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Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.

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Irving Kirsch offered the above information in a publication obtained from the US National Library of Medicine. He is the Associate Director of the Program in Placebo Studies and a Lecturer in Medicine at Harvard Medical School. He is also Professor Emeritus of Psychology at the Universities of Hull and Plymouth in the United Kingdom, and a few others in the United States.  Needless to say, he’s done a lot of research, and his revelations above should be read by anybody taking, or considering taking, antidepressant drugs.

The Effectiveness of Anti-Depressant Drugs Compared To Placebo

In a 2002 study conducted by Kirsch and his team of researchers, published in The American Psychological Association’s Prevention & Treatment, it was discovered that 80 percent of the effect of antidepressants, as measured in clinical trials, could be attributed to the placebo effect. The difference between the response of the drugs and the response of the placebo was less than two points on average on a clinical scale that goes from fifty to sixty points. This is a very small difference, and is, according Kirsch, clinically meaningless:

I assumed that antidepressants were effective. As a psychotherapist, I sometimes referred my severely depressed clients for prescriptions of antidepressant drugs. Sometimes the condition of my clients improved when they began taking antidepressants; sometimes it did not. When it did, I assumed it was the effect of the drug that was making them better. Given my long standing interest in the placebo effect, I should have known better, but back then I did not.

Analyzing the data we had found, we were not surprised to find a substantial placebo effect on depression. What surprised us was how small the drug effect was. Seventy-five percent of the improvement in the drug group also occurred when people were give dummy pills with no active ingredient in them.  (source)

The response from critics was harsh, who emphasized that antidepressants have been evaluated in many trials and their effectiveness well documented.

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“Unpublished Data That That Were Hidden By Drug Companies”

The idea that scientific literature has firmly established the benefits of antidepressants has lost all credibility, thanks in large part to Kirsch and his team. They used the Freedom of Information Act to request that the Food and Drug  Administration (FDA) send data that pharmaceutical companies had sent to it for the process of obtaining approval for multiple antidepressants, which accounted for the bulk of antidepressant prescriptions at the time.  As a result, the researchers were able to obtain data on both published and unpublished trials:

 This turned out to be very important. Almost half of the clinical trials sponsored by the drug companies have not been published (Melander, Ahlqvist-Rastad, Meijer, & Beermann, 2003Turner, Matthews, Linardatos, Tell, & Rosenthal, 2008). The results of the unpublished trials were known only to the drug companies and the FDA, and most of them failed to find a significant benefit of drug over placebo. . . .  [T]he data in the FDA files were the basis upon which the medications were approved. In that sense they have a privileged status. If there is anything wrong with those trials, the medications should not have been approved in the first place. (source)

All in all, the data sent to the researchers by the FDA showed that only 43% of the trials showed a statistically significant  benefit of drug over placebo. The remaining 57% were failed or negative trials.

Many other studies have also demonstrated just how ineffective antidepressants are, as well as how often that fact is obscured by pharmaceutical companies. What’s worse, studies have since determined that anti-depressants can cause real harm to those who take them, and this information is often withheld, too. For example, a study published in The British Medical Journal by researchers at the Nordic Cochrane Center in Copenhagen revealed that pharmaceutical companies were not disclosing all information regarding the results of their drug trials. Researchers looked at documents from 70 different double-blind, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) and found that the full extent of serious harm in clinical study reports went unreported. These are the reports sent to major health authorities like the U.S. Food and Drug Administration.

Tamang Sharma, a PhD student at Cochrane and Lead Author of the study, noted that they “found that a lot of the appendices were often only available upon request to the authorities, and the authorities had never requested them,” revealing that she was “actually kind of scared about how bad the actual situation would be if [they] had the complete data.”

Joanna Moncrieff, a psychiatrist and researcher at University College London, elaborates:

[This study] confirms that the full degree of harm of antidepressants is not reported. They are not reported in the published literature, we know that – and it appears that they are not properly reported in clinical study reports that go to the regulators and from the basis of decisions about licensing.

This is precisely why, as I have mentioned many times in previous articles, Dr. Richard Horton, the current Editor-In-Chief of one of the most reputable peer-reviewed medical journals in the world, boldly described most published scientific literature as untrue. (source)

Marcia Angell, a physician who spent two decades as the Editor-In-Chief of The New England Journal of Medicine, puts it equally as bluntly:

It is simply no longer possible to believe much o the clinical research that is published, or to rely on the judgement of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine. (source)

Unfortunately, it’s not just antidepressants. A few years ago, Lucia Tomljenovic, a PhD in biochemistry and a senior postdoctoral fellow in UBC’s Faculty of Medicine, uncovered documents that reveal vaccine manufacturers, pharmaceutical companies, and health authorities have known about multiple dangers associated with vaccines but chose to withhold them from the public. The documents were obtained from the UK Department of Health (DH) and the Joint Committee on Vaccination and Immunization (JCVI), who advise the Secretaries of State for Health in the UK about diseases preventable through immunizations. The JCVI made “continuous efforts to withhold critical data on severe adverse reactions and contraindications to vaccinations to both parents and health practitioners in order to reach overall vaccination rates.” (source)

Now, vaccines are a completely different topic, but the point to be made here is that pharmaceutical companies withhold critical data from physicians, researchers, and the general public. They are motivated by profit, and when pitted against consumer safety, profit always wins.

