Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

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Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Background Controversy remains as to whether cannabis acts as a causal risk factor for schizophrenia or other functional psychotic illnesses.

Aims To examine critically the evidence that cannabis causes psychosis using established criteria of causality.

Method We identified five studies that included a well-defined sample drawn from population-based registers or cohorts and used prospective measures of cannabis use and adult psychosis.

Results On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis.

Conclusions Cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths. Research is needed to understand the mechanisms by which cannabis causes psychosis.

/pdf/causal-association-between-cannabis-and-psychosis-1jmvzyyxn5.pdf

Causal association between cannabis and psychosis: examination of the evidence

Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features.

Objectives To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness.

Design Randomised clinical trial.

Setting Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus, Denmark.

Participants 547 patients with first episode of schizophrenia spectrum disorder.

Interventions Integrated treatment and standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre.

Main outcome measures Psychotic and negative symptoms (each scored from 0 to a maximum of 5) at one and two years' follow-up.

Results At one year's follow-up, psychotic symptoms changed favourably to a mean of 1.09 (standard deviation 1.27) with an estimated mean difference between groups of –0.31 (95% confidence interval –0.55 to –0.07, P = 0.02) in favour of integrated treatment. Negative symptoms changed favourably with an estimated difference between groups of –0.36 (–0.54 to –0.17, P < 0.001) in favour of integrated treatment. At two years' follow-up the estimated mean difference between groups in psychotic symptoms was –0.32 (–0.58 to –0.06, P = 0.02) and in negative symptoms was –0.45 (–0.67 to –0.22, P < 0.001), both in favour of integrated treatment. Patients who received integrated treatment had significantly less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment.

Conclusion Integrated treatment improved clinical outcome and adherence to treatment. The improvement in clinical outcome was consistent at one year and two year follow-ups.

https://www.bmj.com/content/bmj/331/7517/602.full.pdf

A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness

Background. The concept of duration of untreated psychosis (DUP) has recently attracted much interest because of its possible relationship to treatment outcome and implications for preventive efforts with reference to psychotic disorders, especially schizophrenia. In this paper we review critically the literature concerning the concept and its importance.Methods. Articles concerned with measuring DUP and those that have been suggested to provide indirect or direct evidence of the effect of DUP on treatment outcome are reviewed.Results. Evidence thus far suggests that DUP may be related to ease of reducing psychotic symptoms once treatment begins for first episode patients, but there is no evidence of a relationship to likelihood of relapse. There has been little investigation of the relationship of DUP to other long-term outcomes such as negative symptoms and cognitive functioning neither have the possible confounds of DUP been widely investigated or controlled.Conclusions. It is important that there should be more thorough investigations of DUP, its correlates, and the extent to which it does mediate any advantages of earlier intervention.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/2F2C3D713ACF8C5A851C8C043FBD21ED/S0033291701003488a.pdf/div-class-title-duration-of-untreated-psychosis-a-critical-examination-of-the-concept-and-its-importance-div.pdf

Duration of untreated psychosis: a critical examination of the concept and its importance.

Carbone S, Harrigan S, McGorry PD, Curry C, Elkins K. Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach.



Acta Psychiatr Scand 1999: 100: 96–104. © Munksgaard 1999.



Objective: Early intervention research is examining whether reducing the duration of untreated psychosis (DUP) leads to improved outcome from first-episode psychosis. Another key influence may be the quality of treatment after initiation of care. This study examined the effect of phase-specific treatment on 12-month outcome for different categories of DUP.



Method: A total of 250 first-episode psychosis cases were followed up 12 months after stabilization. The sample consisted of two historically sequential cohorts treated in the same region within different service models, one of which was more intensive and phase-specific. Outcome was compared according to four predefined categories of DUP.



Results: Only patients with a mid-range DUP of 1–6 months who were treated within the phase-specific model experienced significantly better outcomes than patients treated within the previous model.



Conclusion: These data suggest that there may be a limited window of opportunity in which to influence outcome. However, the complexity of this relationship is emphasized.

Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach.

Background: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis.Method: The ‘ultra’ high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrolment in the study was assessed at intake.Results: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder.Conclusion: The results of this study suggest that cannabis use may not play an ...

Cannabis use is not associated with the development of psychosis in an ?ultra? high-risk group.

BACKGROUND: The Early Psychosis Prevention and Intervention Centre (EPPIC) commenced operation in Melbourne, Australia, in 1992. It offers a model for management of first-episode psychosis, utilising principles of early detection, low-dose medication and comprehensive psychosocial interventions within the least restrictive setting. METHOD: Data were examined from the first three months of treatment for all consecutive people with first-episode psychosis (n = 231) accepted in the programme in 1995-1996. A subsample of patients (n = 120) was assessed comparing clinical ratings with variables of gender, diagnosis, hospitalisation, and medication. RESULTS: Hospitalisations were brief, and avoided for a third of the people. Low-dose antipsychotic medication was maintained in both in-patient and community settings. Those people with manic psychosis were more likely to be hospitalised. Hospitalised people received higher antipsychotic dosages, and had a greater rate of reduction in Brief Psychiatric Rating Scale psychotic subscale scores at three months follow-up. Eighty per cent of a representative subsample had responded to treatment and 63% were in remission by the end of the three months. CONCLUSION: This naturalistic study suggests that the feasibility of implementing the EPPIC model in a range of clinical settings is promising and applicable in practice.

Analysis of the initial treatment phase in first-episode psychosis.

Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia

Substantial delays in providing access to treatment in first-episode psychosis have been well documented. The present study examines the impact of strategies aimed at improving access and reducing delays. A pilot community education campaign was conducted with the aim of reducing the duration of untreated psychosis (DUP) in a geographically defined intervention sector located in the north-western region of Melbourne, Australia. Utilising a quasi-experimental design, a comparison sector with similar demographics was selected from another part of the north-western region. A mobile early detection team and the same treatment system served both sectors. While there was no significant difference between the mean DUP for intervention and comparison sectors, the distributional features of DUP between the two regions were significantly different. In the intervention sector, disproportionately more cases with very long DUP were detected. When a small number of outliers were removed, the mean and median DUP in the intervention sector was reduced. These findings highlight the complexity of treatment access and delay and suggest that efforts to reduce DUP may have two effects, not one. Firstly, a different sample of cases is treated through the detection of hidden “long DUP” cases that otherwise may have remained untreated. Secondly, the DUP for the remainder may indeed be reduced. More research with larger samples and more potent campaign strategies is clearly required. It may also be worth considering whether there is a safe and ethical way to undertake a RCT of early versus delayed antipsychotic treatment to perhaps settle the DUP debate once and for all.

Christina Curry

Papers

Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach.

Cannabis use is not associated with the development of psychosis in an ?ultra? high-risk group.

Analysis of the initial treatment phase in first-episode psychosis.

Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia

Early intervention in first-episode psychosis--the impact of a community development campaign.