Though there were a lot of interesting stories in the news this week, the most interesting one seems to have been published without anyone in the media noticing it.
As reported in The Journal of Neuroscience,scientists seem to have finally discovered how Prozac really works.
For years the drug companies have been explaining that Prozac and other SSRI antidepressants work by raising serotonin levels in the brain, though this hypothesis was never well-supported by research, even though it was used very heavily in the marketing of these drugs.
Now, decades after this drug was prescribed to millions of people, researchers have learned that what Prozac really does is to stimulate the growth of new neurons in the hippocampus, the portion of the brain that, among other things, regulates how new information is stored in the brain and which, when it is damaged, produces dementia.
In some elegantly constructed rodent experiments the researchers showed that Prozac lessened the anxiety of mice given the drugs when compared to that of controls, and that it did so after the same time delay that humans experience before they respond to an SSRI drug.
Sure enough, when they looked at the brains of the mice who displayed the dramatic change in behavior, they saw that the change correlated with the growth of new neurons in their hippocampi.
Then the scientists irradiated the mouse brains in a way that prevented the growth of new neurons after taking the drug. Though their serotonin levels increased, these mice remained anxious, and on autopsy it was seen that indeed they hadn't grown those new neurons. Unless those new neurons grew in the hippocampus, the mice stayed "depressed".
What should make anyone not taking a drug that has modified how they store new information feel a lot of anxiety is the realization that it has taken almost 30 years after Prozac was approved by the FDA for anyone to investigate what it is really doing to the brain in a way that gives a valid answer. And what is even more worrisome is that the answer is one that should make any reasonable person ask, "Does anyone here have any clue what happens longterm when you continually stimulate the growth of new neurons in the part of the brain most closely associated with dementia?"
This brings home to me just how dangerous it is to take a drug year in and year out whose mechanism is not understood.
The general public has a touching but completely misguided trust that the drug approval process ensures their safety when they take a new drug. But what most people don't understand is that all the drug approval process ensures is that the new drug has some effect--however small--compared with a placebo and that it doesn't cause major organ failure or fast growing cancers during the period of up to two years that the typical drug approval trial lasts.
There's no requirement that the long term effects of the drug be monitored in any meaningful way. And there is certainly no requirement that research be done to illuminate exactly what the drug is doing to the body.
That is why it took about 12 years after the release of Avandia and Actos for scientists to get around to noticing that these drugs actually work by turning the stem cells that should turn into bone cells into baby fat cells instead, which over the long term causes serious ostoporosis leading to fractures.
This failure to investigate how drugs really work is why only now, decades after statins became the most heavily promoted drugs in history, evidence is accumulating that whatever impact these drugs have on heart disease--which turns out to be not much except in men under 56 with previous heart attacks--they appear work NOT by lowering LDL cholesterol, but by fighting inflammation.
This should make all of us think twice before taking any new drug, no matter how effective it is at doing what it is being sold (and tested) to do.
Before you add a new drug to your daily regimen, remind yourself that the explanation of how the drug achieves its effect printed in the drug's official Prescribing Information is probably nothing more than a guess. It might be decades until the actual effect that a powerful new drug has on the many interrelated systems of your body comes to light.
Scientists still don't fully understand how Metformin works, and it has been around for decades. What they are learning about the impact of TZD drugs, Avandia and Actos, on bone growth should make any thinking person give them a wide berth. The effect of inhibiting DPP-4, as Januvia and Galvus do, on anything but blood sugar levels has yet to be explored, though it is clear the enzyme in question is used all over the body, especially in the immune system. Even the long term impact of using insulin analogs which contain chains of amino acids that differ subtly from those of the insulin our body produces is a complete mystery.
As a scientist quoted in the article about the effect of Prozac on the brain says, "We still don't know, of all the effects Prozac has on young neurons, which ones are important." Another adds, "We need these leads to understand the cellular and circuit changes that occur with chronic drug administration to learn what the entire system is doing,"
Yes. We do. As we need to learn more about what every drug that millions of people are taking every day, year in and year out is doing.
Though you might want to take a drug that decreases your anxiety before you read the studies that answer those questions. . . .
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