calls for analysisof the conceptsthat are being used. This chapter is largely basedon a review on conceptual and ethical problems related to early intervention and/or prevention of psychosis by Heinemaa and Larsen,l pubiished recently rn Current Opinion in Psychiatry.Some aspectswill be elaborated and a new concept (hypopsychosis)related to the description of possiblepresagesto psychosiswill be introduced. The discussionwill focus on basic conceptsthat we use and develop when we talk about early intervention in psychosisand some key conceptswill be discussedin more depth. These concepts are the brief limited intermittent psychotic states (BLIPS)and the idea of false positives. Early psychosis is often divided into phases such as the prodromai phase, the duration of untreatedpsychosis(DUP)and treatedpsychosis(Figure11.1). When talking about early detection, one could either focus on the reduction of DUP (secondary prevention), or try to intervene before the 92 Schizophrenia: Challengingthe Orthodox only one showed tra @ inary, on small samp question of whether . developing. When wor king wi problem is encountet that imply, with abso lllness onset Episode onset I End of episode Illness duration I Psychotic episode duration I I (Modifiecl Figure 17.1 Earlycourseof psychosis. fi'orttLttrsettTK et rrl. SchizophrBull 1996;22:241-256.2)ON,onsetof rtegotive symptotns; OP,rntsetof psychosis, positive symptorns;OS,onsetof psychoticsyndrorne; OT, onsetof treafinent;DUP,durationof psychosis. untreated problematic because develop what is pre' psychotic might be consideration that t expectedto have a hi and, despite recent e chosis and schizophr concepts are 'prepsy Many studies and m seemsdifficult to dis< onset of psychosisat the so-calledprodromal stage(primary prevention).In the early Treatment and Intervention in PsychosisStudy (TIPS)a reduction these concepts are t should one label the in DUP from 26 weeks (median) before any early-detectionstrategieswere developed(historicalcontrol sample 1993-94),to 4,5 weeks (median) was vention of psychosis achieved with the use of early-detectionstrategies(early-detectionsample), such as education campaignsand low-threshold detection teams.:JReceiving to take a close lool presagesto psychos developed some kinc early treatment was significantly correlatedwith fewer symptoms and better social functioning at the start of treatment and currently a I, 2, 5 and 10 cases? year follow-up of the sample is being carried out to study whether early detection has a lasting effect on outcome. this is a key concep 5 St at es( CAARM S)an In Stavanger,Norway, (the early-intervention site of TIPS) a clinic has been establishedfor those that have psychosis-likesymptoms, but do not fulfil the criteria for full-blown psychosisaccording to the TIPSinclusion criteria (which is equivalentto 'psychosis'accordingto DSM-IV, seediscussion ments describingpre later). At this early Treatment Of PrePsychosis(TOPP)clinic, we treat individuals without antipsychotic medications and it has been experiencedthat intensive psychotherapy might prevent development of psychosis. In the first 14 casesdetected during the first 2 yearswe found a transition rate to psychosisof about 40% within the first year. In the past 2 years two skilled psychologistshave been employed, who are treating these casesvery intensively with psychotherapy and out of the last 10 casesfollowed for 1 year, The concept'at-ris really be called 'at-ti not included, it is un used scale for desc Interview for Prodro SIPSincorporates mi GermanyTand the Bt prodromal statestha definitions are given Useof conceptsin earlyintervention in psychosis 93 only one showed transition to psychosis.These data are of course preliminary, on small samplesand must be interpreted with caution, but raise the question of whether medication is the only way to prevent psychosisfrom developing. When working with these possibly prepsychotic people a significant problem is encountered related to which conceptsone should use. Concepts that imply, with absolutenecessity,an upcoming transition to psychosisare problematic becauseif the preventive strategieswork, the patients will not develop what is prevented. Being stigmatized as possibly (probably?) prepsychotic might be harmful for some patients. It must be taken into consideration that people who fulfil criteria for prepsychosis must be expectedto have a higher rate of close relativeswith severemental disorders and, despite recent anti-stigma campaigns, the popular myths about psychosisand schizophreniaare still very pessimistic.aExamplesof such invalid concepts are'prepsychosis, pre-schizophreniaand prodromal symptoms'. Many studies and manuals are, however, still using these concepts and it seemsdifficult to discover better concepts and avoid misunderstandings.All these concepts are truly retrospective and should be avoided. How then should one label the people who are included in studies of primary prevention of psychosis?In order to come up with better alternativeswe need to take a close look at what clinical syndromes the different tentative presagesto psychosis consist of, i.e. are we treating people who have developed some kind of symptoms or are they non-symptomatic high risk cases? The concept 'at-risk mental state' was developedby the Melbourne group; this is a key concept in the Comprehensive Assessmentof At Risk Mental States(CAARMS)5and forms a conceptualbasisfor a number of other instruments describing prepsychosis.The problem with this term is that it should really be called 'at-risk of psychosismental state'. If the word 'psychosis'is not included, it is unclear what kind of risk is involved. The most frequently used scale for describing prepsychotic stages is probably the Structured Interview for Prodromal Syndromes (SIPS)developed by the PRIME group.n SIPSincorporates many of the ideas developed by the thorough studies in GermanyTand the Bonn Scaleof BasicSymptoms (BSABS).SIPSdefinesthree prodromal statesthat correspondwell to the syndromesin the CAARMSand definitions are given in Box 11.1. I II Challengingthe Orthodox 94 Schizophrenia: Box 1.1.L Structured Interview for Prodromal Syndromes (SIPS) criteria criteria for psychosis IV - the psychosisl for prodromal syndromes duration criteria wha (A) Brief intermittent psychotic syndrome Positivesymptomsat psychoticintensityare present,but they are not disorganizingor dangerousor do not lastfor at leastt hour per day at an averagefrequencyof 4 daysper week over 1 month. lf the psychoticintensity symptoms have never been presentat that frequency,but have begun in the past 3 monthsand are currentlypresentat leastseveralminutesa day at a frequencyof at leastonce per month, the criteriafor this prodromalsyndrome are met (B) Attenuated positive prodromal syndrome The prodromalor attenuatedpositivesymptomsarefound on scalesP'l-P5of the Scaleof prodromalsymptoms(SOPS).A scoreof 3,4, or 5 on any symptom scaledefinesthe prodromal levelof intensity.lf any of the symptoms havebegun in the pastyearor currentlyrate at leastone scalepoint higher comparedto 12 monthsago and occurat this levelat an averagefrequencyof at leastonce per week in the pastmonth, the criteriafor this prodromal syndromeare met (C) Genetic risk and deterioration syndrome spectrumdisorderand Consistsof a combinedgeneticriskfor a schizophrenic The geneticriskcriteriacan be met if the recentfunctionaldeterioration. patient has a first-degreerelativewith any psychoticdisorder(affectiveor nonaffective)and/or the patient meets DSM-lVschizotypalpersonalitydisorder criteria.Functionaldeteriorationis operationallydefinedas a 30oloor greater of Functioning(CAF)scoreduring the past drop in the GlobalAssessment month comparedwith 12 monthsago A c rit iq u eo f t h e c o n c e p t' b r ie fin te r m itte n t psychoticstate' Recent studies on primary prevention of psychosishave clearly found that few patients with the genetic high risk and recent psychosociaideterioration subtypesare detected,they simply do not seem to be treatment seeking.In my view, the group of brief intermittent psychotic statesshould not to be included at all as a possibleprodromal state. Both McGlashan and McGorry state that the brief psychosis subtype 'do not meet the DSM-IV duration chotic symPtomatolo grosslydisorganizedc information to make dictory information, t the criteria for any I these criteria, any PS should fall in this r detectedpsychosisan not need anY treatme tually wrong to cla sequenceof this crit necessarilyat a clinic dition, maybe in so presageto more sev stancesa Pre- or hYP on primary Preventio A new concep Since we regardthe I high risk grouP seem chosis, we are left w the attenu SIPS-scale; function as a diagn chopathology, but it severeearlier on, wh o ne t hat is m or e ad these casesis neede becaus hypopsychosls seekingand ill, and we understandhYPo into manifest PsYch some sort of treatme psychotherapYand ication might emerg in psychosis 95 in earlyintenvention Useof concepts criteriafor psychosis',but the most unspecific concept of psychosisin DSMIV - the psychosis Not Otherwise Specified (NOS) - does not give any duration criteria whatsoever.The criteria read: 'This category includes psychotic symptomatology (i.e. delusions, hallucinations, disorganizedspeech, grosslydisorganizedor catatonic behaviour) about which there is inadequate information to make a specific diagnosis or about which there is contradictory information, or disorderswith psychotic symptoms that do not meet the criteria for any specific psychotic disorder'.EThe way we understand thesecriteria, any psychotic condition even with extremely short duration, should fall in this category. Psychosis NOS thus comprises both earlydetectedpsychosisand possible'benign' forms of psychosisthat probably do not need any treatment at all. Under any circumstancesit would be conceptually wrong to classify them as prodromal or prepsychotic. The consequenceof this critique ought to be conceived at a conceptual and not necessarilyat a clinical level. BLIPSshould be understood as a psychotic condition, maybe in some instances as a benign subtype. BLIPS might be a presageto more severe(long-lasting) psychosis,but it is under no circumstancesa pre- or hypopsychotic state and should be excluded from studies on primary prevention of psychosis. A new concept- hypopsychosis Sincewe regard the BLIPSas a per definition psychotic state and the genetic high risk group seemsto be very rare in studiesof primary prevention of psychosis,we are left with only one group of possible prepsychoticsfrom the the attenuated positive symptom state.This concept is too long to SIPS-scale; function as a diagnosis, it is more a description of the underlying psychopathology, but it also seemsto imply that the symptoms have been mole severeearlier on, which is very often not the case.A more brief concept and one that is rnore adequately related to the clinical picture that we see in these casesis needed. I believe that a better concept for this condition is hypopsychosis becauseit emphasizesthe fact that these patients are treatment seekingand ili, and that we are dealing with a clinical condition, much like we understandhypomania as relatedto mania. Hypopsychosismight develop into manifest psychosisor it might vanish in time or as a consequenceof some sort of treatment. In our clinic hypopsychosisis treatedwith supportive psychotherapy and rehabilitation, but in other studies antipsychotic medication might emergeas effective.Even a concept such as 'antipsychotics'is a 96 Schizophrenia: Challengingthe Orthodox construct developed to label medication that is effective in the treatment of psychosis. If research shows that antipsychotics are effective also for hypopsychosis it may be better to label these drugs neuromodulators,taking this effect into consideration. Ongoing studies with sound scientific designs (randomized and double blind) will reveal more about the effect of neuromodulators such as antipsychotics on hypopsychosis; only with time will we be able to iudge what the best treatment will be. One advantage with the concept of hypopsychosis is that it can be understood as a condition that might need treatment in itself - it is not a condition that necessarily will clinic, McGorry's grouP) an group), but sound studies art lands, Germany and in Scan that there is a thorough dis related to primarY Preventio of treatment and detection it The labelling of non-PsYch 'preschizophrenic'or'at risk develop into something more severe. Patients who are treated for hypopsy- be borne in mind that the dii believe that the introduction chosis can conceptualize and understand the treatment given with the specific aim of reducing the symptoms that were present and not only in order forward somewhat; hYPoPs such as SIPS)that needstreat to prevent something in the future. Even patients who never develop a more serious condition can receive treatment within this paradigm. cases)can be a Presageto I having early PsYchosis,but i similar to hypomania, a cot The prob i e mw i t h ' f a l s ep o s i tive s' ceptual controversY.PerhaP does not always require ther Another concept that is often used in a confusing manner in discussionson prevention of psychosis is the 'false positives'. False positives are used to in studies on Primary Pre worried that their problems disabling. We arguethat BLI characterizethose casesthat fulfil criteria for some tentative prepsychotic condition, but never develop (or would have developed)psychosis.Normally false positivenessmeans casesin which a screening test gives a false suspicion of the underlying disorderwe are screeningfor. An example would be a blood test for some infection, but when we carry out more thorough tests, we have a negative result. Whether a condition (hypopsychosis)develops into another disorder (psychosis)has nothing to do with false positives,but rather to which degree the first condition is a presageto the second (predictive power). Falsepositive casesof hypopsychosiswould be casesin which a positive