Confirmation that there is a difference between Seroxat/Paxil and other SSRIs

A very topical subject this – it seems that Seroxat is actually different from other SSRIs… but I’m worried that it has come just too late.

Before you read this article please bear in mind that no-one actually knows just how SSRIs work – the hypothesis of chemical imbalance has been exposed as a lie.

However, what this new research does seem to point to is that Seroxat/Paxil acts in a different way to other SSRIs – perhaps this could explain why Seroxat/Paxil is so hard to stop taking?

The most widely prescribed antidepressants — medicines such as Prozac, Lexapro and Paxil — work by blocking the serotonin transporter, a brain protein that normally clears away the mood-regulating chemical serotonin. Or so the current thinking goes.

That theory about how selective serotonin reuptake inhibitors (SSRIs) work can now be put to the test with a new mouse model developed by neuroscientists at Vanderbilt University.

These mice, described in the online edition of the Proceedings of the National Academy of Sciences (PNAS), express a serotonin transporter that has been genetically altered so that it does not respond to many SSRIs or cocaine.

In addition to testing the theory about how SSRIs work, the new mouse model could lead to the development of entirely new classes of antidepressant medications, said Randy Blakely, Ph.D., Allan D. Bass Professor of Pharmacology and Psychiatry at Vanderbilt and senior author of the PNAS paper.

“Many antidepressants have been shown to target other proteins besides the serotonin transporter and … their efficacy in treating depression takes many weeks to develop,” Blakely said. “There is likely a lot that we don’t know about how these drugs act.”

To generate the mouse model, Blakely and colleagues at Vanderbilt and the University of Texas Health Science Center at San Antonio first determined exactly which parts of the serotonin transporter protein interact with SSRIs. They took advantage of the fact that the fruit fly expresses a serotonin transporter that is relatively insensitive to the drugs.

By changing the protein’s amino acid building blocks, they converted parts of the human serotonin transporter into its fruit fly equivalent, and in so doing identified the single amino acid required for potent binding to many SSRIs as well as to cocaine.

As predicted, the genetically-modified mice displayed normal serotonin transporter levels, and their transporter exhibited normal activity in clearing serotonin from the synapses between nerve cells. But the mice did not respond to Prozac or Lexapro, indicating that the transporter is indeed the specific target of these medications for blocking serotonin inactivation.

“Interestingly, one SSRI, paroxetine (Paxil), retains its normal powerful action on the transporter, revealing that — at a molecular level — different antidepressants interact with the transporter in different ways,” Blakely said.

The researchers are now evaluating chronic administration of SSRIs to determine how much the transporter contributes to the more clinically relevant, delayed effects of these drugs, as well as for the side effects experience with antidepressant medications.

Because the serotonin transporter in the mouse also lost cocaine sensitivity, the model also may help researchers determine exactly how cocaine acts in the brain. “Perhaps what started as a hunt for better ways to treat depression may also spill over into a better understanding of addiction,” Blakely said.

Brent Thompson, Ph.D., is the first author of the PNAS paper. Blakely directs the Center for Molecular Neuroscience and the Silvio O. Conte Center for Neuroscience Research at Vanderbilt.

Douglas McMahon, Ph.D., professor of Biological Sciences and Pharmacology at Vanderbilt, also collaborated on the research, which was supported by the National Institutes of Health.

Explaining the rise in antidepressant prescribing… or not?

Ben Goldacre pointed out this new research in the BMJ – Explaining the rise in antidepressant prescribing.

It seems the research shows that the rise in antidepressant prescribing is nothing to do with new prescriptions, rather it’s due to more people being on the drugs for longer “The rise in antidepressant prescribing is mainly explained by small changes in the proportion of patients receiving long term treatment.” [It should be noted that the research is 5 years out of date already as the years covered are 1993 – 2005].

Hmmmm.

If that’s the case, I wonder if any research has been done into possible harm due to long-term SSRI use – by Glaxo maybe? Or Pfizer perhaps?

I wonder if patients find, when they try to stop taking SSRIs, they can’t because they have become addicted to the drug?

From the research: “…A key question remains: if the changes in antidepressant prescribing are accounted for by changes in the proportions of those in receipt of long term prescriptions, does this represent appropriate prescribing for those with chronic and relapsing disease according to current guidance or does it arise from a failure to discontinue antidepressants in those with milder illness, or both?…”

But no mention of addiction.

A very important point to be made here is that all too often, SSRI withdrawal symptoms are wrongly diagnosed by doctors as the underlying disease returning – so they simply put the patient back onto the SSRI.

From the research again: “Antidepressant prescribing is much higher compared with 10 years ago. This increase is not because of an increase in the incidence of new cases of depression, a lower threshold for treatment, an increase in the proportion of new cases of depression for whom antidepressants are prescribed, or an increase in the duration of the prescriptions written for new cases of depression. Rather, the dramatic changes in antidepressant prescribing volumes between 1993 and 2005 seem to be largely because more patients are on long term medication and this group consumes the most drugs. In order to better understand the rise in antidepressant prescribing, research needs to focus on chronic prescribing and policy needs to focus on encouraging appropriate high quality monitoring and review of those patients who become established on long term prescriptions.”

And still no mention of addiction…

It seems to me that the researchers need to see beyond the simple pattern of prescribing and look to the real reasons behind the long term use of SSRIs.