An Evolving System of Early Detection and Optimal Management

VOL. 22, NO. 2, 1996 EPPIC: An EvolvingSystem of Early Detectionand Optimal Management

by Patrick D. McGorry,Jane Edwards, CathrlneMlhalopoulos, Susan M.Harrlgan, and Henry J.Jackson

Abstract

Early intervention at the onset ofpsychotic disorders is a highlyattractive theoretical notion thatis receiving increasing interna-tional interest In practical terms,it amounts to first decidingwhen a psychotic disorder canbe said to have commenced andthen offering potentially effectivetreatment at the earliest possiblepoint. A second element involvesensuring that this interventionconstitutes best practice for thisphase of illness and is notmerely the translation of stand-ard treatments developed for la-ter stages and the more per-sistently ill subgroups of thedisorder. Furthermore, it meansensuring that this best practicemodel is actually delivered topatients and families. The rela-tive importance of these elementsin relation to outcome has notyet been established. This articleoutlines a framework for preven-tive intervention in early psy-chosis, based on more than adecade of experience initiallygained within a first-generationmodel. This experience has beenfollowed, after a prolonged ges-tation, by the birth of the EarlyPsychosis Prevention and Inter-vention Centre (EPPIC), a com-prehensive "real-world" model ofcare targeting the multiple clini-cal foci underpinning the preven-tive task. Data are reported to il-lustrate the topography andimpact of delay in treatment inour regional setting, and the re-sults of an initial evaluation ofthe EPPIC model are presented.The latter demonstrate a signifi-cant improvement in sympto-matic and functional outcomewhen the second-generation

model is contrasted with thefirst. The implications of thesefindings and future develop-ments are discussed.

Schizophrenia Bulletin,22(2):305-326, 1996.

Very early schizophrenia stillconstitutes a relatively unex-plored territory. Entry into thisterritory calls for new ideas onthe social problems involved inbringing the early schizophrenicunder treatment, or where thetreatment should be carried outand in what it should consist.[Cameron 1938, p. 577]

These words, penned nearly sixdecades ago before the availabilityof neuroleptic treatment, still pro-vide a surprisingly accurate de-scription of the present status ofclinical care for young people withan emergent psychotic disorder.They also succinctly state some ofthe key issues on which we mustachieve consensus if we are toprovide timely and optimal treat-ment for new generations ofyoung people and their familiesaffected by this group of pervasiveand persistent disorders. Cameronand his contemporary Harry StackSullivan were prominent initial ex-plorers of the territory of earlypsychosis. After an extended dor-mant period, a second generationof explorers has emerged, foundcommon ground, and establishedsubstantial momentum. This articledescribes our own endeavors overthe past decade to map the terri-

Reprint requests should be sent toDr. P.D. McGorry, Director, Early Psy-chosis Prevention and InterventionCentre (EPPIC), Locked Bag 10,35 Poplar Rd., Parkville, Victoria 3052,Australia.

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tory, to intervene earlier, and toprovide better and more humaneforms of treatment and care.

Foundations of the EarlyPsychosis and InterventionCentre (EPPIC)

In setting out some of the princi-ples and frameworks underpinningour clinical approach, it is impor-tant to note mat these haveevolved over time as part of acontinuous learning process. Wehave endeavored to make themexplicit, both as a distillate of ourclinical and research experienceand as a critique of concepts andpractice in the wider field of psy-chotic disorders. This may be use-ful in orienting the reader to thelater sections of the article.

The Preventive Framework.Prevention has been an elusivegoal in psychotic disorders. Argua-bly, this is because the focus forour preventive thinking has beenmore advanced than our knowl-edge base, and hence overly am-bitious. We still have only a vaguesense of the underlying risk fac-tors and neurobiology of the psy-choses, a prerequisite for primaryprevention. The tantalizing ideathat we may be on the verge of aneuroscientific breakthrough thatcould support primary preventivestrategies may have inadvertentlycontributed to paralysis in second-ary prevention. However, second-ary prevention is highly feasible,even with current levels of knowl-edge (McGorry 1992; McGorry andSingh 1995).

An examination of the longitudi-nal course of psychotic disordersand the prevailing standard ofclinical care illustrates the potential

scope for secondary prevention(Birchwood and MacMillan 1993).First, prolonged delays before thefirst effective treatment for psy-chosis are common 0ohnstone etal. 1986; Loebel et al. 1992; Beiseret al. 1993), delays that are associ-ated with slower and less com-plete recovery (e.g., Helgason 1990;Loebel et al. 1992). Second, thecritical period for vulnerability torelapse and the development ofdisability and handicap is duringthe early years after onset (Birch-wood and MacMillan 1993). Itseems likely that these disordersare at their most severe in a bio-logical sense in their early stages,and their disruptive and disablingeffects are enhanced by the ex-quisitely sensitive developmentalphase during which they manifest(Sullivan 1927/1994; Wyatt 1991;McGorry 1992). If this is true,there may be a particularly toxicinteraction between delay in treat-ment and the critical period,especially in those who ultimatelymeet criteria for schizophrenia,where treatment delays are moreprolonged (McGorry and Singh1995). This would mean that moreof the critical period would elapsebefore effective treatment, and in-deed more psychosocial decline isapparent in this phase of schizo-phrenia than in other first-episodepatients (Jones et al. 1993), a pos-sible contributor to greater subse-quent disability in people with thisdisorder. Finally, for the portion ofthe critical period that follows en-try to treatment, there is the issueof the quality, range, and intensityof the treatment provided. Al-though first-episode psychosis is ahighly treatment-responsive prob-lem (Lieberman et al. 1993), ourearly experiences with this groupof patients highlighted both the

crude and insensitive ways inwhich standard treatments weredelivered to young people duringtheir first contact with psychiatricservices and the significant gaps inexpertise and resources (McGorry1992). While some of these gapsreflected general deficiencies in themanagement of psychotic illness—including the use of excessivedoses of neuroleptics and a varietyof other iatrogenic influences—others were related to the need todevelop either age- and phase-specific variants of existing clinicalapproaches or completely novelforms of intervention. In otherwords, best-practice treatment forlater stages of the disorder and formore persistently ill and disabledsubgroups may not constitute bestpractice for early psychosis. Insummary, a realistic secondarypreventive approach would involvestrategies that first reduce the du-ration of untreated psychosis andsecond optimize the managementof the disorder during the earlyyears after detection. Such an ap-proach could be expected to resultin a more cost-effective service foryoung people at this stage of ill-ness (Moscarelli et al. 1991).

The Conceptual Framework. Adetailed critique has been providedelsewhere of the inadequacies ofthe neo-Kraepelinian diagnosticmodel in the setting of early psy-chosis (McGorry et al. 1990a;McGorry 19912>; McGorry 1995a),however, the issues will be brieflysummarized as follows.

The neo-Kraepelinian model isderived from a relatively earlystage of Kraepelin's thinking andit is curious that this stage in par-ticular has been so tenaciously re-tained and more recently revived,despite serious criticism (Arieti

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1974; Crow 1986; Boyle 1990; Ben-tall 1992). The syndromes of psy-chosis have been the subject ofendless multivariate analysis, andthe current consensus suggests thatthere are about five major syn-dromes (Liddle et al. 1994). Noneof these syndromes is unique toany of the major subcategories ofpsychotic disorder, and comor-bidity is the rule rather than theexception, especially in early psy-chosis. Treatment is by no meansdisorder-specific, and the capacityof diagnostic subcategories—suchas schizophrenia—to predict courseand outcome independently ofother variables—such as gender orpremorbid functioning—in the in-dividual case is relatively weak.The more specific fundamentalflaw with the neo-Kraepelinianversion of schizophrenia is, ofcourse, the continued blending ofsyndromal diagnosis with courseand duration criteria, using the lat-ter as a proxy, validating DSM-1V(American Psychiatric Association1994) criterion. This is a particularproblem in early psychosis, sincemost of the course of the illnesshas yet to unfold, and relation-ships between symptoms and func-tioning are fluid, not fixed. Otherfactors that make the model un-wieldy and unhelpful at this phaseof illness include diagnostic in-stability (Fennig et al. 1994; Mc-Gorry 1994; Woerner et al. 1995),high comorbidity (Strakowski et al.1993; McGorry 1994), and the re-versible nature of negative symp-toms (McGlashan and Fenton1992), with correspondingly lowlevels of primary negative symp-toms and the deficit state (May-erhoff et al. 1994). The significanceof symptoms in first-episode sam-ples may therefore be differentfrom that in selected chronic sub-

samples (McGlashan and Fenton1992). The likelihood, then, is thatthe clinician's illusion (Cohen andCohen 1984) distorts perceptions inmore heterogeneous samples offunctional psychosis, such as first-episode patients.

This suggests that the more gen-eral term "psychosis" would bemore clinically useful in first-episode and early psychosis sam-ples, at least for a period beyondthe emergence of a psychotic dis-order (McGorry 1995a). Such anapproach does not in any waydeemphasize that the patient issuffering from a usually pervasiveand potentially serious psychiatricdisorder. This stance derives somesupport from the research arena,where most groups studying first-episode samples have tended tofocus on first-episode psychosisrather than first-episode schizo-phrenia. Clearly, it remains desir-able and useful to apply opera-tional definitions of currentsubcategories of psychotic disorder,both for research and communica-tion purposes and to interact effec-tively with a range of other serv-ice agencies that are more familiarand comfortable with these terms.A more flexible course-basedmodel, which we have found use-ful in early psychosis, is brieflydescribed below.

Psychosis is a global and essen-tially simple syndrome, definednarrowly by the presence of clear-cut delusions or hallucinations ormore broadly by including markedthought disorder and severe cata-tonic features. It may occur in as-sociation with major depression,mania, or primary negative or def-icit symptoms; it is the differentcombinations of these syndromeswith psychosis that give rise toour categories of psychotic disor-

der. Alternatively, one could definepsychosis narrowly as the presenceof delusions and hallucinations, al-lowing the disorganization syn-drome (Liddle 1987) and catatoniato be included among the associ-ated syndromes. Course has beenembedded as a variable in con-structing the existing classificationsystem, and it may yet be helpfulin designing a treatment-sensitiveclassification (McGorry 1995b). Thedimension of course needs to bepulled apart from syndromes,however, and the most logical wayto do this is to draw on the con-cept of staging as used in clinicalmedicine (Fava and Kellner 1993).This notion of staging, with dif-ferential transition rates from onestage to the next, has been elabo-rated as a prevention strategy forthe early natural history of disor-ders (Eaton et al. 1995; Yung et al.1996, this issue). Here we extendit to the postonset phase.

The model shown in figure 1 isa matrix of phase of illness, pat-tern of syndromes present duringand between episodes of relapse,and the associated levels of dis-ability and handicap. A key dis-tinction is made between thephase of early psychosis—precursors, prodrome, and firstpsychotic episode—and the phaseof "prolonged psychosis" (Harding1992, personal communication). Anintermediate phase can be identi-fied in between the first episodeand the period of prolonged psy-chosis, which has been termed the"critical period" (Birchwood andMacMillan 1993) because of its re-lationship to the timing of the de-velopment of disability. The transi-tions from one phase to another—that is, from precursors or pro-drome to the first psychoticepisode, from the first episode to

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Figure 1. Phase-oriented classification of psychosis

IMPAIRMBtfT(syndromes)

Earty Psychosis

ProdromeFirst

EpisodePsychosis

+

Critical Period

Persistent Relapse

Prolonged Psychosis

Persistent Relapse

None

PS

MS

DS

NS

COM

PD

None

DISABIU- Inter-TY/Handicap mttteot

Sus-tained

PS » positive symptoms; MS = manic symptoms; DS » depressive symptoms; NS • negativesymptoms; COM = other Axis I comorbtdlty, e.g., panic, post-traumatic stress disorder,substance abuse; PD = personality disorder.

the critical period, and from thecritical period to prolongedpsychosis—are key nodal proc-esses, with only a proportion ofpeople progressing across eachnode. Better understanding of thefactors influencing such transitions,and hence improved predictivepower, would be extremely useful.Even now, these nodes and the in-tervening phases seem most im-portant for planning preventivetreatment strategies. A fuller de-scription of this model can befound elsewhere (McGorry 1995b).

The Developmental Frame-work. The period of maximum

risk for the onset of a psychoticdisorder, particularly in males, isthe late adolescent or early adultstage (Kosky and Hardy 1992).This is a critical developmentalphase in the life cycle of the indi-vidual and of the family of origin,one which involves the consolida-tion of identity, the process ofseparation and individuation fromparents, crucial educational andvocational steps, and constructionof an independent peer group, allof which may be important for along time. The onset of even a rel-atively mild psychiatric disordercan permanently derail and trun-cate educational attainment (Kes-

sler et al. 1995). When a majorpsychiatric disorder, such as apsychosis, strikes in this life stage,there is a potential for "personaldisaster" (Raphael 1986) and dis-ruption to all of the above de-velopmental lines even with goodtreatment response. Identity forma-tion may be seriously clouded andundermined; the family structureand evolution may be stressed andstunted; the education and careermay be cut off at the knees, and,in a context of high youth unem-ployment, never recover; and thenotoriously evanescent peer groupmay move on, leaving the youngperson struggling to recover andfloundering badly. Adult psychiat-ric services designed for and morefamiliar with older cohorts ofmore disabled patients tend tooverlook this key perspective.

A related and emergent frame-work is derived from the con-sumer perspective, which hasarisen in recent years for a varietyof reasons, but partly as a re-sponse to the disempowerment in-herent in the role of the psychiat-ric patient in contemporary societyand reflected in the traditionalpractices of mental health agencies.The consumer perspective is highlycongruent with the clinical objec-tive of ultimate illness self-management, a realistic aim in themajority of people with psychoticdisorders (Strauss et al. 1987).

Models of Early Intervention

First-Generation Models of Inter-vention: The Aubrey Lewis Unitand the Recovery Program. In1984 a clinical and research focuson first-episode and recent-onsetpsychosis began at Royal ParkHospital, then a 179-bed psychiat-ric hospital serving the inner city

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and the northern and western sub-urbs of Melbourne, with a catch-ment population of approximately485,000 adults. The focal point ofthe research program, the AubreyLewis Clinical Research Unit,opened as a 10-bed acute inpatientward in October 1984 (McGorry1985). The unit's early clinical ex-perience with the first-episodegroup led to a better understand-ing of the particular clinical needsof these patients, the limitations ofstandard care, and the possibilitiesfor a broader, more preventive ap-proach. During 1986 an oppor-tunity arose to expand the bedsand clinical resources of the pro-gram by refocusing the work of ahospital rehabilitation unit. This"recovery" program set out to ad-dress the comprehensive psychoso-cial needs of patients recoveringfrom an episode of psychosis inthe recent-onset group (either first-episode or psychotic relapse occur-ring within 3 years of first onsetof psychotic features). The pro-gram was closely linked with theAubrey Lewis Unit, which carriedout the initial assessment andacute phase treatment; patientsmoved to the recovery unit for theremainder of their hospital stay.Eventually, a common 21-bed unit,into which both programs weremerged, was opened in 1990 bySir Michael Shepherd (Copolov1991). The philosophy and opera-tion of these early models of carehave been described in detail else-where (McGorry 1985, 1992;Copolov et al. 1989; McGorry etal. 1989, 1990a; Edwards et al.1994).

The EPPIC: A Second-GenerationModel of Care. EPPIC com-menced operation in October 1992,seeking to provide a comprehen-

sive community-based service toolder adolescents and young adultsexperiencing the first onset of apsychotic illness and to provideongoing care through the criticalperiod. The center's comprehensiveaims were to address and embraceearly detection, to prevent second-ary morbidity, and maintain socialand occupational functioning dur-ing the early "critical period,"namely the initial 2 years after en-try into treatment. The initial blue-print comprised six clinical com-ponents, linked to an extensiveprogram of research that has beena critical catalyst in developing theprogram (McGorry 1993; Edwardset al. 1994). The initial configura-tion of the program and its com-ponents will be described brieflyhere, since this model was in op-eration when the evaluation sam-ple (see below) was treated; how-ever, recent modifications will bereferred to as well. A fuller ac-count is provided in McGorry andJackson (in press).

The second-generation modelhad two fundamental aims: first,to identify patients at the earlieststage from onset of psychosis, andsecond, to provide intensive phase-specific treatment for up to 2years thereafter. A larger catch-ment area was necessary to justifya full range of program compo-nents, including an inpatient unitand a separate mobile team, andpart of the rationale for the serv-ice also included a focus on youthand emphasized the epidemiologyof psychotic disorders, particularlythe patterns of age at onset. Thus,the upper age limit was reducedfrom 45 to 30 years, but the otherfirst-generation inclusion criteriawere retained (see below). Thecatchment area was virtually dou-bled in size to approximately

800,000 people, covering the west-ern metropolitan region ofMelbourne, an area served by twopublic psychiatric hospitals andfive community mental health cen-ters. Census data indicated that in1991 the number of people withinEPPIC s catchment area and agerange was 208,104 (Australian Bu-reau of Statistics 1991), a popula-tion base that we expected toyield about 200 new cases of psy-chosis each year; the actual yieldhas been approximately 250 eachyear. Important demographic fea-tures of the region include a largeproportion of people who werebom overseas or whose parentswere born overseas and a highproportion from the lowest socio-economic status groups.

Program components. An EarlyPsychosis Assessment Team(EPAT) was established as amobile team to serve as the soleentry point to EPPIC. EPAT hashad an extensive community de-velopment task in addition to itsassessment role, and thus it aimedto tackle the issues of delayedcase detection and impeded accessto appropriate treatment in a num-ber of complementary ways.Through networking and carefullytargeted community education ac-tivities, EPAT sought to raise com-munity awareness of psychosis inyoung people and promote recog-nition and early referral. In addi-tion, an awareness that the onsetof a psychotic illness and psychiat-ric treatment may be traumatic forboth the individual and the familyled EPAT members to minimizethe stress involved in what islikely to be the patient's and fam-ily's first contact with psychiatricservices. This approach includesproviding information and supportat each stage of the assessment

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phase; being available to conductassessments in the least threaten-ing environment, for example, inthe home, school, or local doctor'soffice; and responding flexibly toeach situation. In some cases, as-sessments are conducted over anextended period of time by thesame team members in order tofoster the development of trust tofacilitate the assessment and treat-ment process. The twin goals ofreducing treatment delay whileavoiding coercive intervention andoverreaction to nonurgent situa-tions have at times been in con-flict. Balancing these objectives hasrequired a measure of skill andfine judgment.

During the first 12 months ofoperation EPAT responded to 460referrals, of which 273 wereclinically assessed and 183 wereaccepted into the EPPIC program.In the second 12 months, thesefigures increased, with EPAT re-ceiving 496 referrals, directly as-sessing 314, and accepting 215 ofthese young people into the EPPICprogram. Other cases entered theprogram through direct admissionto the inpatient unit after hours(approximately 70 patients in thefirst 12 months, 40 in the second12 months); EPAT assumed a 24-hour case-finding function in thethird year of the program. Fortypercent of the assessments tookplace at the young person's ownhome, and 21 percent at a non-psychiatric services agency such asa schooL counseling service, orgeneral practitioner's office.

Evaluation of the referral sourcesreflects the effectiveness of com-munity education and networking.In the first 6 months of operation49.8 percent of the referrals camefrom nonpsychiatric sources. Thishad increased to 69.2 percent in

the second 6 months. Family andfriends were the source of 9.8 per-cent of referrals in the first 6months, and this had increased to24.5 percent in the second 6months. The mean response timefor urgent referrals to EPAT was68 minutes in the first 12 months,reflecting EPAT's capacity to re-spond rapidly to potentialemergency situations. The averagetime to reach an assessment underthese circumstances reflects thelarge geographical area covered,with some suburbs lying over anhour's drive away from EPATsbase. The mean response time tononurgent referrals was 3.1 days,reflecting a desire to arrange as-sessments at a time convenient forthe young person and his or herfamily. Of those young people as-sessed by EPAT, 34 percent wereinitially admitted as inpatients, 31percent managed as outpatients,and the remainder were not con-sidered appropriate for the EPPICprogram and were either referredto a more appropriate service orwere subject to further assessmentand monitoring in selected "doubt-ful" cases. As part of EPAT's ob-jective to minimize the trauma as-sociated with initial psychiatriccontact, data on police involvementwith transporting a young personto the hospital were also collected.Police transport was required inonly 8.5 percent of all involuntaryadmissions.

Second, the outpatient case man-agement system, a therapist casemanager model, has become thecenterpiece of the second-generation model. Case managersare assigned at entry, and all as-pects of treatment are provided,linked, or accessed through thecase manager. This model safe-guards the continuity of care,

which is a precious commodityand difficult to achieve. A preven-tive, multidisciplinary approach hasbeen used to develop and docu-ment case management skills spe-cific to this population and phase.EPPIC has a steady caseload ofapproximately 300 active patients,with 20 new cases accepted eachmonth. Full-time case managerscarry individual caseloads of ap-proximately 40 patients, and eachpatient also sees a psychiatrist orsenior resident regularly.

A third program component, theinpatient unit, focuses on symptomreduction and containment. Oncethe indications for inpatient careare no longer met, the unit facili-tates rapid transition to the outpa-tient case management service,with mobile support if required.With the immediate assignment ofthe case manager at program en-try, longer-term psychosocial goalscan be identified early in the ini-tial acute phase. Staff memberswork across the different programcomponents to maintain continuityof care through readmissions andrelapses. The inpatient unit, orig-inally 21 beds, has recently beenreduced to 14 beds, and a mobilehome treatment service has as-sumed a bridging role to enablethose patients with adequate fam-ily support and low risk of self-harm or violence to avoid the dis-ruption of hospitalization. Thiscomponent, influenced by genericchanges in Australian psychiatry,has been blended with EPAT toform the Early Psychosis Assess-ment and Community TreatmentTeam (EPACT) and has enabledthe length of stay to be reducedfrom around 25 days to 12 days.Low doses of neuroleptics arestandard practice in the acutephase, and disturbed behavior is

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managed by close nursing supervi-sion; use of benzodiazepines andlithium, as "neuroleptic-sparing"agents; and minimal seclusion inan otherwise open environment.

The day program provides arange of group and individual ex-periences, and people axe referredduring the recovery phase of theirinitial psychotic episode. A tailoredprogram is derived from thechoices expressed by the partici-pants, who are expected to helpdraft and regularly review theirown individual programs. The pro-gram is a loosely linked set ofopen groups, a structure that en-ables a larger population (approx-imately 50 at all times) to be in-cluded, with a balance betweencohesion and flexibility. The dayprogram is based in a five-roomhouse, which provides a securebase although many of the ac-tivities actually take place in com-munity settings. All involvement isseen as time-limited, with partici-pants setting goals about (andworking toward) rejoining main-stream society—either where theyleft it or at a suitable new stageand place. Our data indicate thatmost participants have returned toeducation, work, or to other voca-tional rehabilitation programs. Oth-ers have maintained their func-tional level during contact andavoided the deterioration thatmight well have occurred other-wise (Francey et al. 1995).

Family work is another compo-nent of the program. The criticalrole of families and caretakers insupporting a young personthrough the first psychotic episodeis emphasized, and every effort ismade to include families in thetreatment process, since they arealso in crisis and require interven-tion. The needs of families for cri-

sis support and practical educationabout psychosis are addressedthrough multifamily group inter-ventions and individual sessionswith families with support from aspecialist family worker. Thesefamilies have little knowledge ofor experience with serious mentalillness, yet a significant burden ofcare is placed on them. Given thislevel of adaptive stress, most fam-ilies will find it difficult to cope,and dysfunctional patterns mayemerge or, if previously present,become exaggerated. Practical ad-vice and support, combined withthe family worker's family therapyskills—if used in conjunction withan illness model that avoids anysuggestion of blaming the family—can be invaluable.

Finally, the psychological chal-lenges inherent in recovering froma psychotic illness are addressedthrough cognitively oriented psy-chotherapy for early psychosis(COPE; Jackson et al., in press).This intervention aims to helpeach person adapt to the onset ofthe psychotic illness and its effectson his or her self-concept, identitydevelopment, and self-esteem.COPE also seeks to treat second-ary or comorbid disorders (Mc-Gorry et al. 1991) that may de-velop in the recovery phase of theinitial psychotic episode.

Further developments. Addi-tional components have been de-veloped to address special diffi-culties that have become apparentsince the evaluation sample de-scribed below was recruited andtreated. These subprograms andemerging models, described else-where (McGorry and Jackson, inpress), include accommodation(Pennell et al. 1995); a TreatmentResistance Early Assessment Team(TREAT) and Systematic Treatment

of Persistent Positive Symptoms(STOPP; Edwards et al. 1995); Per-sonal Assistance and Crisis Evalua-tion (PACE; Yung et al. 1996, thisissue); general practitioner liaison;comorbid substance abuse; voca-tional rehabilitation; suicide pre-vention; and comorbid personalitydisorder.

In summary, the focus placed onearly detection and intensive earlytreatment of emergent psychosis isdesigned to limit the damage topersonal identity, social networks,and role-functioning caused by theunderlying illness. The array ofservices offered to promote recov-ery and adaptation is aimed at re-ducing or delaying relapse andavoiding the development of sec-ondary consequences of having ex-perienced a psychotic episode. Theremainder of this article presents arange of data illustrating the pat-terns of onset of psychosis in ourregion and the impact of the serv-ice developments on delay andoutcome.

Scope for Earlier Detectionin Melbourne: Charting theLandscape

Patterns of delay and impededcare similar to those found else-where have been identified in ourown region. During the period1989-92, we conducted a prospec-tive followup study of 200 first-episode cases; these were carefullyassessed during the acute phaseand then followed for 12 monthsafter recovery at the 3- and 12-month time points. One aim ofthis study was to examine the pat-tern of delay and its impact onoutcome. Our first-generation clini-cal program was already relativelywell known as a specialized inpa-

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tient agency in the local servicesystem, able to access and treatthe overwhelming majority ofcases of first-episode psychosispresenting for inpatient care atRoyal Park Hospital from a strictlydefined catchment area (see be-low). Some cases from the catch-ment area may have receivedtreatment in private facilities orgeneral hospitals; however, theseagencies nearly always referredsuch cases to our unit for initialinpatient care, and we monitoredthem during the study to cross-check whether such patients werestill being referred. Nevertheless,some eligible cases may have beenmissed (Castle et al. 1994). Ap-proximately 75 percent of thoseeligible for the study (absence oforganic factors, poor English, andmental retardation; age 16-45 atonset; first treated episode of psy-chosis) participated, and the twogroups were not significantly dif-ferent on gender, education, mari-tal status, and country of birth.The nonparticipants, however,were nearly 5 years older on aver-age, had a significantly shorter du-ration of initial hospital stay, andmay have had more affective psy-chosis. However, the only diag-noses available for the latter groupwere nonoperan'onal hospital diag-noses of uncertain reliability andvalidity.

For the total sample of 200, themean age was 25.2 years; therewere 122 males and 78 females; 77percent of the sample had not yetmarried; and less than 20 percenthad begun tertiary education. TheDSM-HI-R (American PsychiatricAssociation 1987) diagnostic dis-tribution was schizophrenia 30.5percent; schizophreniform 24.0 per-cent; schizoaffective 10.0 percent;delusional disorder 6.5 percent; bi-

polar disorder with psychotic fea-tures 13.0 percent; major depres-sion with psychotic features 8.5percent; brief reactive psychosis 0.5percent; induced psychosis 0.5 per-cent; and psychotic disorder nototherwise specified 6.5 percent.Followup rates were 83.5 percentat 3 months and 70.0 percent at12 months; apart from a slight ex-cess of delusional disorder cases inthose lost to followup, there wereno significant differences betweensubjects who participated in fol-lowup and those who did not ona range of sociodemographic andclinical variables, including diag-nosis, duration of untreated psy-chosis, and duration of psychoticsymptoms in the initial episode.

The Topography of Delay. Theduration of the prodromal phase,the duration of untreated psy-chosis, and the level of premorbidfunctioning were carefully assessedusing the Royal Park Multidiag-nostic Instrument for Psychosis(McGorry et al. 1990b, 1990c) andthe Premorbid Adjustment Scale(PAS; Cannon-Spoor et al. 1982).This involved systematically inter-viewing the subjects and inform-ants and carefully mapping theonset of disorder. This time-consuming methodology was orig-inally developed for a study of therelationship between duration ofillness and the complexity of theclinical features in first-episodepsychosis (McGorry 1991a, 1994).We distinguished three phases:premorbid, prodromal, and psy-chotic, each of which was opera-tionally defined.

The data reveal a skewed dis-tribution with the majority ofcases, especially in the non-schizophrenia groups experiencingrelatively short delays, seen most

clearly in the median figures. Inthe schizophrenia group, thelonger delays are partly artifacrualbecause of the influence of the6-month criterion (particularly incontrast to the schizophreniformgroup). But the delays also seemto be related to other factors, pos-sibly the difficulty in recognizingthe emergent frankly psychotic fea-tures in the context of insidiousonset. Table 1 reports the data infull, illustrating a highly significantdifference in duration of untreatedpsychosis between the schizo-phrenia-only group and the othertwo groups (p < 0.0001). Durationof prodrome was also significantlylonger in the schizophrenia-onlygroup than in the other two (p <0.0001) and significantly shorter inthe schizophreniform-only groupthan in the other two, the latterbeing a largely artifactual result.The prodromal period was nearly3 times longer in the schizophreniagroup than in the nonschizo-phrenia group, and a higher pro-portion of cases manifested a pro-dromal phase (88.1% vs. 56.7%).The greatest scope overall for re-ducing delays seemed to be in thesignificant subsample of "outliers,"which produced large standarddeviations (SDs) on durationvariables.

During these treatment delays,many subjects or their familieshave made efforts to obtain helpand treatment, often with limitedsuccess (Lincoln and McGorry1995). In a study examining thepathways to care in first-episodepsychosis, Lincoln interviewed 62individuals and their families tomap the pathways and gain in-sight into the nature and ex-perience of delayed treatment. Thestudy (Lincoln and McGorry, inpress) used qualitative and quan-

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Table 1. Duration of pretreatment phases In pre-EarlyPsychosis Prevention and Intervention Centre sample(n = 200)

DSM-III-R diagnosis

Total samplenMeanSDMedian

Schizophrenia onlynMeanSDMedian

Schizophreniform onlynMeanSDMedian

Nonschizophrenia/schizophreniformnMeanSDMedian

Note.—DSM-lll-R - Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised.(American Psychiatric Association 1987). SD «• standard deviation.

Duration ofprodrome

(days)

130455.7818.8172.5

52779.2

1089.9390.5

27139.3273.0

32.0

51293.3538.1137.0

Duration ofuntreatedpsychosis

(days)

200193.7615.6

25.0

61508.9

1035.0122.0

4828.133.310.5

9169.7

160.114.0

titative methods to examine threeseparate aspects of the process ofdelay: help-seeking, recognition,and referral. The mean number ofcontacts was 4.5, with a range of1 to 17. Nearly one-third (29%)had one to three contacts, 55 per-cent had four to six contacts, and16 percent had more than sixhelp-seeking contacts. These figuresare comparable, though a littlelower, than those reported in theNorthwick Park Study (Johnstoneet al. 1986). General practitioners(GPs) appear to have a significantpotential role in recognition, al-

though this is not currently real-ized in practice. Thirty-five percentof initial help-seeking contactswere with a GP, although somepeople avoided their own GP. Asmany as 50 percent had contacteda GP at some point before initialeffective treatment, yet this figurecontrasts with the fact that only 5percent of referrals for specialistpsychiatric care came from GPs.Fifty percent of subjects were al-ready psychotic by the time theyfirst sought help. Early in thehelp-seeking process, subjects fre-quently sought help themselves

(40% at first contact); later on, ittended to be relatives and otherswho would seek help on their be-half. The pathways were highlyvariable and experienced in dif-ferent ways by each person andhis or her family.

The Impact of Delay. In a fash-ion similar to that of Loebel et al.(1992), we examined the relation-ship between the duration of un-treated psychosis in particular anda series of outcome measures inthe sample of 200 cases describedabove. Because of the skewed na-ture of the data. Spearman correla-tion coefficients were computed.The duration of untreated psy-chosis was moderately correlatedwith the duration of psychoticsymptoms during the first hospital-ization (r - 0.33, p < 0.001) andwith scores on the Brief PsychiatricRating Scale (BPRS; Overall andGorham 1962) (r - 0.26, p - 0.002)and on the Scale for the Assess-ment of Negative Symptoms(SANS; Andreasen 1982) (r - 0.26,p - 0.002) at 12-month followup.Moreover, the Global Assessmentof Functioning score (GAF; Ameri-can Psychiatric Association 1987)(r - -0.31, p < 0.001) and theQuality of life Scale score (QLS;Heinrichs et al. 1984) (r - -0.38,p < 0.001) at 12 months werenegatively correlated with the du-ration of untreated psychosis.When we divided the sample intothose with a duration of untreatedpsychosis of more than 28 days(approximately half) and thosewith a duration of less than 28days, we found that there weresignificant differences in durationof psychotic symptoms in the hos-pital (until remission or stabiliza-tion at reduced and stable levels)and in levels of BPRS, SANS,

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GAF, and QLS scores extendingacross the first year of followup,commencing during the initial re-covery phase and tending tostrengthen by the end of the firstyear (table 2). Much better levelsand rates of recovery were seenwith the shorter duration of un-treated psychosis.

Clearly, other variables, such asdiagnosis, could be correlated withduration of untreated psychosisand could be seen as "explaining"the associations described. It couldbe that more severe illnesses withpoorer outcomes might be charac-terized by features such as per-secutory ideation or social with-drawal that might lead to delayedpresentation, and we did find suchsymptomatic correlations in thedata. To the extent this was true,the attractive notion that therecould be an independent and po-tentially reversible contribution tooutcome of delayed treatmentwould be illusory. While this canbe clarified properly only by anintervention study, it seems logicalthat delay itself can be viewed asa dynamic and dependent variablewith a number of contributing fac-tors, and the course and outcomeof disorder is also a complex andvariable process. Multivariate anal-yses of the above data suggestthat, depending on the order inwhich other variables—such as di-agnosis (schizophrenia/schizo-phreniform; bipolar/depression;mixed), gender, and age at onset—are entered in a multiple regres-sion (excluding four cases of delu-sional disorder) with the 12-monthoutcome variable QLS score as thedependent variable, the duration ofuntreated psychosis can explainapproximately 15 percent of thevariance. When added to durationof prodrome, it can explain ap-

Table 2. Relationship of duration of untreated psychosiswith outcome over the Initial 12-month followup phasepostrecovery (pre-Early Psychosis Prevention and InterventionCentre sample, n = 200)

Duration of untreated psychosis

< 28 Days > 28 Days

Duration of psychotic symptomsbefore remission orstabilization1

BPRSEntryRecovery2

3 mos12 mos3

SANSEntryRecovery4

3 mos12 mos2

QLS3 mos2

12 mos3

GAFEntry3 mos12 mos3

30.7 days (29.1) 48.3 days (38.5)

25.8 (10.4)9.5 (6.2)9.8 (6.4)8.0 (6.7)

25.8 (21.0)11.9 (14.1)26.0 (20.9)19.1 (18.8)

68.8 (24.7)82.4 (26.3)

25.3 (9.4)55.9 (16.0)64.2 (14.4)

24.8 (8.2)11.6 (6.2)11.8 (6.9)11.6 (8.3)

30.7 (20.8)22.7 (18.8)29.8 (20.3)28.6 (21.7)

59.8 (22.5)64.8 (26.7)

25.5 (17.0)51.5 (6.2)54.2 (14.1)

Note.—Values are mean (± standard deviation). BPRS = Brief Psychiatric Rating Scale(Overall and Qorham 1962) (18 items); SANS = Scale (or the Assessment of NegativeSymptoms (Andreasen 1982); QLS » Quality of Life Scale (Helnrichs et al. 1984); QAF *Global Assessment of Functioning (American Psychiatric Association 1987).

1p < 0.0001.2 p < 0.05.3 p < 0.01.*p < 0.001.

proximately 24 percent. If diag-nosis (using all major DSM-III-Rcategories of psychotic disorder) isentered before these variables, it ac-counts for a maximum of 8 per-cent of outcome variance; if after-ward, only 1 percent. The meanQLS scores at 12 months for themajor diagnostic groupings wereas follows: schizophrenia /schizo-phreniform (n - 78) 67.9 (SD 26.1);psychotic mood disorder (n = 29)

88.5 (SD 25.7); and other (n - 26)73.2 (SD 27.4). Bonferroni post hocanalyses revealed significant dif-ferences between the schizo-phrenia /schizophreniform and psy-chotic mood disorder groups.Surprisingly, in this age range, theage at onset and gender explainedvery little of the outcome variance(< 1%). These findings are consis-tent with those of Loebel et al.(1992) and support a prima facie

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case that duration could be a rela-tively independent and importantinfluence on short-term outcome.

Initial Evaluation of theEPPIC Program

One of the explicit aims of EPPICwas to evaluate the effectivenessof the program and thus deter-mine whether early interventiondoes in fact improve the outcomeof young people experiencingtheir first episode of psychosis.While the program was not judgedto have reached optimum"evaluability" by early 1993, wenonetheless felt that an initialevaluation would be appropriate.

Evaluation of outcome in mentalhealth care is a notoriously diffi-cult and complex task. Ruggeriand Tansella (1995) distinguish be-tween efficacy (the potential of atreatment under experimental or"controlled" conditions) and effec-tiveness (the result obtained in"real world" clinical practice).They pointed out that efficacystudies are extremely difficult inclinical psychiatry because of theunavoidable intrusion of "realworld" factors. These factors in-clude the difficulty in describing,measuring, and maintaining thecontent and quality of multimodalinterventions and in distinguishingbetween specific and nonspecificand effective and ineffective treat-ment elements. Naturalistic effec-tiveness studies ideally are com-prehensive and measure effective-ness along several dimensions, in-cluding psychopathology, socialfunctioning, and quality of life.The present study is a naturalisticlongitudinal study with multidi-mensional outcome measures, aim-ing to evaluate the effectiveness of

the EPPIC program on 12-monthoutcome in first-episode psychosis,in contrast to the previous modelof care—which, it should be re-membered, also differed to a sig-nificant extent from "standardcare." Future reports will comple-ment this study with data on con-sumer satisfaction and caretakerburden, as well as cost-effective-ness (Moscarelli et al. 1991).

Method.Subjects. Subjects were com-

pared on a range of variables toevaluate the short-term effective-ness of the EPPIC program. Thefirst or experimental sample (n -51) was drawn from patients pre-senting to EPPIC with a firstepisode of psychosis during theperiod March-October 1993. Thespecific inclusion criteria for EPPIC(see above) had to be strictlymet—namely, age at onset for firstpsychotic episode between 16 and30 and currently psychotic, as evi-denced by delusions, hallucina-tions, marked formal thought dis-order, or grossly disorganized,bizarre, or inappropriate behavior.Exclusion criteria for the evalua-tion sample (but not the service it-self) included organic mental dis-order, mental retardation, epilepsy,and inadequate command ofEnglish. These subjects consentedto detailed initial assessment dur-ing the first episode and to fol-lowup on two occasions duringthe 12-month period following ini-tial recovery, at 6 months and 12months.

The 51 patients who agreed toparticipate in the evaluation studywere not significantly differentfrom nonparticipants on the fol-lowing variables: age, sex, maritalstatus, duration of inpatient care,ethnicity, and educational level.

Sample characteristics are reportedin table 3. The control sample wasdrawn from the sample of 200cases described above who weretreated and followed up (in thiscase at 3 months and 12 months)during the pre-EPPIC period 1989-92, within the first-generationmodel of care outlined earlier.Fifty-one control cases were se-lected through a precise matchingprocedure involving the followingvariables: age, sex, diagnosis, mari-tal status, and premorbid function-ing as measured by the PAS.These variables were' selected be-cause of their expected relationshipwith the key outcome variables ofinterest. The same variables wereexamined for the subsamples ofeach cohort reassessed at the 12-month followup (EPPIC n - 37;pre-EPPIC n = 34). This assess-ment indicated that the followupsamples were representative of theinitial cohorts of subjects, since nosignificant drift occurred on thesekey clinical and demographic vari-ables. These data and othercharacteristics of the EPPIC andpre-EPPIC samples are reported intable 3.

Interventions. The two cohortsexperienced significantly differentmodels of intervention, and thepre-EPPIC sample constituted ahistorical control group. The lattergot high-quality inpatient care dur-ing the initial psychotic episodeand often during any early read-mission. However, this was time-limited and short term, with poorcontinuity of care and follow-through. No proactive efforts weremade at early detection or case-finding. The EPPIC sample re-ceived the above inpatient ex-perience where this was indicated(eight cases were never admitted),but in addition they were treated

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Table 3. Sample characteristics of matched Early PsychosisPrevention and Intervention Centre (EPPIC) and pre-EPPICgroups at baseline and 12-month followup

EPPIC Pre-EPPICEPPIC Pre-EPPIC 12/12 12/12

baseline baseline completers completersn = 51 n = 51 n = 37 n = 34

Age (yrs), mean(SD)

Age at onset (yrs),mean (SD)

Gender, M/FDiagnosis, %

SzSfSaDelBipDepPsyNOS

Marital status, %Never marriedSeparatedMarried

PAS index, mean(SD)

22.0 (3.7)

21.5 (3.7)33/18

45.111.89.82.0

13.711.85.9

88.22.09.8

11.8 (8.1)

22.4 (3.9)

21.7 (4.2)33/18

45.111.89.82.0

13.711.85.9

84.32.0

13.7

11.9 (7.5)

22.0 (3.6)

21.4 (3.5)21/15

41.716.713.92.8

11.111.12.8

86.12.8

11.1

11.8 (8.6)

22.1 (3.6)

21.1 (3.9)21/13

50.014.711.80

11.811.80

85.3

14.7

12.5 (8.2)

Note.—SD = standard deviation; M = male; F = female; Bip = bipolar disorder Del =delusional disorder; Dep = depression; PsyNOS = psychotic disorder not otherwise specified;Sa = schizoaffectlve disorder; Sf = schlzopnreniform disorder Sz ° schizophrenia. PAS indexIs a subset of Hems from the Premorbid Adjustment Scale (Cannon-Spoor et al. 1982)general subscale. Some Items that were potentially confounded with onset of disorder or notapplicable to the full age range of the sample were removed.

with relatively better continuity ofcare and offered a broader rangeof services over the full period offollowup as described above.

