Recovery From Depressive Illness Does Fit an Exponential Model

Abstract

A very large number of therapeutic trials of antidepressant drugs have been reported in the scientific literature. Until now, the comparison of one drug with another, or with placebo, has been performed typically by comparing the scores on depression rating scales of the two groups of patients at fixed points of time after the beginning of therapy. It was postulated in 1989 that the curves of the recovery scores followed an exponential curve of the formula y = ae-bx + c. This hypothesis was tested in a double-blind controlled trial of the antidepressant minaprine, with the use of the scores on the Hamilton Rating Scale for Depression (HAM-D). We found that the correlation coefficient, Pearson's r, between the log of the HAM-D value and the week number of the study was -0.99. This gives a coefficient of determination of 0.98, which makes it clear that the model adequately fits the data. We conclude that the use of the formula gives a method of testing the statistical significance of the difference between treatments as a valuable alternative to traditional tests. We believe that this would give a much more sensitive discrimination between treatments because all of the data points are used to calculate a single parameter--the slope of the curve.

Efficacy and Tolerability of Hypericum Extract WS 5572 versus Placebo in Mildly to Moderately Depressed Patients - A randomized double-blind multicenter clinical trial -

“…However, comparison with published data also supports our claim of the clinical relevance of our findings. Priest and co-workers [23] specify the upper limit of a¸normal range for the total score of the 17-item HAMD (when the scale is filled in for patients who do not suffer from depression) as approximately 10 points. At the end of the treatment program, the HAMD total score mean and median in the Hypericum group had fallen below this upper limit, which was not the case in the placebo group.…”

“…Recent work by Priest et al [23] and by Friede et al [9] has shown that the time course of the HAMD total score during recovery from depression can be described by fitting an exponential regression model to the data. While such models can describe the data actually observed during a trial, they may also be used to predict the future recovery process beyond the end of the period of observation.…”

Rapid onset of true antidepressant action

“…1). For example, it has been reported previously that the changes in depression rating scale scores over time for treated and control groups can be well fit with logarithmic curve [11]. More recently, the NEMESIS study from the Netherlands studied a community sample in which there were 250 new episodes of major depression.…”

Modeling the Recovery from Depressive Illness by an Exponential Model with Mixed Effects

“…Priest et al [2] proposed to fit an exponential model to the mean scores of the treatment groups by:…”

“…The constant ␤ 3 has to be specified in advance, because otherwise it is not possible to estimate the regression equation for y'(t) . Priest et al [2] proposed to choose arbitrarily ␤ 3 = 5, because different studies with active treatments have shown that the HAM-D is less than 10 after 6 weeks, due to some background of depressive symptoms even in the "healthy" population, and it is higher than 0 by definition of the HAM-D scale. Priest et al concluded to take an arbitrary value between 0 and 10 for the score after complete recovery.…”