title: Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.
abstract: Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.
authors.affiliation: Medical College of Georgia, Georgia Regents University, Augusta, GA; pbuckley@gru.edu.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Buckley
authors.affiliation: Downstate Medical Center, State University of New York, Brooklyn, NY; Feinstein Institute for Medical Research, Zucker Hillside Hospital, Glen Oaks, NY;
authors.forename: Nina R
authors.initials: NR
authors.lastname: Schooler
authors.affiliation: Nathan Kline Institute, Orangeburg, NY;
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: National Institute of Mental Health, Bethesda, MD;
authors.forename: John
authors.initials: J
authors.lastname: Hsiao
authors.affiliation: David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA;
authors.forename: Alexander
authors.initials: A
authors.lastname: Kopelowicz
authors.affiliation: Columbia School of Medicine, University of Missouri, Columbia, MO;
authors.forename: John
authors.initials: J
authors.lastname: Lauriello
authors.affiliation: Harvard Medical School, Corrigan MH Center, Beth Israel Deaconess Medical Center, Boston, MA;
authors.forename: Theo
authors.initials: T
authors.lastname: Manschreck
authors.affiliation: Feinstein Institute for Medical Research, Zucker Hillside Hospital, Glen Oaks, NY;
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mendelowitz
authors.affiliation: Department of Psychiatry Research, University of Iowa Carver College of Medicine, Iowa City, IA;
authors.forename: Del D
authors.initials: del D
authors.lastname: Miller
authors.affiliation: National Institute of Mental Health, Bethesda, MD;
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Severe
authors.affiliation: Department of Anthropology, The University of Florida College of Medicine at Jacksonville, Jacksonville, FL;
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wilson
authors.affiliation: David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA;
authors.forename: Donna
authors.initials: D
authors.lastname: Ames
authors.affiliation: Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM;
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.affiliation: Health Science Center, University of Texas, San Antonio, TX.
authors.forename: Jim
authors.initials: J
authors.lastname: Mintz
authors.affiliation: Feinstein Institute for Medical Research, Zucker Hillside Hospital, Glen Oaks, NY;
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010359:Patient Readmission; D011618:Psychotic Disorders / Q000188:drug therapy*; D012008:Recurrence; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone
keywords: clinical trial design; negative symptoms; psychotic symptoms; relapse prevention; schizophrenia