Assessment protocols. A rangeof assessments were completed onall study participants at four dif-ferent time points: at entry to theprograms, at recovery or stabiliza-tion of psychotic symptoms, at 3months postrecovery (pre-EPPIC)or 6 months postrecovery (EPPIC),and at 12 months postrecovery.

Although there were some dif-ferences between the two studiesin the measures used, largely dueto the advent of the COPE evalua-tion project (Jackson et al. 1995), acommon core of instruments wasused in both samples. All subjectswere assessed during the initialepisode using the Royal Park Mul-tidiagnostic Instrument for Psy-chosis, a comprehensive diagnosticinstrument involving structured in-terviews completed with patients

and informants (McGorry et al.1990b, 1990c) and, wherever possi-ble, the PAS.

The BPRS and the SANS werecompleted at all assessment timepoints. At the 3- or 6-month and12-month followup points only, theQLS was completed. The QLS is a21-item semistructured interviewdesigned to assess deficit syn-drome symptoms in schizophrenia;in fact, it represents an excellentbroad spectrum measure of multi-ple outcome domains in this popu-lation. A treatment questionnairewas also completed at these fol-lowups. This is a structured inter-view developed by the researchersto assess the type and quantity offollowup care being received, aswell as any relapses or hospitaliza-tions the subject may have had inthe time between interviews. Medi-cation dosage, compliance, and anyalternative treatment or therapiesthe patient may be engaged inwere also assessed.

Interrater reliability was estab-lished for all the above measures(e.g., McGorry et al. 1988, 1990c)and monitored throughout thestudy. There was some change ininterviewers during the period inquestion, but extensive trainingand calibration of ratings mini-mized the impact, and two raterswere involved in collecting thedata in both pre-EPPIC and EPPICsamples. Mean kappas for baselineand followup ratings were almostexclusively greater than 0.7; for ex-ample, the kappa value for the di-agnosis of schizophrenia was 0.92.

Results. The outcomes of thetwo samples were compared on arange of variables. These variablesmay be grouped from proximal todistal as process or interveningvariables, symptomatic outcomevariables, and functional outcome

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variables. The results are reportedin tables 4 and 5. Finally, somebroader outcomes covered by morequalitative research carried outduring the same period are re-ported in a general way.

Process variables. The durationof untreated psychosis in the twomatched samples is reported intable 4. Since this variable is corre-lated with others that have beenconstrained by matching, and be-cause we are also examining it asa dependent variable throughwhich to evaluate the effectivenessof the early detection efforts of theEPAT team, we have also includedthe data on duration from themost complete pre-EPPIC (n -200) and EPPIC (n = 145) samplesavailable. For the latter unmatchedsamples, the duration parametershave also been presented sepa-rately for the schizophrenia andnonschizophrenia diagnostic sub-groups. This was not feasible forthe matched samples because ofthe relatively small sample size.Data for the period 1986-89 weresimilar to those for the 1989-92period.

The results reveal an apparenttrend for the duration of untreatedpsychosis to be reduced in theEPPIC sample, a trend that isstronger in the schizophrenia sub-group. This appears to amount toa reduction of approximately 1month on average in the totalsample and 5 months in the schiz-ophrenia subgroup. In reality, thenumerical change is accounted forby a reduction in the variability ofthe sample, which took placethrough a major reduction in thenumber of outliers with extremelylong durations of untreated psy-chosis. It appears that the EPATteam's efforts may have led to theearlier identification and entry into

Table 4. Duration of untreated psychosis (DUP) in pre-EarlyPsychosis Prevention and Intervention Centre (EPPIC) andEPPIC samples, days

DUP

All diagnosesMeanSDMedian

Schizophrenia, n = 55MeanSDMedian

Nonschizophrenia,n = 90MeanSDMedian

Evaluation

EPPICn = 51

191.4483.6

52.0

———

———

samples

pre-EPPICn = 51

236.6702.7

30.0

———

———

Unmatched

EPPICn = 145

158.9346.5

42.0

348.8504.3184.0

42.963.916.0

samples

pre-EPPICn = 200

193.7615.6

25.0

508.91035.0

122.0

55.3132.2

14.0

Note.—SD = standard deviation.

treatment of many more of thissubsample of cases. Although thisseems to be a clinically importantdevelopment, support is not forth-coming from tests of statistical sig-nificance. To use these tests, thedata, which are highly skewed,were log transformed, minimizingthe influence of outliers. Non-parametric methods were used asan alternative approach (Mann-Whitney U test). The result was asignificantly longer duration in theEPPIC sample, which is counterin-tuitive given the original raw data.Removal of the "outliers" influ-ence, the possible existence of afloor effect, and difficulty in inter-preting the overlap of the onsetand delay phases with the sam-pling periods all may be contribut-ing to the confusing effect.

Table 5 includes the frequencyof admissions and number of bed-

days used in the two samples ofpatients over the first 12 monthsafter program entry. The EPPICsample experienced significantlyfewer admissions (p < 0.01),mainly by avoiding the initial in-patient stay in eight cases. Also,twice as many pre-EPPIC patientsrequired more than three admis-sions. The eight EPPIC cases whoavoided admission probably wouldhave been admitted in the pre-EPPIC period. Further, with closermonitoring of outpatients throughthe outpatient case managementsystem, more relapses may havebeen detected, enhancing thetreated prevalence of acuteepisodes. The effect on readmis-sion rates is difficult to determine,however, since early detection ofrelapse may have averted readmis-sion in an unknown number ofcases.

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Table 5. Process, symptomatic, and functional outcome variables during first 12 months oftreatment

Variable

Frequency of admission01-2> 3

Inpatient bed daysTotalExcluding first admission

Neuroleptic dosage in chlorpromazineequivalentsMaximum initial dosageCases on neuroleptics only

On dischargeAt 3/6 monthsAt 12 months

All casesOn dischargeAt 3/6 monthsAt 12 months

BPRSEntryRecovery3/6 months12 months

SANSEntryRecovery3/6 months12 months

QLSEntryRecovery3/6 months12 months

Pre-EPPIC

0 (0.0%)42 (82.4%)9 (17.6%)

79.5 (61.6)25.4 (45.1)

776.9 (640.7)

398.9 (266.8)346.4 (266.9)388.7 (295.6)

350.3 (282.4)247.4 (274.8)306.3 (307.1)

25.5 (7.5)9.8 (6.1)

11.2 (6.9)11.4 (9.0)

29.7 (19.2)15.3 (15.7)27.1 (17.9)27.8 (21.6)

——

66.0 (21.9)68.8 (27.3)

EPPIC

8 (15.7%)39 (76.5%)4 (7.8%)

42.0 (31.3)9.6 (20.3)

354.0 (217.6)

267.2 (179.0)235.0 (133.6)215.7 (143.3)

253.5 (184.2)117.5 (151.2)122.4 (152.1)

27.5 (8.1)11.5 (5.6)8.1 (6.0)

10.7 (6.4)

34.5 (24.5)26.5 (20.6)17.7 (18.5)18.8 (18.1)

——

82.7 (24.2)84.7 (22.6)

P

< 0.01

< 0.0010.026

< 0.001

0.0160.0580.012

0.0720.0100.003

NSNS

0.031NS

NS0.0030.024

NS

< 0.0010.009

Note.—EPPIC - Early Psychosis Prevention and Intervention Centre. Values are mean (standard deviation). BPRS - Brief Psychiatric RatingScale (Overall and Qorham 1962); SANS = Scale tor the Assessment ot Negative Symptoms (Andreasen 1982); QLS = Quality of Life Scale(Heinrtehs et al. 1984). NS - not significant.

As a precursor to a more formaleconomic evaluation of the model,we also report the actual numberof bed-days in the two samplesfor the 12-month period after entry

ing the initial admission. Highlysignificant differences were found.In a similar vein, the duration ofthe initial admission was signifi-cantly shorter in the EPPIC (« -

days) compared with the pre-EPPIC (n - 51) sample (mean 54.1,SD - 37.1 days) for those casesadmitted during the initial episode(p - 0.021). Reductions of this

to treatment, including and exdud- 41) sample (mean 395, SD - 21.8 magnitude represent significant po-

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tential cost savings, provided theoutpatient costs of the EPPIC pro-gram do not turn out to be sub-stantially greater than standardoutpatient care. Further reductionsin the length of stay have sinceoccurred.

Adherence to treatment was as-sessed through the treatment ques-tionnaire and was rated using anumber of information sources,namely the subject, the case recordor case manager, and (where indi-cated) a relative or informant. Ad-herence was very good, and nosignificant differences were foundwhen the 3-month (pre-EPPIC) and6-month (EPPIC) followup sampleswere compared. At 12 months,there was again a surprisinglygood level of adherence overall inboth samples.

