title: Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs.
abstract: OBJECTIVE
  Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs.
  
  
  METHODS
  A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or all-cause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol.
  
  
  METHODS
  Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons.
  
  
  METHODS
  Age- and gender-adjusted risk ratios (RRs) (depot/oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs.
  
  
  RESULTS
  Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively.
  
  
  CONCLUSIONS
  The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.
authors.affiliation: Analysis Group, Inc, 111 Huntington Ave, 10th Fl, Boston, MA 02199, USA. nkirson@analysisgroup.com
authors.forename: Noam Y
authors.initials: NY
authors.lastname: Kirson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Weiden
authors.forename: Sander
authors.initials: S
authors.lastname: Yermakov
authors.forename: Wayne
authors.initials: W
authors.lastname: Huang
authors.forename: Thomas
authors.initials: T
authors.lastname: Samuelson
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Offord
authors.forename: Paul E
authors.initials: PE
authors.lastname: Greenberg
authors.forename: Bruce J O
authors.initials: BJ
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D006801:Humans; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations