Methodologic issues in maintenance therapy clinical trials
J. B. Greenhouse, D. Stangl, D. J. Kupfer and R. F. Prien
Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213-3890.
In the early 1980s, the National Institute of Mental Health supported a
multicenter, randomized, controlled, clinical trial on unipolar and bipolar
disorder to evaluate the comparative efficacies of lithium carbonate,
imipramine hydrochloride, a lithium-imipramine combination, and placebo in
preventing the recurrence of affective disorders. The objective of this
report is to present a reanalysis of the relative efficacies of these
treatments in patients with unipolar disorder to focus attention on general
issues related to the design and conduct of maintenance therapy trials. We
show that the earlier conclusions of that study that imipramine and the
combination therapy are more effective than lithium and placebo in
preventing the recurrence of depression in unipolar patients can be
accounted for by alternative explanations that are a consequence of the
design of the study. Our findings have important implications for the
design, conduct, and interpretation of results of maintenance therapy
clinical trials in general.
