September 1, 2014 |

Scientific studies indicate that current medications target the wrong parts of the brain.

A new study is challenging the relationship between depression and an imbalance of serotonin levels in the brain, and brings into doubt how depression has been treated in the U.S. over the past 20 years.

Researchers at the John D. Dingell VA Medical Center and Wayne State University School of Medicine in Detroit have bred mice that cannot produce serotonin in their brains, which should theoretically make them always depressed. But researchers instead found that the mice showed no signs of depression, but instead acted aggressively and exhibited compulsive personality traits.

This study backs recent research that indicates that selective serotonin reuptake inhibitors, or SSRIs, may not be effective in lifting people out of depression. These commonly used antidepressants, such as Prozac, Paxil, Celexa, Zoloft, and Lexapro, are taken by some 10% of the U.S. population and nearly 25% of women between 40 and 60 years of age. More than 350 million people suffer from depression, according to the World Health Organization, and it is the leading cause of disability across the globe.

The study was published the journal ACS Chemical Neuroscience. Professor Donald Kuhn, the lead author of the study, set out to find what role, if any, serotonin played in depression. To do this, Kuhn and his associates bred mice that lacked the ability to produce serotonin in their brains, and ran a battery of behavioral tests on them.

In addition to being compulsive and extremely aggressive, the mice that could not produce serotonin showed no signs of depression-like symptoms. The researchers also found, to their surprise, that under stressful conditions, the serotonin-deficient mice behaved normally.

A subset of the mice that couldn’t produce serotonin were given antidepressant medications and they responded in a similar manner to them as did normal mice. Altogether, the study found that serotonin is not a major player in depression, and science should look elsewhere to identify other factors that might be involved. These results could greatly reshape depression research, say the authors, and shift the focus of the search for depression treatments.

The study joins others in directly challenging the notion that depression is related to lower levels of serotonin in the brain. One study has shown that some two-thirds of those who take SSRIs remain depressed while taking them, while another has even found them clinically insignificant.

Critics of common antidepressants claim that they’re not much better than a placebo, yet may still have unwanted side effects.

SSRIs started to become widely used in the 1980s. Their introduction was heralded by the psychiatric community as a new era where safer drugs that directly targeted the causes of depression would become the standard. SSRIs, however, aren’t more effective than the older antidepressants, such as tricyclics and monoamine oxidase inhibitors, but they are less toxic.
A study by the National Institute of Mental Health found that two out of three patients with depression don’t fully recover using antidepressants.

These results “are important because previously it was unclear just how effective (or ineffective) antidepressant medications are in patients seeking treatment in real-world settings,” said James Murrough, a research fellow at the Mount Sinai School of Medicine Mood and Anxiety Disorders Program.

[ThisWayOut]

interesting... also explains why ssri's help relieve aggression/anger issues in some people I know... something else to look into. thanks for the info.

[archipelago]

Interesting because I was just reading how SSRIs are considered for OCD and that didn't make sense to me intuitively since I still consider OCD an anxiety disorder although it has been shifted recently into its own category.

I think there has been a general sense that SSRIs are not magic and may little more effect than placebo for a while now. I'm not sure that I've ever come across the idea that that is the only intervention for depression. Usually therapy of some kind is also part of treatment.

It does help explain to me why stimulants and non-SSRIs have relieved my depression when SSRIs have done almost nothing. The brain is too complex; we are only vaguely understanding some of the processes. Most information about various medications freely admit that the mechanism is unknown, even for long-standing, effective medications.

[Hellion]

Originally Posted by archipelago

Interesting because I was just reading how SSRIs are considered for OCD and that didn't make sense to me intuitively since I still consider OCD an anxiety disorder although it has been shifted recently into its own category.

I think there has been a general sense that SSRIs are not magic and may little more effect than placebo for a while now. I'm not sure that I've ever come across the idea that that is the only intervention for depression. Usually therapy of some kind is also part of treatment.

It does help explain to me why stimulants and non-SSRIs have relieved my depression when SSRIs have done almost nothing. The brain is too complex; we are only vaguely understanding some of the processes. Most information about various medications freely admit that the mechanism is unknown, even for long-standing, effective medications.

I don't know if it had little more effect than a placebo I'd think it wouldn't have noticable side effects...I thought a placebo is something that does nothing and is based on the person thinking it will, so then they actually think it is. I mean perhaps SSRIs aren't the most helpful for depression, but if they where placebos they'd do nothing at all, and from what I understand they can make people feel different.

[ThisWayOut]

I recently saw a video suggesting that SSRI's merely assist in nerve pathway strengthening, thus help depression that way, but not in the way we had thought them to work in the past (by increasing seratonin levels in the brain)... It didn;t have sources though, so I am not sure how reliable it is...

[archipelago]

I probably overstated, but I do vaguely recall reading a study that tested this. I should have said "placebo effect," which is part of how people test medications though I don't know enough about the procedure to explain it. But the placebo effect is about the belief that something will help actually does help. In some cases, the effects of the placebo can be captured by brain imaging. So it does do something, but not because it is an active chemical. With anti-depressants, people in a study who received a placebo improved, but after the study when they were told it was a placebo they deteriorated. That's not exactly what I was referring to though. There is some sort of threshold that has to be reached for the effects of a medication to be considered to exceed the placebo effect and with anti-depressants I think there is a smaller difference than people expected.

[Altered Moment]

Clinical trials were run way after the drug companies studies and showed no better results than placebo. People don't know what they are getting and a certain percentage will have improved symptoms with placebo. They compare the two. Placebo effect is a real phenomenon so they have to compare. Placebo shows the power of the mind and belief and is little understood.

The problem with clinical trials is they only last six to eight weeks. A much larger study was done that recreated actually clinical real world conditions but didn't compare placebo. The results were much much better and the study lasted months not weeks. The STAR D.

The mouse study is one study that still has to be replicated but it is a big finding.

Other studies on genetically modified mice have shown improvement with AD's based on receptor sites and not one chemical. A different mechanism than the lower level of serotonin theory I believe.

Then there are the studies that show that AD's promote nerve growth in areas of the brain that are involved in depression. Hippocampus Amygdala.

The mechanism is not known for sure for AD's in living human brains. The drug companies theories could be wrong with synapses and repuptake. It is widely believed that mono amines and receptors do play a role.

The research quite some time ago already went in a different direction. It is focused on communication between the limbic system and pre frontal cortex and also a lot of focus on different receptor sites. Genetics is a big focus now with the hopes of tailor made drugs.

In the real world many people don't respond to SSRI's but many have great results. I have had unbelievable results with Fetzima SSNRI for six months. Night and day. Something is working and it ain't placebo.

How can they explain how they work for so many people.

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