Understanding Reuptake in Fibromyalgia and ME/CFS Drugs

Illustration of neurons firing

KTSDESIGN / Getty Images

When you're learning about treatment options for fibromyalgia and chronic fatigue syndrome, you're likely to come across the term "reuptake inhibitors." It describes a type of antidepressant that we're commonly prescribed, including the FDA-approved fibromyalgia medications Cymbalta (duloxetine) and Savella (milnacipran).

But do you understand what reuptake means? When you first start learning about reuptake inhibitors, it can be confusing—we know these conditions are believed to involve low levels of the brain chemicals serotonin and norepinephrine, so taking something that inhibits them sounds counterintuitive.

The explanation for this involves complex medical terminology that most of us are never going to understand. Below, you'll get a breakdown of this process in language that's easier to grasp.

What Is Reuptake?

First, a little bit about how your brain works:

Your brain cells (neurons) are separated by little gaps. When your brain transmits messages from one neuron to another, it bridges those gaps by releasing specialized chemicals called neurotransmitters to carry the message.

After a while, the space between the cells basically gets cluttered with a lot of used neurotransmitters. It's kind of like opening your mail and ending up with a pile of empty envelopes—the envelopes were important for getting the mail to you, but you no longer need them. Your brain cleans up the mess by reabsorbing the neurotransmitters so they can be recycled. The medical term for that is reuptake.

Now let's simplify it and go a step further:

Imagine a spider perched on the back of a dining-room chair. He wants to get to the table, so he shoots a strand of web across the gap. He shouldn't have a problem getting to his destination, but an oscillating fan across the room keeps turning that direction and blowing the web away before the spider can complete the journey.

Now, imagine that someone changes the speed on the fan so that it oscillates more slowly. That gives the spider enough time to cross the gap before the web is blown away.

The spider is the message, the web is the neurotransmitter, and the fan is reuptake. When you slow reuptake, the message has enough neurotransmitter to get where it's going. Reuptake inhibitors don't increase the total amount of neurotransmitter in your brain, but they do increase the amount of time it's available. That helps messages get where they're going.

How Reuptake Applies to Us

Researchers theorize that the brains of people with fibromyalgia, chronic fatigue syndrome, and many other neurological illnesses either have low levels of certain neurotransmitters or don't use their neurotransmitters properly. That's called neurotransmitter dysregulation, and it's believed to be responsible for many of our symptoms, including brain fog and pain amplification.

Research shows that slowing reuptake helps alleviate symptoms in a significant number of people with these illnesses.

Older reuptake inhibitors slowed the process for all neurotransmitters, which led to a lot of unwanted effects. Modern reuptake inhibitors selectively target specific neurotransmitters—especially serotonin and norepinephrine. They're called:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)

While these drugs cause fewer problems than the older medications, they still have a long list of side effects. Part of the problem is that we don't have neurotransmitter deficiencies in every area of the brain, so the medication may improve transmission in one area while disrupting it in another.

However, a new type of SSRI is emerging that may provide relief with fewer side effects by targeting the brain cell that receives a neurotransmitter's message. That cell is called a receptor, and each receptor is designed to only receive messages sent by certain neurotransmitters. Essentially, the receptor is a lock. Only the right chemical keys can open it.

This new drug uses simulated chemical keys to trick certain serotonin receptors into opening, making it easier for messages to flow from cell to cell. At least one drug of this type—Viibryd (vilazodone)—is currently approved for depression in the United States. (However, it has not been researched for either fibromyalgia or chronic fatigue syndrome.)

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  • 2008 University of Maryland Medical Center. All rights reserved. Chronic Fatigue Syndrome.

  • Goldstein, J. The Pathophysiology and Treatment of Chronic Fatigue Syndrome and Other Neurosomatic Disorders: Cognitive Therapy in a Pill. Alasbimn Journal 2000;2(7):AJ07-5.

  • Smith AK, et al. Genetic evaluation of the serotonergic system in chronic fatigue syndrome. Psychoneuroendocrinology. 2008;33(2):188-97.

  • Fields, R. Douglas, Ph.D. (2009) The Other Brain. New York: Simon & Schuster.

By Adrienne Dellwo
Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic.