title: Cost-effectiveness Analysis of Aripiprazole Once-Monthly for the Treatment of Schizophrenia in the UK.
abstract: BACKGROUND
  Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes.
  
  
  OBJECTIVE
  To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom.
  
  
  METHODS
  A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs.
  
  
  RESULTS
  The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000.
  
  
  CONCLUSIONS
  The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden.
  
  
  CONCLUSIONS
  Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics.
  
  
  CONCLUSIONS
  Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.
authors.forename: Michael
authors.initials: M
authors.lastname: Tempest
authors.forename: Christophe
authors.initials: C
authors.lastname: Sapin
authors.forename: Maud
authors.initials: M
authors.lastname: Beillat
authors.forename: Paul
authors.initials: P
authors.lastname: Robinson
authors.affiliation: Pharmerit International, Marten Meesweg 107., 3068 AV Rotterdam, Netherlands, mtreur@pharmerit.com.
authors.forename: Maarten
authors.initials: M
authors.lastname: Treur
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000191:economics*; D000068180:Aripiprazole / Q000008:administration & dosage* / Q000191:economics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000191:economics; D002908:Chronic Disease; D003024:Clozapine / Q000008:administration & dosage / Q000191:economics; D003198:Computer Simulation; D003362:Cost-Benefit Analysis / Q000191:economics*; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006801:Humans; D007273:Injections, Intramuscular; D008390:Markov Chains; D018803:Models, Economic; D000077152:Olanzapine; D000068882:Paliperidone Palmitate / Q000008:administration & dosage / Q000191:economics; D000069348:Quetiapine Fumarate / Q000008:administration & dosage / Q000191:economics; D018967:Risperidone / Q000008:administration & dosage / Q000191:economics; D012559:Schizophrenia / Q000188:drug therapy* / Q000191:economics*; D012565:Schizophrenic Psychology; D013222:State Medicine / Q000191:economics*; D006113:United Kingdom
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine; D000068882:Paliperidone Palmitate