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 Recently, interest in expanding the study of outcome in schizophrenia and related psychotic disorders has increased from a focus on purely clinical measures to other equally important dimensions of psychosocial functioning, such as employment, community adjustment, and QoL (1–6). Outcome in these latter dimensions remains relatively poor for most patients (7), despite improved pharmacologic treatment (8) and strong empirical support for the efficacy of several psychosocial interventions (9,10). Variations in outcome are likely to be influenced both by relatively stable and nonmalleable factors such as age of onset (11,12), sex (13,14), structural brain abnormalities (15), and premorbid adjustment (16–19), and by factors that are more likely to be susceptible to the inluence of the environment and deliberate interventions, such as quality of treatment, specificity of treatment, and timely access to treatment. As part of the efforts to improve outcome through influencing malleable predictors, we have recently seen a great deal of interest in treatment of early phases of the illness. This interest in early intervention has led to significant controversy and debate. In this review, we examine conceptual issues related to early intervention, together with relevant evidence. While we confined our review to studies reported between 1995 and 2005, we included earlier studies if they contained information that was novel and (or) relevant. This report does not include a formal metaanalysis of data reported in various studies. What Is Early Intervention?There is some inconsistency and conceptual confusion in the use of the terms early intervention, early psychosis, and FEP. Etymologically, early intervention suggests simply an earlier timing of intervention; however, early intervention refers not just to earlier timing of treatment but also to providing treatment specifically for needs associated with this phase of illness (20). In the following sections, we explore both these components of early intervention. To deal with the confusion that exists with terms such as early-phase psychosis, we distinguish between studies of patients who meet DSM-IV criteria for a psychotic disorder and studies that deal with patients who have been defined as meeting criteria for prodromal phase or UHR mental states. This distinction is important owing to differences in the evidence for efficacy and in the relevance of ethical issues related to treatment. Finally, because a diagnosis of schizophrenia during a first episode is likely to restrict the samples largely to patients with poor outcome (21), we have included studies of patients with a first onset of a psychotic disorder within the larger schizophrenia spectrum (that is, schizophrenia; schizophreniform, schizoaffective, and delusional disorders; and psychosis not otherwise specified) (17,18). While we present information on outcome generated from studies involving patients with FEP, some of these studies were conducted in programs that would be considered early intervention services, whereas others were conducted in routine care. Wherever possible we have made these distinctions. In general, early intervention services comprise a set of interventions enriched for the specific purpose of addressing issues relevant to this phase of the illness; care delivery is flexible and mostly uses a case management program. Most of these services also try to promote early treatment, although interventions to specifically reduce treatment delays are not incorporated in all. We have therefore separated studies that specifically evaluated the effect of reducing delay from those that only incorporated nonspecific efforts for early treatment as part of the overall service. Rationale for a Phase-Specific Early Intervention Approach to Treating FEPThere is evidence that trajectories of long-term outcome in schizophrenia may be identified and determined within the first 5 years of the illness (22,23). If so, a relatively narrow window exists for interventions to influence longer-term outcome. The concept of an initial critical period (24) is supported by data from prospective longitudinal studies of FEP (25). The relation between early course and long-term outcome is not necessarily causal and may or may not be modifiable. If it is possible to change the trajectory of illness by intervening earlier, then it is probably also important to address the particular circumstances of patients during those first few years. Patients with FEP, mostly adolescents or young adults, have needs that are likely to be different from the needs of previously treated patients with more established outcome trajectories (26,27). For example, FEP patients are likely to be naive, not only to the effects of antipsychotic medication but also to the vagaries of the mental health system. Patients’ initial experience with medication, especially with side effects, strongly predicts their