Innovations In Clinical Neuroscience

NOV-DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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23 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE November-December 2017 • Volume 14 • Number 11–12 O R I G I N A L R E S E A R C H P Poor insight, including impairments in awareness of illness, commonly occurs in patients with schizophrenia and represents a major risk factor for poor treatment outcomes. 1–8 Reduced insight has been found to be associated with poor treatment adherence; 8–11 more severe symptoms of illness;3 and various deficits in cognition, social cognition, and functional performance. 4,6,8 Improving insight is therefore a key therapeutic goal for patients with schizophrenia. 12 Poor insight in schizophrenia has been linked to reduced awareness of the presence and significance of psychotic symptoms, 13,14 impaired self-assessment of cognitive and functional performance, 15 deficits in appraising and responding to effort-based tasks, 16 and reduced subjective quality of well-being. 5,12,17–20 A recent study suggested that the inability to make an accurate self-assessment of cognition and everyday functioning skills was the most influential predictor of real-world functioning compared to clinical symptoms, cognitive performance, or functional capacity. 15 Insight impairment can bias assessment of capability in either direction, leading to the possibility of over- or under-estimation of abilities and likely outcomes. In addition, poor insight constitutes a significant barrier to accepting and adhering to treatment. 4,6,7–10,12,21 Post-hoc analysis of data from the large-scale Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)study in schizophrenia showed that patients with marked psychotic symptoms and insight deficits (as assessed by the Positive and Negative Syndrome Scale [PANSS] item G12), yet who reported being "pleased" or "delighted" with their everyday lives, were more likely to discontinue treatment and have a poorer attitude toward treatment. 8 Although lack of insight regarding illness is considered a core feature of schizophrenia, there is a paucity of information, particularly A B S T R A C T ABSTRACT: Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition (p=0.014), functional capacity (p=0.006, UPSA-B), quality of well-being (p=0.033, QWB), and depressive symptoms (p=0.05, Montgomery–Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time. KEYWORDS: Insight, schizophrenia, cognition, functional capacity, quality of well-being, depressive symptoms, lurasidone, quetiapine XR Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR by PHILIP D. HARVEY, PhD; C YNTHIA O. SIU, PhD; and ANTONY D. LOEBEL, MD Dr. Harvey is with the University of Miami Miller School of Medicine in Miami, Florida, and the Research Service of the Bruce W. Carter VA Medical Center in Miami, Florida. Dr. Siu is with COS and Associates Ltd. in Central District, Hong Kong. Dr. Loebel is with Sunovion Pharmaceuticals Inc., in Fort Lee, New Jersey. Innov Clin Neurosci. 2017;14(11–12):23–29 FUNDING: This study was sponsored by Sunovion Pharmaceuticals Inc. The sponsor was involved in the study design and collection of data. DISCLOSURES: Dr. Harvey serves as a consultant/advisory board member for Allergan, Akili, Boehringer-Ingelheim, Lund- beck, Otsuka Digital Health, Sanofi, Sunovion, and Takeda. Dr. Siu has received funding and consulting fees from Sunovion that support research and the use of lurasidone clinical trial databases for analyses and preparation of this manuscript. She has also received funding and consulting fees from Schizophrenia Program, Centre for Addiction and Mental Health, University of Toronto, Pfizer, Hong Kong Health and Medical Research Grant, and the Chinese University of Hong Kong that support research and the use of clinical trial and genetic databases for analyses, preparation of manuscripts, and data science activities. Dr. Loebel is an employee of Sunovion Pharmaceuticals. CORRESPONDENCE: Philip D. Harvey, PhD; Email:

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