One of the other major questions was: what happens if one allows individuals to undergo an extended period of time on placebo (ie, 4 months)? Will this impact response to pharmacotherapy? A second question was: is acute treatment of minor depression sufficient? Will individuals who respond acutely require continuation treatment, as is the case with major depressive disorder? Additionally, what is the course of untreated minor depression for individuals who participate Inhibitors,research,lifescience,medical in a trial? Are we placing these people at an increased risk or burden by their continued presence in the trial while
on placebo? In order to gather pilot data to begin to answer these questions, individuals who completed the initial 12 weeks of the trial entered a continuation phase. The randomization of individuals Inhibitors,research,lifescience,medical for the acute and continuation phase of the trial were performed at the initial point of randomization,
rather than a second re-randomization, after completion of the acute trial. Therefore, individuals in this trial were randomized both to an acute phase and maintenance treatment with either fluoxetine or placebo and to one of four Inhibitors,research,lifescience,medical continuation phase conditions: fluoxetine-fluoxetine, fluoxetine-placebo, placebo-placebo, or placebo-fluoxetine. Analysis of the continuation phase of the study Inhibitors,research,lifescience,medical was a find more priori specified to be exploratory, because we knew that sizes of the cells would not
be sufficient to answer these questions. There were several features during the analysis plan that were unique. First was the realization that minor depression was most likely a heterogeneous syndrome. Therefore, we acknowledged the need to investigate the relationship between minor depression and a previous history of major Inhibitors,research,lifescience,medical depressive disorder and dysthymia, and also the relationship between minor depression and a family history of psychiatric disorders. In an attempt to more thoroughly utilize the data that would be gathered in this study, we decided that a mixed enough regression model would be more powerful than a standard analysis of variance of statistical approach. However, since the random regression model is not as accepted in psychiatric literature, we specified in the initial data analysis plan that both types of analyses be performed. A third aspect of this study was the evaluation of the categorical end point (ie, full remission of symptoms and return of functioning), as well as the parametric end points. One can use the design of this trial in minor depression to address a number of the challenges that we had earlier identified. This trial is a good example of the type of consensus thinking process that can be used to enhance diagnostic rigor and assessment of severity of illness.