future adherence to treatment (28). Given the importance of treatment adherence for future prognosis, a specialized approach to initiating antipsychotic medication may be desirable to ensure future engagement in treatment. Unfortunately, most FEP patients are reluctant to accept treatment readily and are often admitted to hospital involuntarily (29,30). Studies of pathways to care for FEP patients reveal the complexities of the mental health system, which is difficult for patients and families to negotiate (31,32). Only a small proportion of patients seek treatment specifically for psychotic symptoms (32). Further, most patients present with diagnostic uncertainties (33–35) and multiple problems, such as suicidal (29,36,37) and aggressive (29) behaviour, as well as legal difficulties (29) that can result in further delays if they are diverted to other systems such as the criminal justice system. Difficulties in engaging and retaining young treatment naive patients are also likely to be major sources of failure in our approach to patients with FEP. The psychosocial circumstances of young patients with FEP present additional challenges, which include negotiating developmental trajectories disrupted by the onset of the illness, issues related to personal identity, relationships outside the family, and educational and occupational goals. Patients with FEP are often still living with and dependent on family, who are likely to provide a most valuable resource for treatment and whose involvement may be even more critical and accessible at this stage than during later stages. Phase-specific treatment must therefore incorporate principles of treatment shown to be effective in schizophrenia and related disorders and must modify them to meet the specific needs of this patient population. Several model early intervention programs have been developed in the last decade (see 38 for details). Common elements of these programs include some variation of assertive case management, almost exclusive use of low dosages of novel antipsychotic drugs, close monitoring of symptoms and functioning, family intervention, and individual and group psychotherapeutic and cognitive-behavioural intervention (38). Treatment is usually sustained for a period varying from 18 months to 2 years or longer (38,39). Although the enthusiasm in regard to the potential benefits of a specialized early intervention service has resulted in significant shifs in policy and resource allocation in some jurisdictions (England and Wales, for example), it has also created a continung debate about the rationale and feasibility of these new shifts in service development (40–42). Are Specialized Early Intervention Programs Effective?We report separately on evidence regarding the effectiveness of specialized early intervention services for clinical, functional, and QoL outcomes, and we review available data regarding predictors of outcome for each dimension. Clinical Outcome Clinical outcome is usually reported according to measures of remission and (or) relapse (that is, rate of and time to), proportion of patients improved, and level of residual positive and negative symptoms following a set period of treatment. We report separately results of studies based on samples of subjects with FEP evaluated at entry and follow-up without a comparative treatment control group (uncontrolled studies) and studies that either used a quasi-experimental design (historical controlled studies) or an experimental design (randomized controlled studies). Remission and Improvement in Psychopathology: Uncontrolled Studies. Most uncontrolled studies cover a period of 1 to 2 years. High rates of remission, ranging from 75% to 85%, have been reported in most studies conducted within the context of early intervention services and using mostly novel antipsychotics (17,43–47). Similar rates of remission were reported in earlier studies conducted in routine care with typical antipsychotic medications (48,49) and without any special measures for service delivery or interventions specific for FEP; however, these studies reported on hospitalized subjects with FEP and (or) subjects recruited for research purposes and using a standardized medication protocol (48,49). Early intervention services have generally reported on more representative samples within defined catchment areas and have included patients who were not hospitalized or who suffered from comorbid substance abuse. The definitions of remission have considerable similarities and are usually based on symptom ratings. Most studies have reported significant improvement in positive, negative, depressive, and anxiety symptoms, although the magnitude of change in negative symptoms has been generally more limited than that reported for positive symptoms (17,43). Most studies, including those conducted within the context of routine care (49,50), have examined predictors of remission and (or) residual symptoms at the end of 1 year of treatment or longer. Predictors