One of the most problematic things for the severely depressed and suicidal is the fact that currently existing antidepressants are often slow to work, taking several weeks to exert their depression-relieving effects. Further complicating treatment is the fact that not every patient will respond to any given antidepressant. A person may have to patiently suffer through numerous weeks-long drug trials in order to find a drug – or a combination of drugs – that is most effective for his own case. Currently, there are only two known drugs which can rapidly relieve depression: scopolamine and ketamine. Unfortunately, neither of these drugs is suitable for use, due to their side effects. If a faster-acting antidepressant with a favorable side effects profile could be developed, it would be a real boon for those with depression.
Now, some University of Chicago researchers say they may have discovered just such an antidepressant.
In order to develop the antidepressant, a team of researchers led by Dr. Stephanie Dulawa, an associate professor of psychiatry and behavioral neuroscience at the University of Chicago, decided to investigate biological pathways which have been shown to work as antidepressants, but have never been studied for how quickly they take effect. In their search, they looked at different subtypes of receptors for serotonin, a chemical produced in the brain which has been shown to be linked to mood regulation. Many currently existing antidepressants already target serotonin, attempting to make more of it available in the brain.
When they examined the various receptor subtypes, one type in particular stood out from the rest: 2C receptors. When these receptor sites were blocked in mice, there was a significant reduction in depression symptoms within about five days. In contrast, it took at least two weeks for a control antidepressant to have any effect on symptoms.
According to study lead author Mark Opal, who is a graduate student at the University of Chicago, blocking these receptor sites may have actually worked even sooner, but they did not begin making measurements until the fifth day.
The research team says that normally serotonin 2C receptors inhibit the release of dopamine, another substance which is also believed to affect mood. Because of this, the team believes that when these receptors are blocked more dopamine is probably released into regions of the brain such as the prefrontal cortex. This region of the brain is believed to play some role in depression, although it is not yet well-understood what it might be.
According to Dulawa, drugs which can target this new biological mechanism may have great promise as fast-acting antidepressants. Some currently available antidepressants do already target this receptor, she says, but not exclusively. She and her team are now looking at various 2C inhibitors which might be suitable for human clinical trials.
The paper discussing the team’s work was published on October 29, 2013 in the journal Molecular Psychiatry.
Written by: Nancy Schimelpfening