title: Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry.
abstract: OBJECTIVE
  As psychopathology and social functioning can worsen with repeated psychotic episodes in schizophrenia, relapse prevention is critical. Because high nonadherence rates limit the efficacy of pharmacotherapy, the use of long-acting injectable (LAI) antipsychotics is considered an important treatment option. To date, many studies comparing LAIs and oral antipsychotics have been conducted; however, the results are mixed, and careful interpretation of the data is required.
  
  
  METHODS
  Selective review of existing literature regarding LAIs. We especially focused the discussion on the impact of the design of studies with different approaches comparing LAIs and oral antipsychotics in preventing relapse.
  
  
  RESULTS
  The results were diverse and were influenced by the design used, that is, randomized controlled trials (RCTs) showed LAIs and oral antipsychotics to have similar effects, whereas mirror-image and some large cohort studies showed LAIs to be superior to oral antipsychotics.
  
  
  CONCLUSIONS
  Divergent results from studies using different methodologies create a dilemma for comparative effectiveness research, and LAI studies may serve as an example of a situation in which a conventional RCT is not the gold standard. Traditional RCTs generally increase adherence compared with clinical practice and, therefore, might not be well suited to detect differences between LAIs and oral medications, because any increase in adherence affects patients on oral medications more than those on LAIs and thus leads to an underestimation of any potential difference in effectiveness. A possible solution would be the implementation of a true effectiveness trial in which post-randomization involvement would be kept to a minimum to better reflect routine practice.
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, 75-59 263 St, Glen Oaks, NY 11004, USA. psychiatry@nshs.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Taishiro
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage*; D015982:Bias; D015331:Cohort Studies; D057186:Comparative Effectiveness Research / Q000379:methods*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D018579:Patient Selection; D011570:Psychiatry; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D055502:Secondary Prevention; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
keywords: Antipsychotics; Depot; Long-acting injection; Mirror-image study; Randomized controlled study; Schizophrenia