Randomized Controlled Trial of Interventions Designed to Reduce the Risk of Progression to First-Episode Psychosis in a Clinical Sample With Subthreshold Symptoms

McGorry, Patrick D.; Yung, Alison R.; Phillips, Lisa; Yuen, Hok Pan; Francey, Shona; Cosgrave, Elizabeth; Germano, Dominic; Bravin, Jenny; McDonald, Tony; Blair, Alison; Adlard, Stephen; Jackson, Henry J.

doi:10.1001/archpsyc.59.10.921

Cited by 929 publications

(723 citation statements)

References 37 publications

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“…Thus far, one randomized clinical trial (RCT) has demonstrated the superiority of low dose risperidone in combination with cognitive behavioral therapy over "needs-based intervention," with a significant difference in rates of transition to psychosis (9.7% vs. 35.7%) and reported low incidence of side effects and little stigma (McGorry et al, 2002). Another RCT, which was placebo-controlled and double-blind, had differential rates of conversion to psychosis at 1 year (placebo 34.5% vs. olanzapine 16.1%) that was not statistically significant, probably due to low power ; unfortunately, weight gain was also much higher in the olanzapine group (8.8 vs. 0.3 kg).…”

Section: Defining the At-risk Populationmentioning

confidence: 99%

Prodromal interventions for schizophrenia vulnerability: the risks of being “at risk”

Corcoran

Malaspina

Hercher

2005

Schizophrenia Research

170

167

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Given the morbidity and difficulty of treating psychotic disorders, including schizophrenia, there has been a move toward identifying and treating adolescents and young adults who appear to be clinically at risk or "prodromal" to psychosis. The field now has greater specificity in identification, with rates of 40-50% conversion to frank psychosis within 1-2 years. There is further evidence that medications and other treatments may have some efficacy for "prodromal" patients, though with variable side effects. However, controversy remains about some of the inherent risks in prodromal research, such as medication exposure and stigma among false-positives. In this paper, we add to this discussion through an analysis of ethics in prodromal research from the more established field of predictive genetic testing. Issues are raised about the effects of information on patients, families, and institutions, as well as future insurability, the limits of confidentiality (as it relies on discretion of patients and families), the autonomy of minors with psychiatric symptoms, and even the risks for the true-positive patient.

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Section: Defining the At-risk Populationmentioning

confidence: 99%

Prodromal interventions for schizophrenia vulnerability: the risks of being “at risk”

Corcoran

Malaspina

Hercher

2005

Schizophrenia Research

170

167

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“…The basis of the vulnerability to psychosis in this group is unknown and, whilst evidence shows that psychological and pharmacological interventions improve outcomes (Bechdolf et al, 2005;McGorry et al, 2002;Miller et al, 2003;Phillips et al, 2005;Ruhrmann et al, 2005;Woods et al, 2003), treating high risk subjects remains controversial since most of them are not destined to develop the disease (Broome et al, 2005b;Cornblatt et al, 2001;Haroun et al, 2006). The identification of biological measures associated with a subsequent transition to psychosis would help to target early treatment to those who require it (Bender et al, 2007;Eastvold et al, 2007;Mason et al, 2004;Pantelis et al, 2003;Simon et al, 2007;van der Stelt and Belger, 2007).…”

Section: Introductionmentioning

confidence: 99%

Abnormal P300 in people with high risk of developing psychosis

et al. 2008

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Background: Individuals with an "At Risk Mental State" (or "prodromal" symptoms) have a 20-40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable.Method: 35 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression.Results: The P300 amplitude was significantly reduced in the ARMS group [8.6 ±6.4 microvolt] compared to controls [12.7 ±5.8 microvolt] (p<0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Please find attached a fully revised manuscript titled "Abnormal P300 in people with high risk of developing psychosis". We also enclose a letter with the comments from the reviewers and our detailed answers on how we have done all the changes requested. (t-test; p=0.93). Those making a transition to psychosis were marginally more educated but this was only at trend level with a 3 year average difference in the age at which they completed their studies (t-test; p=0.07).Similarly, logistic regression analyses showed that compared to those who remained at risk, the seven cases who made a transition to psychosis had no significant differences in P300 amplitude/latency or N100 amplitude/latency (p values ranging from 0.30 to 0.63 for all four analyses). We have reported these comparisons very concisely and cautiously because referee #2 said that these analyses with only 7 individual making a transition were preliminary and power is limited. Please see results section paragraph 2. RESPONSE TO REVIEWER #2:Thank you for your suggestions, which have improved the paper. Below are your comments in blue-italics and how we have amended the manuscript accordingly in black with cross-references to the revised manuscript.This paper addresses an important and timely topic, namely, whether auditory P300 is reduced in subjects with at risk mental states and whether the P300 predicts subsequent conversion to psychosis. The study finds a significant deficit in P300 in ARMS subjects, relative to controls, replicating a previously a previously published report. The study had the potential to incrementally * 2. Response to Reviews 2 contribute to the literature by examining the utility of baseline P300 deficits as a predictor of subsequent conversion to psychosis; however, the negative finding coupled with the lack of power for this analysis (only 7 converters) make this aspect of the study inconclusive. More detailed comments are provided below:We have added a paragraph in the discussion to acknowledge the limitation of our small group of converters and how we have low statistical power to compa...

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“…6 Another controlled study examined the effects of risperidone treatment on the progression of "ultra high risk" individuals defined as those with nonspecific symptoms, impaired functioning, and a first-degree relative with psychosis; attenuated positive psychotic symptoms lasting at least a week; or brief episodes of psychotic symptoms not sustained beyond a week. 7 Significantly fewer individuals went on to develop a first-episode psychosis in the group treated with risperidone.…”

Section: Treatment Of Prodromal Symptomsmentioning

confidence: 99%

“…[3][4][5][6][7] A "prodrome" of depression, decreased concentration and attention span, lack of motivation, apathy, and social withdrawal can precede the first psychotic symptoms in schizophrenia by as much as 4 or 5 years. 2,9,10 Some patients never progress beyond this phase of the illness.…”

Section: Treatment Of Prodromal Symptomsmentioning

confidence: 99%

“…1 Now comes further evidence that this pretreatment may be possible in schizophrenia, [2][3][4][5][6][7] where it is already known that atypical antipsychotics not only get you better by treating acute symptoms, but also keep you better by preventing relapse. 2,8 Is it possible that giving these agents to high-risk individuals with prodromal symptoms could prevent or delay progression to schizophrenia?…”

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