screening test for hypopsychosis proved to be false when we carried out a more complete assessment. Co n clu d i ngremark s In general the field of research regarding primary prevention of psychosis seems to be making significant progress. There are several ongoing and promising studies from which we expect to learn more about whether it really is possible to detect and treat people who are at the edge of developing psychosis.The most promising studiesare being carriedout in Australia(the pACE condition and not as PrePS use of other keY concePtss general.Finally, we believet. more valid descriPtionof hY to bring more claritY to this References Heinemaa M, LarsenTK, nosis and intervention. Ct 2. Larsen TK, McGlashan TI Bull parameters.SchizoPhr 3. LarsenTK, McGlashanTH first episodeof PsYchosis chiatryZOOI;L58:1917-19 4. Larsen TK, OPiordsmoen conceptualand ethical co 5. McGorry PD, Preventives chiatrySuPPI1998; 172:76. Miller TJ, McGlashan TH drome for schizoPhren 1. Useof conceptsin earlyintervention in psychosis 92 clinic, McGorry's group) and in the USA (the PRIME clinic, McGlashan's group), but sound studies are also being carried out in the UK, in the Netherlands, Germany and in Scandinavian countries. It is, however, very important that there is a thorough discussion of both ethical and conceptual problems related to primary prevention of psychosis in order to avoid the establishrnent of treatment and detection initiatives that are not ethically or clinically sound. The labelling of non-psychotic people as 'possibly psychotic', 'prepsychotic', 'preschizophrenic' or 'at risk of developing psychosis' is controversial. It should be borne in mind that the diagnosis should be tor the benefit of the people. We believe that the introduction of the concept 'hypopsychosis' can bring the field forward somewhat; hypopsychosis is a clinical condition (defined in manuals such as SIPS)that needs treatment, which often (probably in almost 507o of the cases) can be a presage to psychosis. The concept does not label people as having early psychosis, but a weak form of psychosis. Hypopsychosis is much similar to hypomarria, a concept that has not created much clinical or conceptual controversy. Perhaps hypopsychosis is a rather benign condition that does not always require therapy. People with hypopsychosis who are included in studies on primary prevention should be both treatment seeking and worried that their problems might develop into something more severe and disabling. We argue that BLIPS should be understood and treated as a psychotic condition and not as prepsychosis, and there should be a more unambiguous use of other key concepts such as false positives and primary prevention in general. Finally, we believe that ongoing research soon will be able to develop a more valid description of hypopsychosis and we support any attempt that aims to bring more clarity to this promising field of clinical research. References 1. Heinemaa M, LarsenTK, Psychosis:conceptual and ethical aspectsof early diagnosisand intervention.Curr OpinPsychiatry 2002;15:533-541. 2. Larsen TK, McGlashan TH, Moe LC, First episode schizophrenia.I Early course parameters Bull 7996;22:247-256. . Scltizophr 3. LarsenTK, McGiashanTH, Johannessen JO et al, Shortenedduration of untreated Ilrst episodeof psychosis:changesin patient characteristicsat treatment.Anr I Psychiatry2OO7;158:1917-1919. 4. LarsenTK, Opjordsmoen S, Early identification and treatment of schizophrenia: conceptualand ethical considerations.Psychiatry1996; 59:371-380. 5. McGorry PD, Preventivestrategiesin early psychosis:verging on reality. Br I Psychiatry&tppl 1998;772:7-2. 6. Miller '[, McGlashanTH, RosenJL et al, Prospectivediagnosisof the initial prodrome for schizophrenia based on the Structured lnterview for Prodromal 98 Schizophrenia:Challenging the Orthodox 7' B' Syndromes: preliminary evidence of interrater reliability and predictive validity. Arn I Psychiatry 2OO2; 159:863-865. Huber G, Gross G, The concept of basic symptoms in schizophrenic and schizoaffective psychoses. Recenti prog Med 1989; gO:646_652. American Psychiatric Association. DSM-lv, Diagnostic antl Stntistical Manual of Mental Disorclers' (4th edn). American Psychiatric Association: Washington, DC, 7994. ls the re duratio psycho a resul deficits A cornerstoneargument have investigatedthe lin prognosis and repofted outcome than those wit treatment.l'2The rationa a favourable impact on existence of a causallir lished,asthesefindings onset of psychosisand fi to the other characteri seeking,such as poor prl also independently pred and poor outcomemay e Characteristic untreatedpsych The first question is to naturalistic settings.T