title: Effect of prior treatment with antipsychotic long-acting injection on randomised clinical trial treatment outcomes.
abstract: BACKGROUND
  It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations.
  
  
  OBJECTIVE
  To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence.
  
  
  METHODS
  Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study).
  
  
  RESULTS
  Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA.
  
  
  CONCLUSIONS
  A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.
authors.affiliation: Centre for Mental Health, Imperial College, 37 Claybrook Road, London, UK. t.r.barnes@imperial.ac.uk
authors.forename: Thomas R E
authors.initials: TR
authors.lastname: Barnes
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Drake
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
authors.forename: Karen P
authors.initials: KP
authors.lastname: Hayhurst
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.forename: Shôn W
authors.initials: SW
authors.lastname: Lewis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D055118:Medication Adherence; D064792:Pragmatic Clinical Trials as Topic; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents