Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)

• PANSS [ Time Frame: Jan 2016 ] [ Designated as safety issue: No ]
  Study consists of multiple components, each with their own objectives. For this (medication) component: number of patients in remission, based on PANSS scores (criteria of Andreasen et al.; 2005) after 4 weeks open label amisulpride, after 6 weeks double blind amisulpride or olanzapine and after 12 weeks of open label clozapine.
  
  
• Sellwood rating scale [ Time Frame: Jan 2016 ] [ Designated as safety issue: No ]
  Psychosocial intervention component, objective A: drug adherence rates as a function of (standardized self report and) Sellwood rating scales after 12 and 52 weeks.
  
  
• Biological profile [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  Biological predictors component, objective A: drug response (remission vs non-remission) as a function of biological profile, after 4 weeks, 10 weeks and 22 weeks (after each medication phase).
  
  
• MRS measures [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  Biological predictors component, objective B: using MRS scans, differences between responders and non-responders in regional glutamate levels a) at baseline and b) between baseline and after one month of treatment with amisulpiride.
  
  
• SOFAS global functioning [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  Psychosocial intervention component, objective B: drug adherence rates as a function of standardized global functioning (SOFAS score after 1 year) following psychosocial intervention vs treatment as usual.
  
  
• MRI assessments [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  MRI component objective: the percentage of first episode patients that show radiological abnormalities suggestive of neurological disorders which may explain the occurrence of psychotic symptoms - measurement at baseline only.
  
  

• All cause treatment discontinuation [ Time Frame: jan 2016 ] [ Designated as safety issue: Yes ]

  The different components of the study have their own secondary objectives:

  Medication component has multiple secondary objectives, most important one is all-cause treatment discontinuation after 4 weeks, 10 weeks and 22 weeks. Number and reason for premature discontinuations (treatment discontinuation) of the amisulpride and the olanzapine group will be compared (after 10 weeks).

  
  
• All cause discontinuation [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  Psychosocial intervention component has multiple secondary objectives, most important one is all-cause treatment discontinuation between treatment groups after 12 and 52 weeks.
  
  
• Biological markers [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  Biological predictors component has multiple secondary objectives, most important one is the ability of biological markers to predict response to antipsychotic and treatment tolerability in schizophrenia, after 4, 10 and 22 weeks.
  
  
• MRI assessments [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
  The ability of MRI to predict response to antipsychotic treatment in schizophrenia, after 4, 10 and 22 weeks.
  
  

Despite nearly fifty years of pharmacological and psychosocial research, the overall prognosis of schizophrenia has improved only marginally. While the efficacy of most antipsychotic medication is generally uncontested, their overall functional impact has been modest. In order to improve this unsatisfactory result, this study aims to optimize current treatments in schizophrenia and explore novel therapeutic options for schizophrenia. The study comprises a medication intervention component, a psychosocial intervention component, a biological predictor component and an MRI component. MRI assessments are performed at baseline, and used to determine whether potential organic causes for psychotic symptoms are present, and to test prospective value of these assessments for subsequent treatment response. MRI assessments of healthy volunteers will be included to test for deviations in patients' assessments; these volunteers will not participate in any other protocol procedure. The medication intervention component comprises a first 4-week phase of amisulpride treatment. Non-responders will subsequently be randomised to a 6-week double blind phase on either amisulpride or olanzapine. Patients who classify as non-responders at the end of this phase, a 12-week open label treatment with clozapine is initiated. Patients who classify as a responder in phase I, II or III, are drop outs or who are non-responders at the end of phase III flow to the psychosocial intervention component of the study. During this part, several interventions are tested, aimed to increase treatment compliance and keep patients on the medication to which they've responded well. Through the biological predictor component, it is determined whether glutamatergic markers predict response to first and second line treatments, and if an empirical combination of pharmacogenetic, proteomics- and metabolomic markers can provide clinical valuable predictive value.