of higher levels of positive symptoms at 1 year include longer DUP (17,43,44,49), poor premorbid adjustment (17,18,50), longer prodromal symptoms (51), and the level of dysrhythmia seen on routine EEG (52,53). Predictors of higher levels of negative symptoms after at least 1 year of treatment include poor premorbid adjustment (17,18), longer DUP (43), and EEG reports of dysrhythmia (52,53). Given the potential importance of DUP as a malleable predictor of outcome, it is important to note that not all studies have reported longer DUP to be related negatively to symptomatic outcome (54, see 55 for details). Remission and Improvement in Psychopathology: Quasi-Experimental and Randomized Controlled Studies. A phase-specific approach to treatment in Australia has been reported to show superior outcome in regard to positive and negative symptoms, relative to historical comparison data (43). More recently, 2 RCTs have reported on the efficacy of a specialized intervention in FEP. Reporting on results of an RCT of a specialized service, compared with standard care, in 144 FEP patients, Craig and others failed to find differences in recovery rates over a period of 18 months (56). However, their definition of recovery is not synonymous with the term remission as used in other studies and is based on information derived from case notes. A comparison of the 2 groups failed to reveal a significant difference in estimated treatment effects on insight or on level of positive or depressive symptoms. It showed a marginal effect on negative symptoms (P = 0.05) and a significant effect on adherence to medication (P = 0.03) (57). After adjustment for ethnicity, sex, and previous episode, the difference in medication adherence remained marginally significant (P = 0.05), whereas the effect on negative symptoms did not. In a more recent RCT of specialized early intervention service (the OPUS study, 58–60), first-episode schizophrenia spectrum psychosis patients (n = 547) were randomized to a specialized service or standard care. Results at 1 year revealed an estimated mean difference between groups of –0.31 (95%CI, –0.55 to –0.07; P = 0.02) on psychotic symptoms and –0.36 (95%CI, –0.54 to –0.17; P = 0.001) on negative symptoms in favour of specialized treatment. Corresponding differences at 2 years were –0.32 (95%CI,–0.58 to –0.06; P = 0.02) and –0.45 (95%CI, –0.67 to –0.22; P = 0.001). At 1 year, patients in the specialized treatment also had significantly less comorbid substance abuse (16% vs 22%, OR 0.5, P = 0.03), lower rates of treatment discontinuation (8% vs 22%, OR 0.3, P = 0.001), and more satisfaction with treatment (estimated mean difference 1.88; 95%CI, 0.73 to 3.02; and estimated mean difference 3.09; 95%CI, 2.10 to 4.04; P = 0.001, at 1 and 2 years, respectively). Relapse. Rates of relapse following treatment of a first episode of schizophrenia spectrum psychosis in routine care range from 30% in the first year to 80% within the first 5 years (22,61). Short-term (within 15 months) relapse rates for a largely adolescent sample of patients with FEP treated in a specialized early intervention service were reported to be relatively low, ranging from 16% (meeting both symptom-based and clinical criteria) to 26% (based on symptom ratings) and 29% (based on clinical criteria) (44). Low relapse rates (17% and 29% at 1 and 2 years, respectively) have also been reported from another specialized early intervention service in a sample of patients with FEP (n =107) (47). This study covered a wider age range (16 to 50 years) and used a definition of relapse based on symptom ratings and a weekly log of clinical status. Three RCTs have reported on relapse or hospital readmission rates. The first RCT (62) compared family intervention added to standard care with standard care alone in a Chinese sample of 78 male patients with first-episode schizophrenia. The results showed hospital readmission rates of 14% and 50%, respectively (relative risk 0.28; 95%CI, 0.13 to 0.62; P = 0.002). The standard care, however, involved minimal treatment and is not comparable to standard care reported generally. Given the limited range of interventions provided, this study cannot be considered as an evaluation of a specialized early intervention service. A recent RCT (56) of a specialized treatment service reported a 30% full or partial relapse, compared with 48% in standard care, over an 18-month period (OR 0.46; 95%CI, 0.21 to 0.97; P = 0.04) (56). Readmission rates were 33% and 51%, respectively (OR 0.48; 95%CI, 0.24 to 0.97; P = 0.04). Except for the total number of readmissions to hospital, these differences were nonsignificant after adjusting for baseline differences for sex, previous psychotic episodes, and ethnicity. In addition, patients in the specialized treatment group were more often in regular contact with their respective clinical teams (86%, compared with 68%; OR for lost to care 0.35; 95%CI, 0.15 to 0.81). While these results provide some support for the superior efficacy of specialized early intervention treatment services for FEP, the effect sizes may have been limited by the relatively small number of patients involved. Assessment of relapse may also have been compromised by reliance on hospital records data only. A more recent RCT (58–60) did not report on relapse rates specifically but provided data on the proportion of patients not admitted to hospital and the number of days spent in hospital during the follow-up period. The results favour the specialized treatment on both measures at 1 year. The proportions of patients not admitted to hospital during the first year were 41% and 29%, respectively, for specialized and standard care (OR 1.79; 95%CI, 1.09 to 2.94; P = 0.02). The mean number of days spent in hospital were 62.2 and 78.9, respectively (OR –16.8; 95%CI, –33.5 to –0.05; P < 0.05). At 2 years’ follow-up, however, there were no significant differences on these measures. Outcome for Community and Social Functioning and QoL Although syndromal recovery has been reported for most patients with an FEP, fewer patients make a functional recovery (23). It has been observed that, while residual symptoms have some influence on community functioning as a measure of outcome (63,64), other important factors (for example, cognitive functions) may influence aspects of functional recovery such as employment (65) and social functioning (64). A large overlap exists between definitions of functional outcome and QoL outcome; however, for this review, we have separated studies that examine outcome in regard to employment and social and community functioning from studies that examine issues related specifically to QoL, such as life satisfaction and well-being. Vocational Functioning. The evidence from uncontrolled studies suggests a wide variation in the proportion of patients who fulfill role functions (that is, who are employed, in educational programs, or in full-time housework and child care) and are financially independent. Short-term (that is, 1-year) studies have reported rates of “adequate role functioning” ranging from 51% in routine care in an Indian sample of first-episode schizophrenia patients (66) to 59.9% in a Canadian sample of patients with schizophrenia spectrum psychoses receiving early intervention services (67). Two-year rates vary from 32% (68) to 40% (69) for first-episode schizophrenia patients. While the former study (68) used a specialized approach, it is unclear whether the latter study (69) referred to routine care. Longer-term studies conducted only within the context of routine care suggest lower rates of vocational adjustment, ranging from 25% at 5 years (15) to 8% at 10 years (70). Rates of financial dependence on state or other sources have been reported to range from 64% (69) to 53% (68). Results from an RCT comparing specialized and standard care also failed to show any significant differences in vocational outcome between the 2 treatment conditions (57). There is a great deal of variation in the measures used (for example, the proportion of individuals employed and the number of hours worked weekly; see 71) and in whether comparative data at the point of entry to the program are provided. An examination of predictors of vocational adjustment following treatment of FEP has produced various significant associations with poor outcome, including poor premorbid adjustment (67), negative symptoms at initial assessment (69), concurrent psychotic and negative symptoms (67), and poor global cognitive functions and lack of cerebral asymmetry (15). With one exception (66), none of the studies found delay in treatment to be related to vocational outcome. It must be emphasized that no studies have reported the incorporation of any specific interventions to improve vocational outcome in FEP in either routine or specialized early intervention treatment programs (see 71 for a more detailed review). Social Relations and Community Functioning. Outcomes for other aspects of functioning, such as ability to live independently and maintain social relations, have also been recently reported in patients treated for FEP, mostly in the context of examining the relation of social outcome to other aspects of the illness or to patient characteristics (15,37,64,69). Improved outcomes in social and familial relationships (64,66) and in dimensions of community functioning have been reported at the end of 1 year’s treatment of FEP in a specialized service in Canada (64), as well as in a routine treatment program in India (66). In a sample of young FEP patients, a delay in receiving psychosocial treatment has been associated with more time spent in hospital during follow-up but not with social outcome (72). Harrigan and others (73) reported that, in addition to other variables such as female sex and good premorbid adjustment, greater improvement in functional outcome was related to an early intervention treatment model. None of these studies had a comparison group, and change was reported within the sample from point of entry to treatment to the time of follow-up. An RCT of specialized care, compared with standard care, recently reported a significant effect of treatment on GAF scores (P = 0.01) and on differences in the proportion of patients with social relationships at 18 months (55% vs 25%, P = 0.001), but it reported no differences in independent housing (57). Results of studies examining predictors of social and community functioning suggest that negative symptoms (64,69), premorbid adjustment (35,64), medication adherence (37,64), residual symptoms (64), and cognitive functions—especially, working memory (64)—each independently influence aspects of social and community functioning. Follow-up studies of FEP with onset of psychosis in childhood and adolescence have reported even worse functional outcome, as indicated by social disability and deviation from expected norms on educational and occupational outcome (74) and by GAF scores, scores on the Strauss–Carpenter Scale, and data on independence in living arrangements and finances (75). These latter 2 studies involved samples not exposed to any specialized early intervention treatment approaches. Quality of Life. Interest in health-related QoL has been stimulated by higher expectations related to the introduction of newer antipsychotic medications (76–78) and by the increased power of patients and their families to voice their expectations regarding mental health services. Both subjective and objective measures of QoL have been regarded as valuable methods of assessment (3,4,79–83). Few studies have been conducted in FEP to specifically examine the differential effects of treatment, although several studies mostly comparing before and after treatment for 1 to 2 years have reported changes in QoL following treatment of FEP. Significant improvement in QoL measured on the Quality of Life Scale (3) has been reported after 1 year of treatment in a large sample of subjects with FEP (n = 200) receiving a specialized service (43). QoL at 1 year was negatively related to DUP, independent of effects of age of onset, sex, and diagnosis (43). Similar improvements have been reported from a smaller Canadian sample (n = 41) of FEP patients treated in a specialized service (84), both on an overall index of self-assessment according to the Wisconsin QoL Scale (85) and on individual dimensions such as psychological well-being and satisfaction with life. In another, larger Canadian sample, Addington and others (67) reported improvement of QoL in subjects, following 1 year of treatment in a specialized service, compared with an age- and sex-matched control sample. The improved QoL in this study was related to remission status, level of negative symptoms, and premorbid adjustment. An RCT of specialized care, compared with standard care, reported significant estimated treatment effects on satisfaction with services (2.98; 95%CI, 0.62 to 5.33; P = 0.01) and QoL (–7.08; 95%CI, –12.47 to Summary Evidence from at least one controlled study and most uncontrolled studies suggests that, compared with routine care, a specialized early intervention approach to treatment of FEP results in modestly superior benefits for a wide range of patients, through high rates of remission, better control of symptoms, and greater adherence and retention in treatment, as well as benefits related to some aspects of functional outcome, satisfaction, and QoL, defined broadly. There is little evidence that early intervention has any differential benefits for vocational outcome, although none of the early intervention services have used specific interventions for improving vocational outcomes. The benefits, such as low relapse rates, have so far been demonstrated only in the short term (1 to 2 years) while patients are receiving relatively intensive treatment. The obvious question is whether the benefits of specialized intervention can be sustained over a longer time without continuing intensive intervention. A 5-year follow-up of young FEP patients treated in an early intervention service for 15 months and then transferred to routine care in the community showed a rather poor outcome with high rates of relapse and disability (44). Further studies are required to determine what level of care needs to be provided after the initial intensive and specialized intervention to sustain benefits of a specialized service. Delay in Treating FEP and the Potential for Early InterventionDelay in treating psychosis, expressed usually as DUP, is the time between the onset of psychotic symptoms (syndromal threshold) and the onset of adequate antipsychotic treatment, defined as continuous antipsychotic medication for 1 month or until remission of psychotic symptoms occurs, whichever comes first (17,86). The rationale for reducing delay in treatment of psychotic disorders is based on 1) the postulate that longer experience of psychosis may have toxic effects that interfere with recovery (87,88) and aspects of social functioning (82,89), 2) the frequently reported relation between DUP and several outcome indicators (43,55,90,91), and 3) recognition of the fact that untreated psychosis in itself represents significant unnecessary suffering for patients and their families. While the relation between naturally occurring differences in DUP and outcome has been replicated in several studies, results are not entirely consistent (50,54,55,92), and there continue to be ambiguities associated with interpreting correlational evidence only (55). Most early intervention services incorporate some efforts to promote early treatment, but only a few have examined the impact of systematic interventions on DUP. Reducing DUP: Interventions to Promote Early Case Identification If the treatment delay is causally related to clinical (17,18, 43,49) and (or) social (55,82) outcomes, reducing DUP should lead to improved outcome according to clinical and social measures. A more fundamental question, therefore, is “Can DUP be reduced through an intervention, and if so, does such reduction in DUP lead to improved outcome beyond what can be achieved through specialized treatment?” If these objectives can be met, such knowledge would be transferable to appropriate health care settings, with positive implications for mental health policy and service delivery to this most vulnerable population. Effectively reducing treatment delay requires an understanding of the nature and source of this delay and finding effective interventions to reduce it (32,93). Pathways to care traversed by patients with FEP are likely to vary, depending on the organization of health care services and access to primary or specialist care. For example, patients with FEP tend to follow somewhat similar pathways in Australia and Canada, where access to specialized health care is usually controlled through primary care (32); this differs from systems where patients have direct access to specialists (for example, in France; 31) or where access to public mental health care for first-time help seekers is limited (for example, in the US). A recent Canadian study showed that at least one-half of the delay in treatment occured after patients first contacted health services (usually primary care or emergency services) following onset of active symptoms of psychosis and that, at some point in their pathway to care, most FEP patients were assessed either in a hospital emergency department (68%), by a family physician (55%), or by a psychiatrist (44%) (32). On average, patients with FEP made 2.5 visits to health services prior to receiving treatment, and, while most made their first contact with some aspect of primary health care (38.5% and 34.3% with family physicians and emergency services, respectively), few were admitted to psychiatric treatment after their first presentation. A recent report from France also revealed that most patients (88%) had multiple help-seeking contacts prior to treatment of FEP, that 70% of these failed contacts were with a health care professional, and that 70% have had this contact with a family physician or a psychiatrist (31). Others have noted that pathways to psychiatric treatment through primary care providers can be particularly slow (94); it has been suggested that primary care can be a key factor in reducing DUP and in facilitating access to sustained treatment (95). There are as yet no reports evaluating interventions to reduce DUP directed specifically at primary care. With regard to the ethical implications of randomizing patients to early or delayed treatment to test the impact of an intervention to reduce DUP (90), it is more feasible to use a quasi-experimental design. Thus far, no study has reported any data concerning change in clinical and social outcome as a result of reduced DUP. A brief review of the studies that have examined the impact of interventions to reduce delay follows. Historical Control Studies The EPPIC Study. The EPPIC, located in Melbourne, Australia, incorporated strategies to encourage referrals from family physicians and other community sources at an early stage of the illness and provided a specialized, phase-specific treatment approach (43). The researchers compared 51 patients who had been treated for their first episode of psychosis in the new EPPIC program with a matched historical control group of 51 patients treated in a routine manner. While significant improvement in treatment outcome was reported for patients treated in the EPPIC program, there was only a suggestive (that is, not statistically significant) reduction in DUP as a result of introducing the EPPIC program. In fact, after its introduction, several patients referred for treatment proved to have had an extremely long DUP. This suggests that patients previously untreated for long periods may enter treatment as a result of such early intervention strategies. TIPS Project. This Scandinavian study, carried out in the Rogaland (Norway) health sector (population 260 000) compared 2 groups with a first episode of schizophrenia spectrum disorders assessed and treated in 1993–1994 or 1997–1998 (96,97). The former (historical control) sample was recruited through routine methods primarily involving inpatient hospital admissions. During 1997–1998, an early detection system was implemented, consisting of special detection teams, extensive educational campaigns about psychosis in the general community, and targeted information campaigns directed at primary sources of referral. The results showed that, compared with the historical control group, the early detection sample were younger, had a DUP that was shorter by 21.5 weeks, and showed better premorbid functioning, lower level of positive, negative and general symptoms, and higher level of substance abuse. The difference in DUP was statistically significant only for women. There are several problems associated with interpreting these data as evidence that early detection programs based on community education resulted in reduced DUP. These include the long gap between the historical control sample and the intervention sample and differences in access to types of treatment (inpatient only, compared with more comprehensive in and outpatient treatment). Access to treatment (rather than community education) may have had the most important effect on patients’ willingness to enter treatment. Prevention and Early Intervention Program for Psychosis Project. This project, intended to reduce DUP and located in London, Ontario, was carried out in 2 phases. In the first phase, as part of initiating a new specialized service, it introduced several systemic changes. These included a referral system that was open to any source, prompt assessment within 72 hours, and flexibility in the location of the initial assessment. An evaluation of these systemic changes showed a substantial but statistically nonsignificant reduction in DUP over a 3-year period (98). In the second phase, a community focused early case identification program was carried out over 2 years (January 2000 to February 2002). The program used multiple media sources and consisted of a community-wide education campaign regarding early psychosis and the benefits of early treatment. The primary outcome measures assessed were DUP and patient characteristics. Patients in Phase II presented with statistically greater severity of psychotic and disorganization symptoms, compared with those in Phase I. Contrary to expectation, DUP remained unchanged following the intervention (median DUPs for Phases I and II were 21.9 weeks and 24.3 weeks, respectively; mean DUPs were 74.1 and 96.6 weeks, respectively; Mann–Whitney Z = 0.20, ns) (99). Parallel Control Studies The TIPS project also compared one sector (population 370 000) that received an ED program with another sector (population 295 000) where no ED program was added (100). The results reported recently indicate that DUP was significantly shorter in the ED sector (median 5 weeks, range 0 to 1196 weeks) compared with the non-ED sector (median 16 weeks, range 0 to 966 weeks) (for the combined sample, the median was 10 weeks and the mean was 49.1 weeks). The ED-sector patients had a lower level of symptoms at the time of entry to the program (101). This is the only study to have reported a reduction in DUP as a consequence of a community-based intervention. However, an examination of the impact of reduced DUP on clinical or other aspects of outcome has so far failed to reveal any beneficial impact (101). Summary Efforts to reduce DUP have produced mixed results. Possible explanations for the apparent inconsistency between findings from different studies include composition of the population served in terms of such variables as ethnicity, immigration, and the level of services available; variations in pathways to care; the extent to which primary health care sources of referral are specifically targeted; and the ability of the community intervention to reach the most relevant segments of the population. Delay in treatment is a highly complex phenomenon mediated and moderated by several other factors, such as premorbid adjustment and mode of onset, as well as by local systemic factors. Efforts to influence delay in treatment must take into consideration the many factors other than public awareness that are associated with seeking help. These include referral patterns from initial points of contact to an appropriate service and the time taken to engage patients in treatment, even after they are referred to a specialized service. Each component of delay may require a different intervention strategy. Interventions in the Prodromal PhaseAlmost invariably, FEP patients report noticeable changes in behaviour and functioning, and often clear psychiatric symptoms, prior to the onset of psychosis (102–104). This prodromal period can only be defined retrospectively. There is, however, evidence that considerable disability is often associated