Yuta Saito1, Hitoshi Sakurai2, John M Kane3, Nina R Schooler4, Takefumi Suzuki5, Masaru Mimura6, Hiroyuki Uchida7. 1. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Neuropsychiatry, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan. 2. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, New York, USA; Department of Psychiatry and Molecular Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y, USA; Center of Psychiatric Neuroscience, The Feinstein Institute for Medical Research, New York, USA. 4. Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, New York, USA; Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, New York, USA. 5. Department of Neuropsychiatry and Clinical Ethics, University of Yamanashi, Yamanashi, Japan. 6. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. 7. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: hiroyuki_uchida@keio.jp.
Abstract
INTRODUCTION: Little attention has been paid to the contribution of individual residual symptom to predict relapse in patients with schizophrenia receiving oral or long-acting injectable (LAI) antipsychotics. METHOD: We used the data from the Preventing Relapse on Oral Antipsychotics Compared to Injectables - Evaluating Efficacy (PROACTIVE) study, in which 305 outpatients with schizophrenia were randomly allocated to either biweekly LAI-risperidone (LAI-R) or daily oral second-generation antipsychotics (SGA) and assessed for up to 30 months. Baseline individual symptoms that could predict subsequent relapse were identified, using a Cox proportional hazards model. Moreover, among those who relapsed during the study (n = 73), individual symptoms were compared between baseline and biweekly ratings 8 to 2 weeks before relapse, using the linear mixed model. RESULTS: A greater score in grandiosity at baseline was significantly associated with subsequent relapse (adjusted HR = 1.24, p = 0.006). When the two treatment groups were separately analyzed, more severe grandiosity (adjusted HR = 1.43, p = 0.003) and less severe hallucinatory behavior (adjusted HR = 0.70, p = 0.013) at baseline were significantly associated with relapse in the oral SGA group, but none was identified in the LAI-R group. Emotional withdrawal was significantly worse 8 and 2 weeks before relapse compared to the baseline (p = 0.032 and p = 0.043, respectively). DISCUSSION: More severe grandiosity and less hallucination may have led to more frequent relapses in patients with schizophrenia receiving oralantipsychotics, which was not a case in those receiving LAI-R. The exploratory analysis indicates an increase in emotional withdrawal before relapse may be a useful marker for earlier interventions to possibly avert relapse.
RCT Entities:
INTRODUCTION: Little attention has been paid to the contribution of individual residual symptom to predict relapse in patients with schizophrenia receiving oral or long-acting injectable (LAI) antipsychotics. METHOD: We used the data from the Preventing Relapse on Oral Antipsychotics Compared to Injectables - Evaluating Efficacy (PROACTIVE) study, in which 305 outpatients with schizophrenia were randomly allocated to either biweekly LAI-risperidone (LAI-R) or daily oral second-generation antipsychotics (SGA) and assessed for up to 30 months. Baseline individual symptoms that could predict subsequent relapse were identified, using a Cox proportional hazards model. Moreover, among those who relapsed during the study (n = 73), individual symptoms were compared between baseline and biweekly ratings 8 to 2 weeks before relapse, using the linear mixed model. RESULTS: A greater score in grandiosity at baseline was significantly associated with subsequent relapse (adjusted HR = 1.24, p = 0.006). When the two treatment groups were separately analyzed, more severe grandiosity (adjusted HR = 1.43, p = 0.003) and less severe hallucinatory behavior (adjusted HR = 0.70, p = 0.013) at baseline were significantly associated with relapse in the oral SGA group, but none was identified in the LAI-R group. Emotional withdrawal was significantly worse 8 and 2 weeks before relapse compared to the baseline (p = 0.032 and p = 0.043, respectively). DISCUSSION: More severe grandiosity and less hallucination may have led to more frequent relapses in patients with schizophrenia receiving oral antipsychotics, which was not a case in those receiving LAI-R. The exploratory analysis indicates an increase in emotional withdrawal before relapse may be a useful marker for earlier interventions to possibly avert relapse.