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A PROSPECTIVE STUDY OF THE CLINICAL OUTCOME FOLLOWING TREATMENT DISCONTINUATION AFTER 2 YEARS IN FIRST-EPISODE SCHIZOPHRENIA
Abstracts
Poster 223 A PROSPECTIVE STUDY OF THE CLINICAL OUTCOME FOLLOWING TREATMENT DISCONTINUATION AFTER 2 YEARS IN FIRST-EPISODE SCHIZOPHRENIA Lupe Martinez2, Robin Emsley1, Piet Oosthuizen1, Liezl Koen1, Dana Niehaus1 1 Stellenbosch University Cape Town, Western Cape, South Africa; 2 Janssen-Cilag Medical Affairs EMEA, Beerse, Belgium Background: An important unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a first psychotic episode. This study assessed the clinical consequences of antipsychotic discontinuation after 2 years of uninterrupted treatment in patients treated for a first episode of schizophrenia or related illness. This is a pre-specified interim analysis after 1 year of treatment discontinuation. Methods: This study is an extension of a previously published 24month, open-label study in which 50 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated with flexible doses of risperidone long-acting injection (RLAI). At the completion of that study, patients were offered enrolment in this follow-up study evaluating the effects of treatment discontinuation. Patients opting to participate in the discontinuation trial had RLAI tapered over a period of up to 6 weeks, with follow-up while off antipsychotic therapy or until relapse, defined operationally. Following RLAI discontinuation, patients were assessed every 2 months. RLAI was immediately re-instituted when relapse was identified. This is a pre-specified interim analysis of all subjects who completed 1 year of follow-up. Relapse rates, time to relapse, and antecedents to relapse were evaluated with Positive and Negative Syndrome Scale (PANSS) and Patient-assessed Global Impression of Change (PGI-C) scores. Results: Of the 50 patients who completed the 2-year treatment study, 19 men and 14 women (mean age 27.5 ± 7.9 years and baseline PANSS score of 45.0 ± 7.4) entered the discontinuation study and were followed for 1 year or until relapse. At baseline, 28 patients (84.8%) were in remission. 26 patients (79%) relapsed within 1 year. Kaplan-Meier estimate of median time to relapse was 163 days (95% CI 96–199). 8 patients were hospitalized as a result of relapse. There were no differences between those who relapsed and those who did not in terms of baseline PANSS scores or remission status. PANSS total scores remained similar to those at baseline up until (and including) the visit prior to relapse. Discussion: Similar to previously reported studies with oral and depot antipsychotics,2,3 relapse rates were high within 1 year of treatment discontinuation in patients who had been treated with RLAI for firstepisode of schizophrenia for 2 years. First relapses occurred suddenly, without clear-cut warning signs. These findings have important clinical implications, suggesting that antipsychotic discontinuation after 2 years of treatment may not be in the best interest of the majority of patients.
397
University of Amsterdam Amsterdam, North-Holland, Netherlands; DepartmentoM f ethodologyandStatistics,SchoolforPublicHealthandPrimaryCare, MaastrichtUniversityMaastricht,Limburg, Netherlands;4DepartmentofPsychology,UniversityofNorthCarolina,ChapelHill ChapelHill,NorthCarolina,USA;5DivisionofPsychologicalMedicine,Instituteof PsychiatryLondon,GreaterLondon,UnitedKingdom 3
Background: Cognitive impairment is associated with poor functional outcome in schizophrenia, a finding which has increasingly rendered cognition a target for treatment intervention. Yet, whether different cognitive domains, i.e. neurocognition or social cognition, show differential patterns of associations with functional outcome, has not been reviewed systematically. The current meta-analytic review investigates the magnitude of the associations between 9 neurocognitive and 3 social cognitive domains and different types of functional outcome. Methods: Relevant English-language articles from 1977 to present, investigating cross-sectional associations between cognition and functional outcome in individuals with non-affective psychosis were searched in MEDLINE and PsycINFO electronic databases and reference lists from identified articles. Of 283 studies identified as potentially suitable, 52 met all criteria for inclusion into the metaanalysis. Pearson correlations between cognition and outcome, demographic data, sample sizes and potential moderator variables, such as inpatient status, illness duration, age, and gender were extracted from the included articles. Results: 48 independent meta-analyses, investigating the associations between 12 a priori identified cognitive domains and 4 domains of functional outcome, were conducted on data from 52 studies comprising more than 2692 patients with non-affective psychosis. Combination of mean effect