Randomised controlled trial of effect on quality of life of prescription of second generation (atypical) versus first generation antipsychotic drugs in schizophrenia [Abstract]

Objectives: To compare the class of conventional, first generation antipsychotic drugs (FGA) with the atypical, second generation drugs (SGA) other than Clozapine, in people with schizophrenia needing a change in treatment because of poor response or side effects. We hypothesized that SGA drugs would be associated with improvement in health-related quality of life. Design: A five-centre, RCT with three, blinded follow-up assessments over one year. The trial was conducted in general adult mental health settings in 14 NHS Trusts in Greater Manchester, Nottingham, Cambridge and London. Participants: 227 participants age 18-65 with schizophrenia and related disorders. Intervention: Random allocation to prescription from the class of SGA drugs, other than Clozapine, available at the time of the trial (Amisulpride, Olanzapine, Quetiapine, Risperidone) or to an FGA drug; choice of drug from within the randomised class was made by the managing clinician. Main Outcome Measures: The primary outcome was the Quality of Life Scale (QLS). Secondary outcomes included symptoms (PANSS), side effects and participant satisfaction. Results: The primary hypothesis of a five point improvement in QLS over the year following commencement of SGA compared with FGA drugs was excluded by an intention to treat analysis. Participants in the FGA arm showed a trend towards greater improvements in QLS and symptoms scores, suggesting failure to find the predicted advantage for SGA drugs was unlikely to be due to low statistical power (75%). Participants reported no clear preference for either class of drug. Conclusion: In people with schizophrenia whose medication is being changed because of intolerance or broadly-defined ineffectiveness, there is no disadvantage over one year in terms of quality of life, symptoms or associated costs of care in commencing conventional FGA drugs rather than atypical SGA drugs. This result is not accounted for by inadequate power or by patterns of drug discontinuation.