Data on neuroleptic dosage(table 5) show a substantial reduc-tion in both acute and postacutelevels of neuroleptic dosage. Thedata are presented both for the to-tal sample (including thoseneuroleptic-free at followup) andseparately for those actually receiv-ing neuroleptic medication.

These data reveal significantlylower levels of neuroleptic intakeoverall, explained partly by fewercases being prescribed neurolepticsthroughout the full 12 months offollowup (only half the samplewas still receiving neuroleptics at 6months) and partly by a low-doseprescribing policy, which has beenreduced further since this samplewas treated, influenced by thestudy of McEvoy and colleagues(1991). These data should be con-sidered in relation to levels ofsymptomatic outcome. The lowerpercentage of patients on continu-ing medication, particularly neuro-leptics, is a consequence of a num-ber of factors. First, less than half

the sample initially met criteria forschizophrenia, and more rapid andcomplete resolution is relativelymore likely in this group. Second,in a cohort of young people withno prior exposure to mental healthservices, relatively good or com-plete recovery, and significant lev-els of (partially adaptive) denial, aflight into health is common.Many of these young people aredetermined to cease medication,yet they are often willing to re-main in some degree of clinicalcontact. Our preference is gener-ally to go along with this (unlessthere are contraindications) ratherthan to attempt to enforce ad-herence (McGorry 1995a), althoughthis is often necessary in the initialacute phase. This is in keepingwith the preventive, developmen-tal, and consumer-oriented ap-proach outlined above. Further-more, we still are poor atpredicting the subgroup that willnever relapse, yet we believe it isimportant to give them an oppor-tunity to be identified relativelyearly. We nevertheless aim for atleast 6 to 12 months of neuroleptictherapy in patients meeting criteriafor schizophrenia or schizophreni-form disorder and are most reluc-tant to agree to cessation of medi-cation if positive symptoms persist,even at attenuated levels. This isbased on the admittedly limitedliterature in this area and ourclinical experience to date. A rangeof factors influence the targetedrange of duration of therapy. Italso seems wise to continue treat-ment for a period after remissionto allow for consolidation. In moretypically affective psychoses, asimilar duration of therapy isaimed for, though perhaps the 6-to 9-month timeframe is morecommon.

Symptomatic outcome variables.These data (table 5) show that lev-els of severe psychopathology, asreflected in the total BPRS score,are comparable during the first 12months in the two samples. Levelsof negative symptoms, however,follow a different pattern, withsignificantly higher levels in theEPPIC sample at the initial stabil-ization or recovery point but sig-nificantly lower levels during sub-sequent followup. The tablereports the mean total score (in-cluding global scores); however,similar results were obtained usingglobal scores alone. Beck Depres-sion Inventory (BDI; Beck et al.1961) scores were also measured;they were low and not signifi-cantly different in the two samplesat all four measurement points.These data are interesting sincethey illustrate that good remissionand low subsequent levels of posi-tive symptoms are possible withlower doses of neuroleptics (cf.Baldessarini et al. 1995). The latterstrategy, combined with intensivepsychosocial management, is alsoassociated with sustained lowerlevels of negative symptoms dur-ing the followup period. We re-main uncertain whether this re-duction involves "primary" or"secondary" negative symptoms,although the existence of very sim-ilar and low levels of depressionin each sample suggests that thereduction in negative symptoms isnot due to less depression or de-moralization per se. The reduceddoses and duration of neuroleptictherapy could, however, be a fac-tor. This issue is the focus ofongoing research.

Finally, the symptomatology as-sociated with post-traumatic stressdisorder (PTSD) was measuredusing the Structured Interview for

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PTSD Pavidson et al. 1989) in theEPPIC sample and contrasted withlevels found in the pre-EPPICsample. These data will be re-ported in more detail elsewhere,but dimensionally1 at least, signifi-cantly lower levels of these symp-toms were reported, even thoughlevels were relatively low in bothsamples. The data were as followsat the 3- or 6-month point: EPPICsample, mean 6.7 (SD = 5.3); pre-EPPIC sample, mean 10.6 (SD =7.7, p - 0.029). However, the find-ing was less clear-cut beyond thematched samples, with few dif-ferences found. Use of this meas-ure in our other research samplesresulted in means of 24.4 (SD =14.6) in a refugee trauma group (n- 69) and 32.1 (SD = 13.5) in agroup of torture survivors (n = 56)(Thompson, personal communica-tion, 1995).

Functional outcome variables. TheQLS scores during the 3- or6-month followup phase and at 12months for the two samples reflecta significant and clinically impor-tant advantage for the EPPIC sam-ples, amounting to a 23 to 25 per-cent functional improvement (table5). The QLS was originally devisedto measure aspects of deficit syn-drome in schizophrenia. One ofthe subscales, "intrapsychicfoundations"—which includesitems such as sense of purpose,motivation, curiosity, anhedonia,and emotional interaction—particularly aims to tap into what

'The global level of PTSD symp-toms rather than categorical presenceor absence of caseness due to fulfill-ment of the DSM criteria; the latter isoften quixotically determined by aparticular combination of lack offeatures.

McGlashan (personal communica-tion, 1995) has called "deficit proc-esses." We found highly significantdifferences between the two sam-ples on this subscale at the 3- or6-month followup (p - 0.005) andthe 12-month followup (p - 0.003).Apart from role functioning, thedifferences on the other subscalesof the QLS were less dramatic,suggesting that there may havebeen a direct effect on primarynegative symptoms and "deficitprocesses." This is a crucial focusfor further research.

Mixed-effects regression models(sometimes also referred to as ran-dom regression models) were fit-ted to the BPRS, SANS, and QLSdata over the different time peri-ods. This analysis confirmed thefindings reported in table 5 anddemonstrated significant differencesbetween the samples on these out-come variables at the various fol-lowup points. Further details areavailable on request.

Other outcome variables. Duringthe study period (1993-94), a con-sumer satisfaction survey was car-ried out to sample opinions amongconsumers and caretakers fromboth pre-EPPIC and EPPIC sam-ples (Lincoln 1994). The results in-dicated some improvements in sat-isfaction among consumers andcaretakers, especially in relation tofamily support; however, a numberof areas for potential further im-provements were highlighted, nota-bly the perceived and actual safetyof female inpatients in a unitwhere males predominate, theneed for better continuity of care,and levels of boredom and frustra-tion among involuntary inpatients.

Suicide rates among recent-onsetpatients are disturbingly high(Meltzer and Okayli, 1995) and yetare difficult to measure, even in

carefully defined samples. To date,over three calendar years, weknow of seven definite suicidesamong our patients, two unex-plained deaths (no evidence of sui-cide at post mortem), and one vio-lent death (shot by police). Foursuicide attempts narrowly failed.This pattern has occurred in thecontext of an inception rate of 250per annum, provision of followupcare for up to 2 years, and astanding active caseload of approx-imately 300. In the pre-EPPIC era(1989-92), to the best of ourknowledge, at least six cases fromthe pre-EPPIC 12-month followupsample (n = 140) had committedsuicide within 2 years of entry totreatment. This seems to indicate asubstantial reduction in early sui-cides, although rates are difficultto specify accurately. We are cur-rently attempting to quantify thiscritical variable more accurately,since in Australia as elsewhere,there is great concern at the dra-matic increase in the general sui-cide rate among males ages 15-24over the past 15 years (Common-wealth Department of HumanServices and Health 1995). Clearly,there may be a toxic interaction ofrisk factors here and it will be im-portant to monitor mortality care-fully from this and other sources.

Discussion—A Stitch InTime ...?

This article describes the concep-tual framework underpinning acomprehensive and relatively large-scale "real world" clinical servicethat is attempting to deliver sec-ondary prevention of psychoticdisorders in young people. TheEPPIC program has evolved from

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the first-generation model, whichprovided inpatient service only, toa comprehensive multicomponentprogram with skilled case manage-ment at its core. The model is in-formed by the recognition that theonset of psychotic illness is a po-tentially catastrophic event in ayoung person's life, with wide-reaching effects on the family, thepeer network, and educational andvocational attainment (Kessler etal. 1995). This event or processpresents a significant opportunityfor preventive work to minimizeits negative impact, as well as ameasure of reversible secondarydisability, maximizing recovery. Itis hoped that by attending to thespecific needs of this population, amore appropriate and effectiveservice has been developed thatwill continue to evolve and ul-timately lead to better short- andlong-term symptomatic and func-tional outcomes for these youngpeople. The twin strategies in-volved can be summarized asearly case detection and intensivebiopsychosocial treatment for asustained period early in thecourse of disorder. The aim is toreduce the level of both primaryand secondary morbidity associatedwith these potentially devastatingillnesses, the effects of which aremagnified through the timing oftheir peak age at onset during anexquisitely sensitive developmentalphase. What can we concludefrom the data presented?

