Clinical and regulatory implications of active run-in phases in long-term studies for bipolar disorder
Article first published online: 30 NOV 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Acta Psychiatrica Scandinavica
Special Issue: “The Bipolar Maze: A Roadmap through Translational Psychopathology”, GUEST EDITOR Eduard Vieta
Volume 129, Issue 5, pages 328–342, May 2014
How to Cite
Clinical and regulatory implications of active run-in phases in long-term studies for bipolar disorder., , , .
- Issue published online: 15 APR 2014
- Article first published online: 30 NOV 2013
- Manuscript Accepted: 22 OCT 2013
- UK Medical Research Council
- UK Economic and Social Research Council
- National Institute for Health Research
- Stanley Medical Research Institute
- affective disorders;
- bipolar disorder;
- review of the literature
The integration of new treatments into the market and routine clinical practice should be dependent on robustness of evidence from randomised controlled trials (RCTs). We assessed study designs of long-term studies for bipolar disorder of all second-generation antipsychotics (SGAs) submitted to the Food and Drug Administration (FDA) and the completeness of evidence submitted to the regulatory agency.
Systematic review of double-blind RCTs comparing SGAs with placebo or active drugs in adults. FDA website and electronic databases were searched until July 2013.
Six placebo-controlled trials comparing aripiprazole, olanzapine, quetiapine and ziprasidone were found in the FDA website. Electronic searches found four additional RCTs about aripiprazole, olanzapine or quetiapine. All RCTs (either submitted to FDA or not) selected patients who responded to acute treatment to increase the treatment effect observed in the long-term phase (enrichment design). By contrast, in the prescribing information sheets for all SGAs, the reported indication was ‘maintenance treatment of bipolar disorder’.
Extrapolation of results from enrichment studies to the more general population of patients should be carried out cautiously because average treatment benefits are likely to be less in unselected patients. Clear guidance for regulatory submission of RCTs is needed.