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The Serotonin Theory of Depression

I had originally posted this early last year, but I was inspired to repost this after reading an article on Green Drink Diaries where she shares her story of overcoming anxiety and depression. I strongly related to her journey and her blog is amazing (she talks in depth how she recovered from cancer in using alternative methods).

Many people think that exercise and nutrition have not all that much to do with their depression. That depression is not something that is in their realm to control (at least not without a bit of pharmaceutical help). I would imagine this is because of a theory out there that most medical professionals are reciting: there is a chemical imbalance in the brain that is making a person depressed. This is where I am going to start.
I would like to add - It is not my intent to be hurtful or inconsiderate to those people that are on medication and/or suffering from depression. We each have our own path and we can all learn from each other. Just the fact that someone is doing something about it makes a difference.

The following is not my opinion or wording. Please see throughout citations and review authors at the bottom of the page.
The Serotonin Theory

[1] The low serotonin theory arose because researchers understood how antidepressant drugs acted on the brain; it was a hypothesis that tried to explain how the drug might be fixing something. However, that hypothesis did not hold up to further investigation. Investigations were done to see whether or not depressed people actually had lower serotonin levels, and in 1983 the National Institute of Mental Health (NIMH) concluded that:
[8] "There is no evidence that there is anything wrong in the serotonergic system of depressed patients."
[1] The serotonin theory is simply not a scientific statement. It's a inferior theory—a hypothesis that has been proven incorrect.
[1] The fact that this theory continues to thrive is destroying the health of millions, because if you take an SSRI drug that blocks the normal reuptake of serotonin, you end up with the very physiological problem the drug is designed to treat–low serotonin levels. Which, ironically, is the state hypothesized to bring on depression in the first place.
[2] In 1996, neuroscientist Steven Hyman, who was head of the NIMH at the time, and is today Provost of Harvard University, published the paper Initiation and Adaptation: A Paradigm for Understanding Psychotropic Drugs, in which he explains this chain of events: once your brain has undergone a series of compensatory adaptations to the drug, your brain operates in a manner that is "both qualitatively and quantitatively different than normal."
[1] So, it's important to understand that these drugs are NOT normalizing agents. They're abnormalizing agents, and once you understand that, you can understand how they might provoke a manic episode, or why they might be associated with sexual dysfunction or violence and suicide, for example.

[3] Medical journalist and Pulitzer Prize nominee Robert Whitaker explains the history of the treatment of those with severe mental illness in his first book, Mad in America. His latest book, Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness in America focuses on the disturbing fact that as psychiatry has gained ground, mental illness has skyrocketed.

[3] SSRI's have been shown to increase your risk of developing bipolar depression, according to Whitaker. Anywhere from 25 to 50 percent of children who take an antidepressant for five years convert to bipolar illness. In adults, about 25 percent of long term users convert from a diagnosis of unipolar depression to bipolar. 
[1] This is a serious concern because once you're categorized as bipolar, you're often treated with a cocktail of medications including an antipsychotic medication, and long-term bipolar outcomes are grim in the United States. For starters, only about 35 percent of bipolar patients are employed, so the risk of permanent disability is great.


[4] "It is high time that it was stated clearly that the serotonin imbalance theory of depression is not supported by the scientific evidence or by expert opinion.” - Dr Joanna Moncrieff, Senior Lecturer in Psychiatry at University College London
[5,6] Researchers Jeffrey Lacasse, a doctoral candidate at Florida State University and Dr. Jonathan Leo, a neuroanatomy professor at Lake Erie College of Osteopathic Medicine -- studied US consumer advertisements for SSRIs from print, television, and the Internet. They found widespread claims that SSRIs restore the serotonin balance of the brain. "Yet there is no such thing as a scientifically established correct 'balance' of serotonin".

[5,6] According to Lacasse and Leo, in the scientific literature it is openly admitted that the serotonin hypothesis remains unconfirmed and that there is "a growing body of medical literature casting doubt on the serotonin hypothesis," which is not reflected in the consumer ads.

[7] Archives of General Psychiatry found evidence of increased serotonin activity in depressed persons. Furthermore, growing evidence suggests that it is an error to even talk about the brain having a single serotonin level.  Based on work with rats and mice, neuroscientists are increasingly moving to the view that there are different populations of serotonin neurons that are each independently regulated.
Exercise as a better antidepressant?
[9, 10] James A. Blumenthal, Ph.D. and his colleagues surprised many people in 1999 when they demonstrated that regular exercise is as effective as antidepressant medications for patients with major depression.  According to Blumenthal "Our findings suggest that a modest exercise program is an effective, robust treatment for patients with major depression who are positively inclined to participate in it.  The benefits of exercise are likely to endure particularly among those who adopt it as a regular, ongoing life activity."

[9,10] A very interesting finding concerns the group that received both Zoloft and exercise.  The subjects on Zoloft were more likely to again become depressed than the subjects who only exercised. 
[11] Michael Otto, a College of Arts & Sciences professor of psychology, says clinicians should consider physical activity as important and valid a treatment for depression. Otto argues that numerous clinical trials have shown that people with major depression who embrace routine exercise get better at the same rate as they do with antidepressants.
[11] A significant percentage of them could improve dramatically with exercise alone, and for patients who still require medication, it can increase the benefit, says Otto, one of a group of researchers calling for psychologists to include exercise programs in treating not just depressives, but people with anxiety and eating disorders.

What About the Placebo Effect…

[12] The debate about treating depression with drugs, psychotherapy, or a combination of both drugs and psychotherapy has raged on over the years. But a recent analysis of 39 studies of 3,252 depressed patients, presented at the American Psychological Association's (APA) 104th annual convention, found that 50 percent of the drug effect is due to the placebo response.

[13] The effectiveness of antidepressants is mainly in the placebo effect of treatment, not in the medication itself, according to Irving Kirsch.
[13] Seventy-five percent of the response to medication for depression was a result of the patient being in treatment, while at the most 25 percent of the response was a true drug effect, asserts Kirsch (a professor of psychology, and former UConn graduate student Guy Sapirstein)
[13] "This means that for a typical patient, 75 percent of the benefit obtained from the active drug would also have been obtained from an inactive placebo," -Kirsch "Whether the remaining 25 percent of the drug response is a true effect of the drug or a psychologically triggered response to side effects alone cannot yet be determined."

References Cited:

[1] Dr. Joseph Mercola, University of Illinois, Chicago College of Osteopathic Medicine, Board Certified American College of Osteopathic General Practitioners, State of Illinois Licensed Physician and Surgeon

[2] Steven Hyman, neuroscientist, Provost of Harvard University. Initiation and Adaptation: A Paradigm for Understanding Psychotropic Drugs
[3] Robert Whitaker, Medical journalist and Pulitzer Prize nominee. Mad in America. , Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs and the Astonishing Rise of Mental Illness in America.
[4] Dr. Joanna Moncrieff, Senior Lecturer in Psychiatry at University College London.

[5] Jeffrey Lacasse, a doctoral candidate at Florida State University
[6] Dr. Jonathan Leo, a neuroanatomy professor at Lake Erie College of Osteopathic Medicine. Consumer Advertisements for Psychostimulants in the United States. February 26, 2009
[7] Jonathan Rottenberg, Ph.D. The serotonin theory of depression is collapsing. Published on July 23, 2010
[8] National Institute of Mental Health, 1983

[9] James A. Blumenthal, Michael A. Babyak, Kathleen A. Moore, W. Edward Craighead, Steve Herman, Parinda Khatri, Robert Waugh, Melissa A. Napolitano, Leslie M. Forman, Mark Appelbaum, P., Murali Doraiswamy, K., Ranga Krishnan. Effects of Exercise Training on Older Patients With Major Depression. Archives of Internal Medicine, October 25, 1999

[10] Michael Babyak, James A. Blumenthal, Steve Herman, Parinda Khatri, Murali Doraiswamy, Kathleen Moore, W. Edward Craighead, Teri T. Baldewicz, and K. Ranga Krishnan. Exercise Treatment for Major Depression: Maintenance of Therapeutic Benefit at 10 Months. Psychosomatic Medicine, September/October 2000.

[11] Michael Otto, coauthor, with Jasper A. J. Smits of Southern Methodist University, of the clinical guide Exercise for Mood and Anxiety Disorders (Oxford University Press)

[12] 1996 Press Release, American Psychological Association

[13] Irving Kirsch. Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication, was published in the electronic journal Prevention & Treatment,, a publication of the American Psychological Association.

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