@article{5569cd06fcab48348e5600102dea45c1,
title = "Association of C-reactive protein and metabolic risk with cognitive effects of lurasidone in patients with schizophrenia",
abstract = "Background: Accumulating evidence has implicated insulin resistance and inflammation in the pathophysiology of cognitive impairments associated with neuropsychiatric disorders. This post-hoc analysis based on a placebo-controlled trial investigated the effect of inflammation (indexed by CRP) and metabolic risk factors on cognitive performance in patients with schizophrenia treated with lurasidone. Methods: Acutely exacerbated patients with schizophrenia were randomized to lurasidone (80 or 160 mg/day), quetiapine XR 600 mg/day, or placebo. A wide range CRP test and a cognitive assessment using the CogState computerized battery were performed at baseline and week 6 study endpoint. Associations between log-transformed CRP, high density lipoprotein (HDL), homeostatic model assessment of insulin resistance (HOMA-IR) and treatment response were evaluated. Results: CRP combined with HDL, triglyceride-to-HDL (TG/HDL) ratio, or HOMA-IR at study baseline were significant moderators of the improvement in cognitive performance associated with lurasidone 160 mg/day (vs. placebo) treatment (p <.05). Greater placebo-corrected treatment effect size on the CogState composite score was observed for patients in the lurasidone 160 mg/day treatment group who had either low CRP and high HDL (d = 0.43), or low CRP and low HOMA-IR (d = 0.46). Interactive relationships between CRP, HDL, TG/HDL, HOMA-IR and the antipsychotic efficacy of lurasidone or quetiapine XR were not significant. There were no significant associations between antipsychotic treatment and changes in CRP level at study endpoint. Conclusions: Findings of this post-hoc analysis based on a placebo-controlled trial in patients with schizophrenia suggest that baseline CRP level combined with measures of metabolic risk significantly moderated the improvement in cognitive performance associated with lurasidone 160 mg/day (vs. placebo) treatment. Our findings underscore the importance of maintaining a low metabolic risk profile in patients with schizophrenia.",
keywords = "C-reactive protein, Cognitive performance, Metabolic risk, Schizophrenia, lurasidone",
author = "Miller, {Brian J.} and Andrei Pikalov and Siu, {Cynthia O.} and Michael Tocco and Joyce Tsai and Harvey, {Philip D.} and Newcomer, {John W.} and Antony Loebel",
note = "Funding Information: Presented in part at the American College of Neuropsychopharmacology December 3–7, 2017, Palm Springs, CA, USA; 6th Biennial Schizophrenia International Research Society Conference, April 4–8, 2018, Florence, Italy; American Psychiatric Association Annual Meeting, May 5–9, 2018, New York City, USA; American Society of Clinical Psychopharmacology Annual Meeting, May 29–June 2, 2018, Miami, Florida; and 31st European College of Neuropsychopharmacology Congress October 6–9, 2018, Barcelona, Spain. This study was sponsored by Sunovion Pharmaceuticals Inc., who was involved in the design and collection of data. All authors contributed to the analysis and interpretation of data, reviewed and gave final approval for the manuscript. Funding Information: Dr. Miller received travel expenses to present the work under consideration at the 2017 American College of Neuropsychopharmacology annual meeting. In the past 12 months, Dr. Miller received research support from the Augusta University; the Stanley Medical Research Institute; NARSAD; and the National Institute of Mental Health; and Honoraria from Psychiatric Times. Dr. Siu reports consulting fees from the Chinese University of Hong Kong, and Sunovion. In the last 3 years, Dr. Harvey has received consulting fees or travel reimbursements from Teva, Takeda Pharma, Sunovion Pharma, Sanofi Pharma, Otsuka America (Otsuka Digital Health), Minerva Pharma, Lundbeck Pharma, Jazz Pharma, Intra-Cellular Therapies, Genentech (Roche Pharma), Forum Pharma, Boehringer Ingelheim. Biogen, Allergan, Akili, and Alkermes. He receives royalties from the MATRICS Consensus Battery and the Brief Assessment of Cognition in Schizophrenia. He is the chief scientific officer of i-Function, Inc. He has research grants from the Stanley Medical Research Foundation and Takeda. In the last 3 years Dr. Newcomer has received grant support from Otsuka America Pharmaceutical Co. Ltd., the Substance Abuse and Mental Health Services Administration, and the National Institutes of Health; served as a consultant to Alkermes, Auris, Indivior, Otsuka, and Sunovion; serves on a Data Safety Monitoring Board for Amgen; and has been involved in patent litigation on behalf of Sunovion. and. Drs. Loebel, Pikalov, Tsai, and Tocco are employees of Sunovion Pharmaceuticals Inc. Funding Information: This study was sponsored by Sunovion Pharmaceuticals Inc. , who was involved in the design and collection of data. All authors contributed to the analysis and interpretation of data, reviewed and gave final approval for the manuscript. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = oct,
doi = "10.1016/j.comppsych.2020.152195",
language = "English (US)",
volume = "102",
journal = "Comprehensive Psychiatry",
issn = "0010-440X",
publisher = "W.B. Saunders Ltd",
}
