DEPRESSION
December 6, 2013

A New Tool in the Antidepressant Toolbox?

Sarcosine, found in muscles and other body tissues, improved mood better than a popular antidepressant.

It may not be the next Prozac, but sarcosine, a substance found in muscles and other body tissues, is showing potential as a possible treatment for depression.

In a brief, six-week trial on depressed patients, sarcosine even outperformed the antidepressant citalopram (Celexa).

Sarcosine is a derivative of glycine, the smallest of the amino acids. It has previously shown to help patients with obsessive-compulsive disorder (OCD).

It may be that by simply changing the level of activity of the NMDA receptor sarcosine enhances neuroplasticity, the ability to remodel nerve networks in the brain.

Scientists believe sarcosine affects mood by enhancing the activity of NMDA receptors in the brain. These receptors help the brain adapt (plasticity) and are also involved in memory.

Forty patients diagnosed with major depressive disorder were randomly chosen to receive either sarcosine or citalopram for six weeks. Neither the patients nor their doctors knew which treatment they were prescribed.

Patients receiving sarcosine reported significantly improved mood scores, were more likely to experience relief of their depression symptoms, and were less likely to drop out of the study compared to those on citalopram. There were no major side effects in either group, but patients receiving sarcosine reported fewer minor problems than patients treated with citalopram.

One thing that puzzles researchers is that ketamine and synthetic drugs that mimic it are thought to ease depression by blocking the NMDA receptor, essentially de-activating it, the exact opposite of how sarcosine works.

How can activating and de-activating the same receptor both ease depression? That's not known yet but it's possible that NMDA receptor underactivity can cause depression in some people, while overactivity provokes it in other people.

The researchers also speculate that simply changing the level of activity of the NMDA receptor may enhance neuroplasticity, the ability to remodel nerve networks in the brain.

Sarcosine can be taken orally. And at least in this small trial, people who took it reported fewer side effects than those who took the approved depression drug, citalopram (Celexa).

It's been nearly three decades since the last truly new drugs to treat depression were developed. And while currently available antidepressants are the most common treatment for depression, they may increase the likelihood of depression recurring.

They also do not work for everyone, suggesting that drugs such as sarcosine, which affect different pathways, may have a role to play in helping ease the burden of depression.

An article on the study of sarcosine as antidepressant appears in Biological Psychiatry.

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