Forbearance for fluoxetine: Do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?

Abstract

It is of high clinical interest to better understand the timecourse through which psychiatric drugs produce their beneficial effects. While a rough estimate of the time lag between initiating monoaminergic antidepressant therapy and the onset of therapeutic effect in depressed subjects is two weeks, much less is known about when these drugs reach maximum effect. This paper briefly examines studies that directly address this question through long-term antidepressant administration to humans, while also putting forth a simple theoretical approach for estimating the time required for monoaminergic antidepressants to reach maximum therapeutic effect in humans. The theory invokes a comparison between speed of antidepressant drug response in humans and in rodents, focusing on the apparently greater speed in rodents. The principal argument is one of proportions, comparing earliest effects of these drugs in rodents and humans, versus their time to reach maximum effect in these organisms. If the proportionality hypothesis is even coarsely accurate, then applying these values or to some degree their ranges to the hypothesis, may suggest that monoaminergic antidepressants require a number of years to reach maximum effect in humans, at least in some individuals.

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs

“…This is why fluoxetine is not suggested as a first-line treatment for migraine prophylaxis (European Federation of Neurological Societies (EFNS), American Academy of Neurology (AAN) practice guidelines). Nevertheless, the use of fluoxetine in migraine prophylaxis cannot be categorically excluded (23,43), and our study could, to some extent, explain its potential prophylactic action by shedding further light on the possible mechanism(s) involved. Our study is based on two seminal findings not specifically confirmed in this research, namely, that: (i) chronic fluoxetine increases central levels of 5-HT (44,45), although we tried somehow to mimic this effect by i.t. administration of 5-HT; and (ii) intracarotid infusions of capsaicin result in porcine carotid vasodilatation mediated by release of CGRP (16), a vasodilator neuropeptide released from capsaicin-sensitive trigeminal sensory nerves (10).…”

“…Our study is based on two seminal findings not specifically confirmed in this research, namely, that: (i) chronic fluoxetine increases central levels of 5-HT (44,45), although we tried somehow to mimic this effect by i.t. administration of 5-HT; and (ii) intracarotid infusions of capsaicin result in porcine carotid vasodilatation mediated by release of CGRP (16), a vasodilator neuropeptide released from capsaicin-sensitive trigeminal sensory nerves (10).…”