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.

KEYWORDS: :

• serotonin
• norepinephrine
• dopamine
• two week delay
• SSRI
• tricyclic antidepressant
• venlafaxine
• reboxetine