Amisulpride augmentation in clozapine-unresponsive schizophrenia

• Research type

  Research Study

• Full title

  A multi-centre, double-blind, individually randomised, placebo-controlled, parallel arm RCT with 12-week follow-up to establish the clinical and cost effectiveness of amisulpride augmentation of clozapine in treatment-resistant schizophrenia unresponsive to clozapine

• IRAS ID

  56454

• Contact name

  Thomas Barnes

• Sponsor organisation

  Imperial College London

• Eudract number

  2010-018963-40

• ISRCTN Number

  ISRCTN68824876

• Research summary

  A 12-week, placebo-controlled, randomised controlled trial, to be conducted in secondary care mental health services, at four UK centres. The health technology to be assessed is the augmentation of clozapine treatment with another second-generation antipsychotic, amisulpride, in people whose illness has proved to be unresponsive to clozapine alone. The randomly assigned treatment regimens will be either 400mg amisulpride or 1 matching placebo capsule for the first 4 weeks, then the option of titrating up to 800mg amisulpride or 2 matching placebo capsules for the remaining 8 weeks. The study will be double-blind, with medication supplied as identical capsules containing either 400mg amisulpride or placebo. The optimum dose of clozapine at entry and subsequent augmentation will be achieved through a flexible dosing regimen whereby treating psychiatrists will be able to flexibly alter dose regimens to maximise clinical risk-benefit ratios. The primary outcome measure will be the proportion of ??responders?? using a criterion response threshold of a 20% reduction in mental state scale score, i.e. total score on the Positive and Negative Syndrome Scale (PANSS: Kay et al 1987, 1988). Therapeutic improvement will also be assessed in terms of broader, clinically-relevant outcome measures of social and occupational function and target symptoms and/or behaviours as well as overall health status and utility. Any direct pharmacokinetic effect on clozapine levels will be assessed by pre- and post-augmentation plasma levels of clozapine, samples being taken at baseline and at the end of the 12 weeks. Side effects will be systematically assessed. The costs and outcomes to allow for a cost effectiveness acceptability and net benefit analysis will also be measured.

• REC name

  London - Fulham Research Ethics Committee

• REC reference

  10/H0711/75

• Date of REC Opinion

  23 Sep 2010

• REC opinion

  Favourable Opinion