with this phase (104) and that the total duration of such prodromal symptoms may be more predictive of outcome than is the period of psychosis alone (51). Intervention during this phase prior to the onset of psychosis could be attractive if it prevented or delayed psychosis onset. The relatively nonspecific nature of typical prodromal symptoms for predicting psychosis has led to a shift in the focus of preventive work primarily to individuals considered to be at UHR for psychosis. Determining UHR status is based on a combination of predispositional and experiential factors, such as family history, disruption of functioning, and (or) brief or subsyndromal experiences related to psychosis (103,105). Longitudinal follow-up of UHR individuals has revealed a 1-year conversion rate of 30% to 40% (105), making it feasible to test interventions to prevent or delay conversion to psychosis. Several intervention studies have been conducted to reduce the rate of conversion from UHR to psychosis. McGorry and others reported a significantly lower 1-year rate of conversion to psychosis for UHR patients (total n = 59) randomized to treatment for 6 months with low-dose risperidone and a modified version of cognitive therapy, compared with patients with no antipsychotic medication and routine supportive care (RR 0.27; 95%CI, 0.08 to 0.89) (106). Results of this pioneering study suggested a ratio of 3.9 (95%CI, 2 to 20) for number needed to treat. The effect of intervention was no longer seen at 12 months (RR 0.54; 95%CI, 0.23 to 1.30), and no longer term follow-up data are yet available. It is also difficult to separate the effect of the cognitive intervention from that of antipsychotic medication, because the experimental condition combined the 2 treatments. A second study has involved a double-blind, randomized allocation of UHR patients to olanzepine or placebo (107,108). Preliminary results suggest a lower rate of conversion to psychosis for the olanzapine group. A more recent study has tested the efficacy of CBT provided for 6 months in a randomized controlled design, compared with monitoring alone, with a total follow-up of 1 year (109). Reported results suggest that CBT resulted in a significantly lower conversion to psychosis (diagnosed according to DSM-IV criteria) and lower use of antipsychotic medications. In another open study of intervention in the prodromal phase, 62 adolescents were separated into 3 groups according to the profile of their symptoms. The rate of conversion to psychosis was related to the severity of the initial presentation and adherence to medication, suggesting that intervening while symptoms are not too severe may reduce conversion rates (110). These findings are difficult to interpret, because patients were prescribed medication according to their needs as assessed by their clinicians without any randomization to alternate treatments. Summary While some evidence is indeed emerging in favour of the ability of medical and (or) psychological interventions to prevent conversion to psychosis in individuals considered to be at UHR for a psychotic disorder, several methodological, conceptual, and ethical issues need to be resolved in future studies before such interventions are included in routine practice. For example, it remains to be seen 1) whether these interventions prevent incidence cases of psychosis or arrest progression to a more severe state of psychosis with already established, albeit milder, illness; 2) whether preventive interventions are effective in all potential cases or only in those that would have had a good prognosis; 3) whether harm done by treatment is significantly less than benefit obtained and whether such a level of harm is acceptable to patients; and 4) whether all options of treatment have been tested in this phase of illness. It is beyond the scope of this paper to provide a detailed review of the conceptual, methodological, and ethical complexities associated with intervention during the prepsychotic phase. ConclusionShort-term outcome in first-episode psychosis may be improved with enrichment of treatment through a specialized service comprising a phase-specific early intervention approach to treatment together with some strategies to make treatment available early. Interventions during the putative prodromal phase will require further investigation, owing to greater ethical concerns and limited evidence to support such interventions. A recent Cochrane review of early intervention studies in psychosis arrived at similar conclusions about treatment during the prodromal phase, but this review was somewhat less enthusiastic about the impact of specialized treatment on clinical and social outcomes in FEP (111). The discrepancy in the conclusions may be partly related to the addition of the OPUS study results (58–60) in this review and to generally more restrictive criteria for including outcome studies in the Cochrane review. 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