Abstract
One important aim of the recent reorganization of the National Institute of Mental
Health (NIMH) is to streamline the development of new treatments for patients with
severe mental illnesses, such as bipolar disorder. Researching new treatments for
patients with bipolar disorder presents specific problems not readily addressed by
traditional efficacy trial methodologies that aim to maximize internal validity. This
article reexamines several assumptions that have guided the design of these efficacy
trials but that also create obstacles for studies of bipolar disorder and suggests
potential solutions. This article draws on literature from neurology and psychiatry
and discussions at a MacArthur Foundation–sponsored Conference on Longitudinal Methodology
in 1992 (David J. Kupfer, M.D., Chair), which brought together investigators to consider
alternative designs for patients with severe and persistent mental illness. In addition,
we benefited from discussions at two NIMH-sponsored conferences, one held in 1989
(
Prien and Potter 1990
) and the other in 1994 (
Prien and Rush 1996
), at which investigators and methodologists discussed issues surrounding the development
and conduct of informative efficacy trials for patients with bipolar disorder. Based
on these discussions and recent literature reviews, we 1) outline common problems
in the development and evaluation of effective acute treatments for bipolar disorder
and 2) suggest possible solutions to these impediments. We also discuss alternative
designs by which to build a sequence of acute treatment studies from which efficacy,
safety, and the comparative value of different treatments can be established.Keywords
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Article info
Publication history
Accepted:
April 4,
2000
Received in revised form:
March 29,
2000
Received:
January 4,
2000
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
