Foundation-Supported Scientists Report Progress on Fast-Acting Antidepressants that also Reduce Anxiety

Denis J. David, Ph.D., expert on depression and anxiety
Denis J. David, Ph.D.

A team of investigators led by two-time NARSAD Distinguished Investigator Grantee René Hen, Ph.D., of Columbia University, and including 2010 NARSAD Young Investigator Grantee Denis J. David, Ph.D., in the lab of Alain Gardier, Ph.D., Pharm.D., University of Paris-Sud in France, report important progress on development of a medication that may rapidly alleviate the symptoms of depression and co-morbid anxiety.

The medication, known as RS67333, affects the brain serotonin neurotransmitter system by activating the serotonin-4 receptor (5-HT4). However, unlike commonly prescribed antidepressant medications such as Prozac®, Paxil®, and Celexa®—selective serotonin reuptake inhibitors (SSRIs) that target the serotonin transporter SERT—RS67333 shows a therapeutic effect in animal models of anxiety/depression after only seven days of treatment. By contrast, SSRIs usually take three to six weeks to display beneficial therapeutic effects, and many patients don’t respond at all.

Drs. Hen, David and colleagues report in a paper published online in the journal Neuropsychopharmacology on November 28th that RS67333, like Prozac®, has both antidepressant and anti-anxiety effects in an animal model of anxiety/depression. In addition, RS67333 stimulates neurogenesis in the hippocampus of the adult brain and facilitates maturation of newborn neurons.

Interestingly, the investigators also found that the beneficial effects of SSRIs on behavior and neurogenesis require activation of serotonin-4 receptors. Previously only serotonin-1A receptors (5-HT1A) were known to be necessary for the effects of SSRIs. Importantly, the authors find that the rapid-acting anti-anxiety effects of RS67333 are not dependent upon the birth of new neurons in the hippocampus. This is an exciting finding in the search for faster-acting antidepressant medications as some hypotheses suggest that the delay in the effects of SSRIs is due to the lag between the birth of new neurons and their maturation and integration into functional brain circuits, suggesting that RS67333 acts rapidly through a previously unknown mechanism of action.

The scientists note that RS67333 may have unwanted side effects in other peripheral tissues including the heart, gastrointestinal tract, and urinary bladder. However, targeting signaling molecules that interact with serotonin-4 receptor may be preferable to blockade of SERT when attempting to produce novel antidepressants with rapid therapeutic effects.

Read an abstract of the research paper.

Article comments

What a new idea !!!! How doing novelty with old concept...
Congratulations for the discovery.

This sounds promising, thinking back at all the antidepressants I've tried and waited for results. And as noted having trouble with them working at all. And if my anxiety could be helped also that would be a major plus. Keep up the good research.

Congratulations for this beautiful work.

When are they actually going to get a new med to market. I have no doubt that something will end up happening and nothing will come of this new drug. You would think with the amount of brain research in the last 10 years and optogenetics that there would be something on the horizon. Mentally ill sufferers who are treatment resistant need for more precise and effective drugs or brain stimulation brought in

Very encouraging news!
Very interested in further developments with this approach!
Keep up the great work!
There is HOPE for so many souls challenged with depression and/or major anxiety!
With Tremendous Gratitude,
Hopeful Heart

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