Is the bell-shaped dose-response curve of the selective serotonin reuptake inhibitor due to 5-HT auto-receptors?

A dose-response curve is a plot of drug efficacy versus dose. Interestingly, some antidepressants show a bell-shaped dose-response curve where increasing dose leads to increasing efficacy only up to a point, whereupon further increases lead to decreasing efficacy. Here, we propose that the first part of the curve reflects the basic, uncomplicated dose-response relationship of these antidepressants whereas the second, decreasing part remains to be explained. Our hypothesis is that a negative feedback pathway through 5-HT auto-receptors decreases the efficacy of selective serotonin reuptake inhibitors with increasing dose, thereby creating the second, anomalous part of the dose-response curve. This effect can also account for the so-called therapeutic window of such antidepressants.