Why some antidepressants may initially worsen symptoms

December 17, 2014, Cell Press

New research helps explain a paradoxical effect of certain antidepressants—that they may actually worsen symptoms before helping patients feel better. The findings, highlighted in a paper publishing online December 17 in the Cell Press journal Trends in Cognitive Sciences, may help investigators fix the problem as well as create new classes of drugs to treat depression.

Selective reuptake inhibitors (SSRIs) are the most widely prescribed class of antidepressant drugs, and they work by increasing levels of a called serotonin. While this boost in serotonin occurs within minutes to hours after an SSRI is taken, patients usually have to take the medication for about 2 weeks before experiencing any relief of symptoms. During this delay, the drug may actually aggravate depression, in some cases even increasing the risk for suicide.

Researchers and clinicians have been puzzled by this, but Adrian Fischer of Otto-von-Guericke University in Germany and his colleagues now point to evidence from recent studies showing that serotonin neurons transmit a dual signal that consists of the release of serotonin as well as glutamate, another brain chemical. The investigators say that SSRIs may affect these two components of the dual signal in different ways.

"While the serotonergic component is immediately amplified following SSRI administration, the glutamate component is acutely suppressed and is only normalized after several days of drug treatment," says Fischer. He notes that the serotonin component of the dual signal has been linked to motivation, while the glutamate component has been linked to pleasure and learning. "These differential time courses may help to explain the paradox of acute versus chronic SSRI effects."

A better understanding of serotonin neurons' dual signal and its varied response to acute and chronic may help resolve some of the paradoxes observed with SSRIs. Delineating the contributing factors of each aspect of the dual signal may point to new drug targets for reducing the delay in effectiveness of SSRIs or even to completely new types of . Also, the discovery of the dual signal helps explain why the delayed onset of clinical efficacy that's seen with SSRIs is not evident with other that instead target glutamate receptors.

Explore further: Compound enhances SSRI antidepressant's effects in mice

More information: Dual serotonergic signals: a key to understanding paradoxical effects? Trends in Cognitive Sciences, 2014.

Related Stories

Compound enhances SSRI antidepressant's effects in mice

June 21, 2013
A synthetic compound is able to turn off "secondary" vacuum cleaners in the brain that take up serotonin, resulting in the "happy" chemical being more plentiful, scientists from the School of Medicine at The University of ...

Single dose of antidepressant changes the brain

September 18, 2014
A single dose of antidepressant is enough to produce dramatic changes in the functional architecture of the human brain. Brain scans taken of people before and after an acute dose of a commonly prescribed SSRI (serotonin ...

Can a genetic test help predict which antidepressant will be most effective?

December 8, 2014
Depression is the most commonly diagnosed mental illness, and antidepressants are the most frequently prescribed treatments for it. But with dozens of medications to choose from, and with individuals responding better to ...

Study questions link between antidepressants, miscarriage

September 9, 2014
(HealthDay)—Some studies have found that women who use common antidepressants early in pregnancy face a raised risk of miscarriage, but new research suggests the link might be better explained by the depression, rather ...

Increased risk of bleeding with combined use of SSRIs and antiplatelet therapy after heart attacks

September 26, 2011
Heart attack patients taking selective serotonin reuptake inhibitors (SSRIs) in combination with antiplatelet therapy -- acetylsalicylic acid (ASA), clopidogrel or both (dual antiplatelet therapy) -- are at higher risk of ...

Drugs for depression linked with failure of dental implants

September 12, 2014
A team from McGill University has discovered that people who take the most common antidepressants (such as Celexa, Paxil, Lexapro, Prozac, and Zoloft, the Selective Serotonin Reuptake Inhibitors or SSRIs) are twice as likely ...

Recommended for you

The connection between alcoholism and depression

September 21, 2018
Alcoholism and depression often go hand-in-hand.

Even toddlers weigh risks, rewards when making choices

September 21, 2018
Every day, adults conduct cost-benefit analyses in some form for decisions large and small, economic and personal: Bring a lunch or go out? Buy or rent? Remain single or start a family? All are balances of risk and reward.

Early warning sign of psychosis detected

September 21, 2018
Brains of people at risk of psychosis exhibit a pattern that can help predict whether they will go on to develop full-fledged schizophrenia, a new Yale-led study shows. The findings could help doctors begin early intervention ...

In depression the brain region for stress control is larger

September 20, 2018
Although depression is one of the leading psychiatric disorders in Germany, its cause remains unclear. A recent study at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in Leipzig, Germany, found ...

Quitting junk food produces similar withdrawal-type symptoms as drug addiction

September 20, 2018
If you plan to try and quit junk food, expect to suffer similar withdrawal-type symptoms—at least during the initial week—like addicts experience when they attempt to quit using drugs.

American girls read and write better than boys

September 20, 2018
As early as the fourth grade, girls perform better than boys on standardized tests in reading and writing, and as they get older that achievement gap widens even more, according to research published by the American Psychological ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.