Instant Antidepressants on the Horizon




Packs of pills

Depression and similar mental disorders like bi-polar disorder, anxiety, and obsessive–compulsive disorder are associated with imbalances in neurotransmitters in the brain. Neurotransmitters are signaling molecules exchanged between neurons (nerve cells) for communication purposes. One of these neurotransmitters is serotonin, and drugs that increase serotonin levels in the brain are the most widely used treatments for depression and similar conditions. Nevertheless, these drugs are not unproblematic as many patients get frustrated as it can take several weeks after taking them, before the drugs become effective, in some patients, the drugs work don’t work at all, and in others, the side effects of these drugs can be a huge problem.

The molecules in the brain to which serotonin binds to deliver its signal, are called serotonin receptors. There are seven families of serotonin receptors known and each family has a different function; some of them even have opposite effects. Conventional anti-depressants increase serotonin levels in all parts of the brain and make no difference which serotonin receptors are present in the areas they affect. A better understanding which serotonin receptor is responsible for anti-depressive and anxiety-reducing effects of serotonin could lead to the development of medications that specifically target these receptors and therefore reduce side effects and increase efficacy of the treatment compared to the current “shot-gun” approach.

In a recent publication in the journal Proceedings of the National Academy of Science (PNAS), scientists have come one step closer to this ideal. They showed that increasing the activity of the serotonin receptor 5HT1A leads to a decrease of behavior in mice that is linked to depression and anxiety. 5HT1A is a member of the 5HT1-family of serotonin receptors that is located on the cell surface of certain neurons (nerve cells) that receive serotonin signals. The signal is transmitted into the neuron by another molecule, called a G-protein which is hooked to the 5HT1A-receptor on the inside of the cell membrane. The activity of this G-protein can be turned down by another protein called a regulator of G-protein signaling (RGS).

In the publication, the researchers reported about mice in which the RGS cannot turn down the G-protein’s activity due to a mutation in the G-protein. These mice showed behaviors without being given any drugs that are usually seen when antidepressants are given to mice. These mice also reacted much stronger when they were given serotonin-increasing antidepressants when compared to control mice that did not have the mutation. These finding show that the RGS protein plays an important part in decreasing the anti-depressant effect of the 5HT1A receptor. A future medication that selectively inhibits the action of the RGS protein might be a more effective treatment for depression and related conditions, with the risk of fewer side effects compared to the current unspecific serotonin-enhancing drugs.

Reference

Talbot JN, Jutkiewicz EM, Graves SM, Clemans CF, Nicol MR, Mortensen RM, Huang X, Neubig RR, & Traynor JR (2010). RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects. Proceedings of the National Academy of Sciences of the United States of America, 107 (24), 11086-91 PMID: 20534514

  • http://disgruntledphd.blogspot.com disgruntledphd

    Without getting into the specifics of the PNAS paper, there is a lot of evidence that much of the efficacy of SSRI’s is due to a placebo effect. See Kirsch 2002, Kirsch & Sapirstein 1999. A meta-analysis in the Lancet ( i think) suggested that only the most severly depressed patients gained more from the active drug than a placebo. In light of this, I personally wouldn’t hold my breath on any form of SSRI having efficacy above placebo (well, they’ll probably work for a few years, then peter out, like most unsuccessful therapies throughout history).

    • http://www.ce-psychology.com/psychopharm.html Debra Stang

      I think the media got a little carried away when they claimed that SSRIs work mainly due to the placebo effect. There were several factors they didn’t consider.

      John Preston, of Alliant International University, discusses some of the ways that the media over-simplified the findings of the studies in the newsfeed below. It only takes a few minutes of your time, and it’s pretty interesting to watch.

      http://uofthenet.org/alliant/Psychopharm/Doantidepressantswork.html

      As for instant anti-depressants, I hope they do become a reality. I hate it that clients have to wait so long to see the effect of the anti-depressants available today. So many of my clients simply give up and stop taking them when there’s no improvement in a week or so…

      Debra Stang
      Alliant Professional Networking Specialist

  • http://www.theemotionmachine.com Steven

    “Instant antidepressants” sounds a little over-promising…unless you are referring to ecstasy (which I believe does increase serotonin, although I am not sure which kind). Although, admittedly, the anti-depression is short lived. We have to be extra careful of withdrawal effects on these kinds of drugs and dependency issues, including abuse. Great article though!

Sandra Reichstetter, PhD

Sandra Reichstetter, PhD, studied Biology at the Technical University in Darmstadt with a major focus on Zoology and Biochemistry and earned her PhD in Immunology and Genetics at the University of Erlangen-Nuremberg. After a Postdoctoral Fellowship at the Benaroya Research Insitute in Seattle that focused on the immune response seen in Type 1 Diabetes, she started working in a biotech startup, where she is still working today.
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