title: Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.
abstract: OBJECTIVE
  Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia.
  
  
  OBJECTIVE
  To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.
  
  
  METHODS
  A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014.
  
  
  METHODS
  A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training.
  
  
  METHODS
  Psychotic relapse and control of breakthrough psychotic symptoms.
  
  
  RESULTS
  Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ21 =11.1; P = .003) and control of breakthrough psychotic symptoms (β = 0.2; t79 = 2.1; P = .04).
  
  
  CONCLUSIONS
  The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00333177.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Subotnik
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: Laurie R
authors.initials: LR
authors.lastname: Casaus
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: Joseph
authors.initials: J
authors.lastname: Ventura
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: John S
authors.initials: JS
authors.lastname: Luo
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: Gerhard S
authors.initials: GS
authors.lastname: Hellemann
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles).
authors.forename: Denise
authors.initials: D
authors.lastname: Gretchen-Doorly
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles)2Department of Psychiatry, Veterans Affairs Greater Los Angeles Health.
authors.forename: Stephen
authors.initials: S
authors.lastname: Marder
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA (University of California, Los Angeles)3Department of Psychology, UCLA.
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D061345:Early Medical Intervention / Q000379:methods*; D005260:Female; D015438:Health Behavior; D006801:Humans; D008297:Male; D055118:Medication Adherence; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000517:prevention & control; D055502:Secondary Prevention / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone