title: Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: a randomized trial.
abstract: OBJECTIVE
  Alcohol use disorders worsen the course of schizophrenia. Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia, risperidone does not. We have proposed that risperidone's relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use. Since long-acting injectable (LAI) risperidone both results in lower average steady-state plasma concentrations than oral risperidone (with lower D2 receptor occupancy) and encourages adherence, it may be more likely to decrease heavy alcohol use (days per week of drinking 5 or more drinks per day) than oral risperidone.
  
  
  METHODS
  Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were randomized to 6 months of oral or LAI risperidone between 2005 and 2008. Explanatory (efficacy) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions (in contrast to real-world settings), with intent-to-treat analyses being secondary.
  
  
  RESULTS
  Explanatory analyses showed that heavy drinking in the oral group worsened over time (P = .024) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups (P = .054). Furthermore, the 2 groups differed in the mean number of drinking days per week (P = .035). The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses (P = .018). Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale. The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI (P < .05), despite their significantly (overall) better treatment adherence (P < .005).
  
  
  CONCLUSIONS
  For the population considered here, schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone. Nonetheless, our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00130923.
authors: One Medical Center Drive, HB 7750, Lebanon, NH 03756 alan.i.green@dartmouth.edu.
authors: Alan I
authors: AI
authors: Green
authors: Mary F
authors: MF
authors: Brunette
authors: Ree
authors: R
authors: Dawson
authors: Peter
authors: P
authors: Buckley
authors: Amy E
authors: AE
authors: Wallace
authors: Hisham
authors: H
authors: Hafez
authors: Marvin
authors: M
authors: Herz
authors: Meera
authors: M
authors: Narasimhan
authors: Douglas L
authors: DL
authors: Noordsy
authors: Christopher
authors: C
authors: O'Keefe
authors: Roger W
authors: RW
authors: Sommi
authors: Richard M
authors: RM
authors: Steinbook
authors: Marjorie
authors: M
authors: Weeks
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone