One Dose of Antidepressant Changes Brain Connections, Study Says

Researchers eventually hope to predict who will respond to a drug and who won't

Thursday, September 18, 2014

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THURSDAY, Sept. 18, 2014 (HealthDay News) -- Just a single dose of a common antidepressant can quickly alter the way brain cells communicate with one another, early research suggests.

The findings, reported online Sept. 18 in Current Biology, are a step toward better understanding the brain's response to widely prescribed antidepressants. Experts said the hope is to eventually be able to predict which people with depression are likely to benefit from a drug -- and which people would fare better with a different option.

In a small study of healthy volunteers, researchers found that a single dose of the antidepressant escitalopram (Lexapro) seemed to temporarily reduce "connectivity" among clusters of brain cells in most regions of the brain.

The exceptions were two brain areas -- the cerebellum and thalamus -- where the drug boosted connectivity. In simple terms, connectivity refers to how brain cells "talk" to one another.

The cerebellum coordinates the body's voluntary movement, while the thalamus is involved in movement, sleep, and processing sensory information, including the things we see, hear and touch.

It's not clear yet what the findings could mean, said Dr. Radu Saveanu, a professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine in Florida.

But Saveanu, who wasn't involved in the study, said he sees it as an early step toward more "personalized medicine" for depression. In theory, brain scans could be used to predict a patient's likelihood of responding well to a given drug.

"Even though we have a large number of antidepressants available, we have no good way of predicting who'll respond to a medication," Saveanu said.

However, much research remains before brain scans could be used to guide anyone's treatment, he stressed. But the current study is a necessary first step, Saveanu said, because it looked at how one antidepressant dose affects depression-free people's brains.

Now some questions are, how do depressed people's brains respond? Are they different from people without depression? And how do people with depression differ from each other?

The study included 22 healthy adults who underwent functional MRI scans, which chart blood flow in the brain, giving an indication of the brain's electrical activity. Each study participant underwent three scans on separate days: a baseline scan; another done three hours after a dose of Lexapro; and a third done three hours after a dose of a placebo (inactive) pill.

Lexapro is a selective serotonin reuptake inhibitor (SSRI), a group of antidepressants that also includes brands like Paxil, Prozac and Zoloft. The drugs are widely prescribed, but no one knows precisely how they act on the brain.

It's been thought that they change the brain's connectivity, but that those effects probably take a few weeks to show up, said study researcher Dr. Julia Sacher, a fellow at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany.

"Our findings reveal that SSRIs affect brain connectivity right away, and that these changes encompass the entire brain," Sacher said.

It's possible, she added, that those changes are a first step in "remodeling" the brain before the drugs improve symptoms, which typically takes a few weeks -- if they work at all.

Sacher agreed that much work remains before these findings can prove useful in the real world. She said researchers still need to understand how different antidepressants affect the brains of people with and without depression -- not only after the first dose, but over the longer term, too.

The hope is to uncover distinct differences in brain connectivity between depression patients who ultimately respond to an antidepressant and those who don't.

Then, one idea would be to do a short brain scan before someone who is depressed starts treatment, Sacher said. "Ideally, the pattern of this baseline brain scan could provide psychiatrists with additional information on what kind of treatment would have the highest probability to help with the patient's symptoms," she said.

That's not feasible right now, she stressed, but in the future it could be.

Saveanu agreed. Functional MRI scans are noninvasive and take about 15 minutes. As the price comes down over time, Saveanu said, they might offer a viable way to help tailor depression patients' treatment.

SOURCES: Julia Sacher, M.D., Ph.D., fellow, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Radu Saveanu, M.D., professor, psychiatry and behavioral sciences, University of Miami Miller School of Medicine; Sept. 18, 2014, Current Biology, online

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