sizes (r) across studies by means of a random effects model yielded a number of 25 significant medium strength correlations that ranged from μp = .16 to .48. Overall, social cognition was more strongly associated with community functioning than neurocognition (μp = .25 vs .38). Pairwise comparisons indicated that this finding is mostly due to stronger associations with theory of mind. Discussion: Cognitive impairment as indexed by neuropsychological test scores is consistently associated with functional outcome. Social cognition, specifically theory of mind, appears to be stronger associated with current community functioning than neurocognition. Yet, approximately 76% of variance in functional outcome is left unexplained. This finding stresses the need to quest for other explanatory factors. doi:10.1016/j.schres.2010.02.719
Poster 225 COGNITIVE DYSFUNCTION AFTER RECOVERY FROM SCHIZOPHRENIA
doi:10.1016/j.schres.2010.02.718
Poster 224 A META-ANALYTIC STUDY ON COGNITION AND FUNCTIONAL OUTCOME IN NON- AFFECTIVE PSYCHOSIS: MUCH VARIANCE LEFT UNEXPLAINED Anne-Kathrin Fett1,2, Maria de Gracia Dominguez1, Wolfgang Viechtbauer3, David Penn4, Jim van Os1,5, Lydia Krabbendam2 1 Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Maastricht, Limburg, Netherlands; 2Department of Psychology and Education, Free
Amresh Shrivastava1, Megan E. Johnston2, Nilesh Shah3, Meghana Thakar4, Larry Stitt1 1 University of Western Ontario, London, ON, Canada; 2University of Toronto, Toronto, ON, Canada; 3University of Mumbai Sion, Mumbai, India; 4South London and Maudsley NHS Trust, London, United Kingdom Background: Deterioration of cognitive functioning is now viewed as a core feature of schizophrenia. The existing research on cognitive functioning in first-episode schizophrenia suggests that cognitive deficits may be present quite early on in the illness. Less is known about what happens to cognitive abilities in the years following a diagnosis of first-episode schizophrenia, particularly after individuals have, in a
Poster 223 A PROSPECTIVE STUDY OF THE CLINICAL OUTCOME FOLLOWING TREATMENT DISCONTINUATION AFTER 2 YEARS IN FIRST-EPISODE SCHIZOPHRENIA Lupe Martinez2, Robin Emsley1, Piet Oosthuizen1, Liezl Koen1, Dana Niehaus1 1 Stellenbosch University Cape Town, Western Cape, South Africa; 2 Janssen-Cilag Medical Affairs EMEA, Beerse, Belgium Background: An important unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a first psychotic episode. This study assessed the clinical consequences of antipsychotic discontinuation after 2 years of uninterrupted treatment in patients treated for a first episode of schizophrenia or related illness. This is a pre-specified interim analysis after 1 year of treatment discontinuation. Methods: This study is an extension of a previously published 24month, open-label study in which 50 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated with flexible doses of risperidone long-acting injection (RLAI). At the completion of that study, patients were offered enrolment in this follow-up study evaluating the effects of treatment discontinuation. Patients opting to participate in the discontinuation trial had RLAI tapered over a period of up to 6 weeks, with follow-up while off antipsychotic therapy or until relapse, defined operationally. Following RLAI discontinuation, patients were assessed every 2 months. RLAI was immediately re-instituted when relapse was identified. This is a pre-specified interim analysis of all subjects who completed 1 year of follow-up. Relapse rates, time to relapse, and antecedents to relapse were evaluated with Positive and Negative Syndrome Scale (PANSS) and Patient-assessed Global Impression of Change (PGI-C) scores. Results: Of the 50 patients who completed the 2-year treatment study, 19 men and 14 women (mean age 27.5 ± 7.9 years and baseline PANSS score of 45.0 ± 7.4) entered the discontinuation study and were followed for 1 year or until relapse. At baseline, 28 patients (84.8%) were in remission. 26 patients (79%) relapsed within 1 year. Kaplan-Meier estimate of median time to relapse was 163 days (95% CI 96–199). 8 patients were hospitalized as a result of relapse. There were no differences between those who relapsed and those who did not in terms of baseline PANSS scores or remission status. PANSS total scores remained similar to those at baseline up until (and including) the visit prior to relapse. Discussion: Similar to previously reported studies with oral and depot antipsychotics,2,3 relapse rates were high within 1 year of treatment discontinuation in patients who had been treated with RLAI for firstepisode of schizophrenia for 2 years. First relapses occurred suddenly, without clear-cut warning signs. These findings have important clinical implications, suggesting that antipsychotic discontinuation after 2 years of treatment may not be in the best interest of the majority of patients.
397
University of Amsterdam Amsterdam, North-Holland, Netherlands; DepartmentoM f ethodologyandStatistics,SchoolforPublicHealthandPrimaryCare, MaastrichtUniversityMaastricht,Limburg, Netherlands;4DepartmentofPsychology,UniversityofNorthCarolina,ChapelHill ChapelHill,NorthCarolina,USA;5DivisionofPsychologicalMedicine,Instituteof PsychiatryLondon,GreaterLondon,UnitedKingdom 3
Background: Cognitive impairment is associated with poor functional outcome in schizophrenia, a finding which has increasingly rendered cognition a target for treatment intervention. Yet, whether different cognitive domains, i.e. neurocognition or social cognition, show differential patterns of associations with functional outcome, has not been reviewed systematically. The current meta-analytic review investigates the magnitude of the associations between 9 neurocognitive and 3 social cognitive domains and different types of functional outcome. Methods: Relevant English-language articles from 1977 to present, investigating cross-sectional associations between cognition and functional outcome in individuals with non-affective psychosis were searched in MEDLINE and PsycINFO electronic databases and reference lists from identified articles. Of 283 studies identified as potentially suitable, 52 met all criteria for inclusion into the metaanalysis. Pearson correlations between cognition and outcome, demographic data, sample sizes and potential moderator variables, such as inpatient status, illness duration, age, and gender were extracted from the included articles. Results: 48 independent meta-analyses, investigating the associations between 12 a priori identified cognitive domains and 4 domains of functional outcome, were conducted on data from 52 studies comprising more than 2692 patients with non-affective psychosis. Combination of mean effect sizes (r) across studies by means of a random effects model yielded a number of 25 significant medium strength correlations that ranged from μp = .16 to .48. Overall, social cognition was more strongly associated with community functioning than neurocognition (μp = .25 vs .38). Pairwise comparisons indicated that this finding is mostly due to stronger associations with theory of mind. Discussion: Cognitive impairment as indexed by neuropsychological test scores is consistently associated with functional outcome. Social cognition, specifically theory of mind, appears to be stronger associated with current community functioning than neurocognition. Yet, approximately 76% of variance in functional outcome is left unexplained. This finding stresses the need to quest for other explanatory factors. doi:10.1016/j.schres.2010.02.719
Poster 225 COGNITIVE DYSFUNCTION AFTER RECOVERY FROM SCHIZOPHRENIA
doi:10.1016/j.schres.2010.02.718
Poster 224 A META-ANALYTIC STUDY ON COGNITION AND FUNCTIONAL OUTCOME IN NON- AFFECTIVE PSYCHOSIS: MUCH VARIANCE LEFT UNEXPLAINED Anne-Kathrin Fett1,2, Maria de Gracia Dominguez1, Wolfgang Viechtbauer3, David Penn4, Jim van Os1,5, Lydia Krabbendam2 1 Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University Maastricht, Limburg, Netherlands; 2Department of Psychology and Education, Free
Amresh Shrivastava1, Megan E. Johnston2, Nilesh Shah3, Meghana Thakar4, Larry Stitt1 1 University of Western Ontario, London, ON, Canada; 2University of Toronto, Toronto, ON, Canada; 3University of Mumbai Sion, Mumbai, India; 4South London and Maudsley NHS Trust, London, United Kingdom Background: Deterioration of cognitive functioning is now viewed as a core feature of schizophrenia. The existing research on cognitive functioning in first-episode schizophrenia suggests that cognitive deficits may be present quite early on in the illness. Less is known about what happens to cognitive abilities in the years following a diagnosis of first-episode schizophrenia, particularly after individuals have, in a