First, the methodology of theevaluation study is by no meansperfect, and it represents a prelim-inary naturalistic or "real world"study of effectiveness rather thanof efficacy (Ruggeri and Tansella1995). On the other hand, thestudy evaluates the work of abusy frontline clinical service,

rather than a "boutique" style ofresearch intervention. Hence, itmay have more widespread ap-plicability. However, the controlgroup was not a concurrent ran-domly allocated sample but a his-torical control group, with allthe potential pitfalls associatedwith this method. On the otherhand, the controls were carefullymatched on key variables relatedto outcome, and the results clearlyfavored the experimental or EPPICsample, even though the historicalcontrols clearly were exposed to aclinical model that was superiorto even concurrent standard ap-proaches to the care of first-epi-sode psychosis patients in main-stream psychiatric services. Thisfactor probably leads to an under-estimation of the degree of advan-tage of the EPPIC model over careof first-episode cases in standardservices, as does the timing of thestudy so early in the developmentof the program. One criticism ofthe use of historical controls isthat generic and often unmeasuredchanges in the wider service cancovertly lead to differences in out-come between controls and experi-mental subjects. Significant changeswere beginning to occur in thegeneral psychiatric service systemin Victoria during the period 1989-93. But when we accessed thestandard information system(PRISM) to monitor changes inmean duration of inpatient stay inacute units—a potentially sensitiveindicator of the local changes thatinvolved an increasing shift tocommunity care of acute epi-sodes—this variable was found tobe highly stable throughout theperiod under consideration. Wehad considered, for example,whether the reduction in inpatientbed-days from the control (pre-

EPPIC) sample to the experimental(EPPIC) sample might have beenpart of a more general phenome-non; however, there was no evi-dence that such was the case. Sim-ilarly, we could find no evidencefor a generalized reduction in neu-roleptic dosage beyond the EPPICprogram—a stability that has beenreported elsewhere (Baldessarini etal. 1995). The finding that func-tional outcomes are better with re-duced neurolepuc dosages (andduration of treatment)—withoutany increase in positive symp-tomatology during followup or useof inpatient resources and with areduced level of negativesymptoms—should be of greatpractical importance.

Second, our conclusions must re-main cautious at this stage, sincethe followup period is short. Wehave no firm data yet on the out-comes for these cases at 2 yearsor beyond, although this followupis in progress. Nevertheless, thesignificant reduction in negativesymptoms and in the symptomswithin the QLS linked to deficitprocesses are especially encourag-ing. At least some of this reduc-tion may be due to lower levels ofsecondary negative symptomslinked to lower levels of neurolep-tic intake; however, it is also pos-sible that a more fundamental psy-chobiological change has occurred.If so, it may reflect the plasticityin relation to these deficit proc-esses noted by McGlashan (per-sonal communication, 1995). Thisquestion is now the subject ofmore detailed inquiry.

Third, although there has beensome impact on reducing the du-ration of untreated psychosis, theresults are not easy to interpret,and there is room for improve-ment. In addition, our approach to

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secondary prevention has been ofthe "omnibus" variety, in whichwe have targeted delay and deliv-ered more comprehensive andmultimodal early treatment at thesame time. It is therefore difficultto separate and apportion the rela-tive improvements in outcome todifferent aspects of the model ofintervention. This is likely to bemore feasible by using some ofthe designs conceived and articula-ted by McGlashan and Johan-nessen (19%, this issue), and itwill be practical in the near futurein our service setting, as well asin Norway. At mis stage, however,we believe that the improvedshort-term outcomes we have dem-onstrated derive largely from morephase-specific and intensive treat-ment than from earlier provisionof treatment, since the latter doesnot seem to have occurred to awidespread extent apart from asubsample of "outliers." We re-gard the decade-long gestationperiod during which we were ableto develop substantial clinical ex-perience with this phase of illnessas critical. Rather than merely ap-plying standard "accepted" treat-ment at an earlier phase of disor-der, we have actually modifiedtreatments for use at this phaseand developed some new clinicalexpertise in both a process andcontent sense, moving toward abest-practice model. This is a con-tention we are formally testing ina series of studies in progress, dis-mantling and evaluating the sepa-rate components of the interven-tion package. We expect thatglobal outcomes will improve fur-ther, since the program is func-tioning in a more integrated andsophisticated manner than whendie evaluation sample reportedhere was treated.

Future directions include thebetter definition of optimal psycho-pharmacological strategies and se-quences in the first episode; theearly identification of treatment-resistance and the development ofan integrated psychopharmacologi-cal and psychosocial response tothis key phenomenon; and thepushing back of the frontiers ofearly psychosis into the prepsy-chotic phase (McGorry et al. 1995),as described more fully elsewhere(Yung et al. 1996, this issue). Weare also conducting an evaluationstudy with concurrent controls anda formal cost-effectiveness study ofthe model. Finally, if the EPPICmodel is shown to be clearly cost-effective in a sustained way, thenthe question of whether and howit can be replicated must be ad-dressed more systematically.

The early intervention paradigmdeveloped within EPPIC may alsohave much wider application forother potentially serious mental ill-nesses that emerge during adoles-cence and early adult life. Theseinclude mood disorders, eating dis-orders, the more severe personalitydisorders, and some disabling anx-iety disorders such as obsessive-compulsive disorder. The modelwould require modification forsome of these disorders where theprevalence differs substantiallyfrom psychosis; however, theadage "a stitch in time savesnine" may be equally applicable.The interpretation of proverbs wasonce a time-honored assessmenttool in schizophrenia. Perhaps thisparticular saying and its simple,but elusive, underlying message—reinforced with increasing amountsof encouraging data—can help usto transform attitudes to treatmentand reorient our efforts in the careof the seriously mentally ill.

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Acknowledgments

The authors would like to ac-knowledge the contribution of Pro-fessor Bruce Singh, who initiatedthe establishment of the originalclinical research structure, theAubrey Lewis Unit, and who hassince given generous and skillfulsupport at key developmentalpoints. We also acknowledge themajor role played by AssociateProfessor Jayashri Kulkami in thegrowth of the clinical model overa number of years. ProfessorsDavid Copolov and Helen Herr-man also made an invaluable con-tribution, particularly from aresearch standpoint. A large num-

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ber of highly committed and cre-ative clinicians and researchershave also contributed to develop-ing and improving the programand continue to do so. We alsoacknowledge the strong support ofHealth and Community Servicesfor the clinical service. The re-search funding for the programprovided by the Victorian HealthPromotion Foundation through aresearch program grant "Preven-tive Strategies in Early Psychosis,"which has established the EarlyPsychosis Research Centre, and ad-ditional support from the Aus-tralian National Health and

Medical Research Council Schizo-phrenia Research Unit and theUnited States-based Stanley Foun-dation have also been an indispen-sable catalyst to the developmentof the Early Psychosis Preventionand Intervention Centre. Wewould also like to thank PaulDudgeon (M5c.) for his expert sta-tistical advice and Theresa Chengfor her invaluable assistance inpreparing the manuscript.

The Authors

Patrick D. McGorry, Ph.D.,F.R.A.N.Z.C.P., is Director, Early

Psychosis Prevention and Interven-tion Centre (EPPIC) and AssociateProfessor, Department of Psychia-try, University of Melbourne, Park-vule, Victoria, Australia. JaneEdwards, M.A., MAPS, is AssistantDirector (Clinical); CathrineMihalopoulos, B.B.S., is Researchand Evaluation Officer; and SusanM. Harrigan, Grad. Dip. Appl. Sci.,is Statistician, Department of Psy-chiatry, University of Melbourne,Parkville, Victoria, Australia. HenryJ. Jackson, Ph.D., FAPS, is Associ-ate Professor, Department of Psy-chology, University of Melbourne,Parkville, Victoria, Australia.

Recent Books Gaebel, W., and Awad, A.G. Pre-diction of Neuroleptic TreatmentOutcome in Schizophrenia: Conceptsand Methods. New York, NY:Springer-Verlag, 1994. 216 pp.

Howe, G. Working With Schizo-phrenia: A Needs Based Approach.New York, NY: Taylor & Francis,1995. 195 pp.

Moscarelli, M.; Rupp, A.; andSartorius, N. Handbook of MentalHealth Economics and Health Pol-icies: Schizophrenia. Vol. 1. West

Sussex, United Kingdom: JohnWiley & Sons, 1996. 546 pp.

Pearson, V. Mental Health Care InChina: State Policies, ProfessionalServices, and Family Responsibilities.London, England: Gaskell, 1995.218 pp.

Torrey, E.G. Surviving Schizophre-nia: A Manual for Families, Con-sumers, and Providers. New York,NY: Harper-Perennial, 1995.409 pp.

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Documents

An Evolving System of Early Detection and Optimal Management