Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients

Marshall, Max; Lewis, Shôn; Lockwood, Austin; Drake, Richard; Jones, Peter B.; Croudace, Tim

doi:10.1001/archpsyc.62.9.975

Cited by 1,399 publications

(1,083 citation statements)

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“…Our finding that longer DUP predicts treatment resistance is in line with evidence from a comprehensive systematic review that documented the association between longer DUP and poor outcome (Marshall et al 2005).…”

Section: Predictors Of Trosupporting

confidence: 88%

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

et al. 2017

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Background. We examined longitudinally the course and predictors of treatment resistance in a large cohort of firstepisode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.Method. The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.Results. From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.Conclusions. The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

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Section: Predictors Of Trosupporting

confidence: 88%

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

et al. 2017

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“…Thus, the prolonged treatment given would mostly have been provided in the plateau phase,48 which is when the effect of SEI teams is more questionable. Other studies have found a relation between duration of untreated psychosis and outcome,49 and one randomised controlled trial found that shortening the duration of untreated psychosis had an effect on the long term functional outcome 50…”

Section: Discussionmentioning

confidence: 99%

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Albert

Melau

Jensen

et al. 2017

BMJ

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Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual.Design Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site.Setting Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark.Participants 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203).Interventions OPUS treatment consists of three core elements—modified assertive community treatment, family involvement, and social skill training—with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment.Main outcomes Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation.Results Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference −0.10 (95% confidence interval 0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group.Conclusions This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment.Trial registration Clinicaltrial.gov NCT00914238.

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“…The first by Marshall et al reported an association at 6 and 12 months but not at baseline and 24 months (Marshall et al, 2005). The second by Perkins et al claimed that patients with shorter DUP experienced less negative symptoms at baseline and follow-up (Perkins, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…So far two meta-analyses have examined the correlation between DUP and negative symptoms (Marshall et al, 2005;Melle et al, 2008). The first by Marshall et al reported an association at 6 and 12 months but not at baseline and 24 months (Marshall et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Duration of untreated psychosis and negative symptoms — A systematic review and meta-analysis of individual patient data

Boonstra

Klaassen

Sytema

et al. 2012

Schizophrenia Research

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Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Background: Longer duration of untreated psychosis (DUP) is associated with poorer outcome in terms of positive symptoms, relapse rate, and time to remission. In contrast, the association with negative symptoms is less consistent. Aims: The study had three aims. First, to arrive at a more precise estimate of the correlation between DUP and negative symptoms than previous reviews, by substantially increasing the amount of available data. Second, to see whether the strength of this correlation attenuated over longer follow-up intervals. Third, to determine whether there is a relationship between DUP and changes in negative symptoms. Method: Relevant databases were searched for studies published between December 1992 and March 2009 that reported data on DUP and negative symptoms. We obtained individual patient data where possible and calculated summary correlations between DUP and negative symptoms for each study at baseline, short and long-term follow-up. We used multilevel regression analysis to examine whether the effect of DUP on negative symptoms was the greatest in the early stages of illness. Results: We included 28 non-overlapping studies from the 402 papers detected by the search strategy. After contacting the authors we obtained individual patient data from 16 of these studies involving 3339 participants. The mean DUP was 61.4 weeks (SD = 132.7, median DUP = 12.0). Shorter DUP was significantly associated with less severe negative symptoms at baseline and also at short (1-2 years) and longer term follow-up (5-8 years) (r = 0.117, 0.180 and 0.202 respectively, p b 0.001). The relationship between improvement in negative symptoms and DUP was found to be non-linear: people with a DUP shorter than 9 months showed substantially greater negative symptom reduction than those with a DUP of greater than 9 months. Conclusions: Shorter DUP is associated with less severe negative symptoms at short and long-term follow up, especially when the DUP is less than 9 months. Since there is no effective treatment for negative symptoms, reducing DUP to less than 9 months may be the best way to ameliorate them.

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Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients

Abstract: 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.

Cited by 1,399 publications

References 45 publications

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Duration of untreated psychosis and negative symptoms — A systematic review and meta-analysis of individual patient data

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