“The Serotonin Theory is as Close as Any Theory in the History of Science to Having Been Proved Wrong.”

I have written about this many times before, and it’s only fitting that I do so now as well. Is the chemical imbalance theory of depression really true, or is it just a tool used to push more drugs onto the market? After all, antidepressant drugs are the most commonly prescribed drugs in North America. Pharmaceutical companies are bringing in billions of dollars every single year from the sale of antidepressant drugs alone, and they also spend billions of dollars marketing and advertising their products.

Joseph Coyle, a neuroscientist from Harvard Medical School, sums it up best, writing that “chemical imbalance is sort of last-century thinking. It’s much more complicated than that.” And it’s true; depression is much more complicated than that, at least compared to the commonly accepted belief that depression results from a chemical imbalance in the brain. This idea was posed in the late 1950s and has since taken hold in everyone’s minds. It’s the general idea that a deficiency of select neurotransmitters exists (chemical messengers) at critical points, like synapses. One of these neurotransmitters, for example, is serotonin; others include norepinephrine and dopamine.

As Scientific American reports, “much of the general public seems to have accepted the chemical imbalance hypothesis uncritically,” and that “it is very likely that depression stems from influences other than neurotransmitter abnormalities.” (source)

Harvard Medical School put out a press release a few years ago stating that it’s “often said that depression results from a chemical imbalance, but that figure of speech doesn’t capture how complex the disease is.”  (source)

Of course, there are brain events and biochemical reactions occurring when someone feels depressed, as there are all the time, but no research has ever established that a particular brain state causes, or even correlates with, depression. . . . In all cases studies yield inconsistent results, and none have been shown to be specific to depression, let alone causal. 

The fact that more than 50 years of intense research efforts have failed to identify depression in the brain may indicate that we simply lack the right technology, or it may suggest we have been barking up the wrong tree!

Dr. Joanna Moncrieff,  British Psychiatrist, Author (source)

The most commonly cited evidence to support the chemical imbalance theory is simply that some drugs have been shown to increase and decrease mood in human and animal models, and yes — many antidepressants increase the amounts of serotonin and other neurotransmitters at synapses, but what we fail to realize today is, just because mood can be artificially manipulated with drugs, does not mean the chemical imbalance theory is true. Just because these antidepressants do increase and decrease certain chemical levels in the brain does not prove the chemical imbalance theory of depression.

We simply can’t currently determine if a human being has a chemical imbalance (to whatever extent) or say what neurotransmitters are involved, which is why the chemical imbalance theory of depression remains a theory. It’s not like chemical levels in the brain can accurately be measured or ‘looked at,’ either.

Yet much of the general public still accepts the chemical imbalance theory. Indeed, a survey conducted in 2007 of 262 undergraduates at Cleveland State University found that more than 80 percent of the participants found it “likely” that chemical imbalances cause depression.

“At best, drug-induced affective disturbances can only be considered models for natural disorders, while it remains to be demonstrated that the behavioral changes produced by these drugs have any relation to naturally occurring biochemical abnormalities which might be associated with the illness.” (source)

Keep in mind, as Harvard Medical School points out, there are probably many chemicals involved, working both inside and outside of our nerve cells: “There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.”

“The cause of mental disorders such as depression remains unknown. However, the idea that neurotransmitter imbalances cause depression is vigorously promoted by pharmaceutical companies and the psychiatric profession at large.” (source)

Again, theories like the low serotonin one came into existence because scientists were able to observe the effects of drugs on the brain. It was a hypothesis that attempted to explain how drugs could be fixing something, yet whether or not depressed people actually had lower serotonin levels actually remains to be proven. You can read more about the science here.

“The serotonin theory is simply not a scientific statement. It’s a botched theory – a hypothesis that was proven incorrect.” – Dr. Joseph Mercola (source)

Not only is there no solid scientific proof to back up the chemical imbalance theory, many depressed people are not even helped by taking antidepressants like SSRIs. For example, a review done by the University of California in 2009 found that one third of people treated with antidepressants do not improve, and a significant portion of these people remain depressed. As Scientific American observes, “if antidepressants correct a chemical imbalance that underlies depression, all or most depressed people should get better after taking them.”

Depression has one focus, brain chemistry, even though it is a multifaceted issue involving many concerns and many chemicals. Focusing on this one chemical imbalance theory, and then dishing out drugs that actually alter brain chemistry, is shortsighted and dangerous.

“In spite of the enormous amount of money and time that has been spent on the quest to confirm the chemical imbalance theory, direct proof has never materialized.”  (source)

The irony of this situation is hopefully not lost on everyone. The only imbalances we know for sure to exist in the brains of ‘mentally ill’ people are the ones inflicted on them by psychiatric drugs. We are making a false claim that they have biochemical imbalances and then actually giving them biochemical imbalances based on that claim.

For some natural ways to combat depression. You can read THIS article. 


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