The most commonly prescribed antidepressants are Selective Serotonin Re-uptake Inhibitors (SSRIs). Skeptics argue that because it takes four to six weeks for these antidepressants to kick in, they don’t really work or that if they do, it’s not because the patient has low levels of serotonin in the brain.
Let’s start with a little background. Serotonin has multiple functions in the brain, one of which is keeping us calm and content. It is a neurotransmitter that works most effectively when it is outside of the brain’s neurons; although it doesn’t do anything good or bad if it is inside the brain’s cells. SSRIs work by blocking the serotonin transporter which results in more serotonin being outside of the neurons where it can do it’s job.
If there is too little serotonin active outside the brain’s cells, we become nervous, unhappy, or unable to feel any pleasure. By blocking the the transporter that inactivates serotonin, SSRIs can restore the brain’s active levels of serotonin returning us to a calm and content state. Skeptics of SSRI efficacy will return to the concept that the delayed effect means they don’t really work.
It is rather interesting that SSRIs don’t work after taking just one pill, especially considering that SSRIs are not the only drugs that block the serotonin transporter. Street drugs like cocaine and ecstasy also reportedly block the serotonin transporter. But it obviously does not take four to six weeks for cocaine and ecstasy to take effect.
Rather than assuming that the medication is not working, let’s consider an analogy. If you were to go to a dietitian to set up a meal plan to help you lose weight. You and your dietitian come up with a good plan that is likely to work. However, your refrigerator and kitchen are stocked with the items you already eat. Rather than wasting the food you’ve already purchased, you consume it and slowly begin restocking your kitchen with healthier items. Because of this transition time, your weight remains stable but about a month after you’ve begun, you start to lose weight. This is the time when the old foods in your kitchen have been replaced with healthier options.
More recent research suggests an analogous explanation of why SSRIs don’t kick in right away. The reason suggested is that SSRIs don’t target the serotonin transmitter directly. Although some SSRIs (like Lexapro) bind directly to the transporter, the direct binding is not the underlying mechanism of action. Instead antidepressants target our DNA, in particular the genes that code for the serotonin transporter. They make these genes less active causing there to be less transporter molecules available in the brain. This, the new research argues, explains the delayed action of antidepressants. As our brains already have plenty of transporter molecules when we begin taking antidepressants, it takes awhile for the suppression of genes coding for the transporter take effect in the brain.
When we start taking the medication, our brain is like the refrigerator, full of old food choices. It takes a few weeks to get through the old food and begin replacing it with healthier alternatives that can ultimately stabilize us and make use function normally.
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This article was originally posted on The Superhuman Mind by Berit Brogaard D.M.Sci., Ph.D.