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Antidepressants, Placebos, and the
Chemical Imbalance Theory of Depression
by Matt Moody, Ph.D. 

Understanding why the "Chemical Imbalance Theory of Depression" is a Myth requires an in-depth explanation. This article eventually addresses the Myth head on. The following foundational facts lend empirical support to the conclusion that People do not experience Depression because of Chemical Imbalance in the Brain.

By presenting this rebuttal, I am swimming upstream against the stiff current of public perception: Most people believe that depression is caused by Chemical Imbalance, and thus depression will be cured by taking Antidepressants. Why do most people believe this? Because that's likely what their Doctor told them, and that's also what a 600-billion-dollar pharmaceutical industry wants them to keep believing -- and spends many millions to advertise that errant message.

When a disease has a real biological cause, then medications with active ingredients will make a striking difference in the rates of recovery and prevention. For example in 1988 there were 350,000 cases of polio reported in 125 countries; in contrast, after the polio vaccine was discovered and vaccinations programs were implemented world-wide, only 2,000 cases of polio were reported in 17 countries in 2006.

When a disease has a real biological cause, then medications with active ingredients will make a dramatic difference in rates of recovery. Thus, if Depression really were a "Disease" caused by Chemical Imbalance, then we should expect that medications formulated to correct that chemical imbalance will cure the disease; and further, there should be a substantial difference between the effectiveness of Antidepressants compared to placebos -- Dummy Pills that patients think are Antidepressants.

Driven to Depression by unrealistic expectations about Perfection
 BURNING QUESTION: What are the results of double-blind clinical trials that compare recovery rates between Depressed Patients given Antidepressants, compared to Depressed Patients given Placebos?

Good Science Can Verify Facts through
Systematic Experiments that Control Conditions

How do we Know that anything IS, as we describe it to be? How do we Know when something is Real and Actual? How do we know that certain word-descriptions accurately correspond to REALITY?

If you carefully read the previous sentences, you will realize there are Two Levels involved in establishing REALITY. Let's re-read the previous sentences:

How do we Know that anything IS, as we describe it to be? How do we Know when something is Real and Actual; how do we know that certain word-descriptions accurately correspond to REALITY.

Truth is, we cannot escape the fact that WORDS are inseparably tied to ASSERTING claims about REALITY. How so? In order to speak of a Reality in the first place, we must NAME IT -- this way we have a word-label (or a phrase-label) to Represent the Reality being scrutinized and talked about. So there are Two Levels involved in establishing that something is Real:

1) The Consistent REALITY itself, and
2) The Accurate Description of that REALITY via Words.

The correctness of Word-Assertions is called . . . Propositional Truth. It is the goal of science to empirically prove "propositions" to be either true or false, based upon empirical observations and confirmations. Within scientific methods, propositions are called "hypotheses."

When Science is done well, scientists have no vested interest in either proving or disproving a hypothesis; instead, objective scientists are committed to having REALITY speak as it will. And competent scientists design methods that allow REALITY TO SPEAK through data that is systematically collected.

In the 1950s, a Double-blind Clinical Trial was conducted where children were given either:
1) a real polio vaccine , or
2) a placebo injection.

Double Blind means that neither the Doctors giving vaccinations, nor the patients receiving vaccinations actually know whether drugs or placebos are being administered.

In the case of this Double Blind Study that tested the efficacy of a Polio Vaccine, a dramatic difference was documented between subjects given a placebo versus subjects given a real polio vaccine. By virtue of this placebo-controlled study, Doctors and patients are now confident that Polio Vaccinations actually work.

What Double Blind Studies show when Depressed Patients
are given Placebos as compared to Antidepressants

In 2010 a study published in JAMA (the Journal of the American Medical Association) concluded:

"there is little evidence that [antidepressant medications] have a specific pharmacological effect relative to pill placebo for patients with less severe depression. ... The magnitude of benefit of antidepressant medication compared with placebo ... may be minimal or nonexistent, on average, in patients with mild or moderate symptoms."

This study was a meta-analysis of 6 other studies that compared placebos and antidepressant drugs administered to 718 patients in a double-blind context. Those conducting the Study included three Medical Doctors and three Ph.D.'s as follows: Jay C. Fournier, MA; Robert J. DeRubeis, PhD; Steven D. Hollon, PhD; Sona Dimidjian, PhD; Jay D. Amsterdam, MD; Richard C. Shelton, MD; Jan Fawcett, MD

"Placebo" is a Latin word which means "I shall please." The "Placebo Effect" is that beneficial result that occurs due to a person's belief that a treatment will be helpful, when in fact the placebo-treatment can't actually produce real beneficial effects, apart from a person's belief that the "treatment" (the placebo) will work. Clearly patients must be unaware that "nothing" is the treatment they are getting.

Placebo-controlled clinical trials create a context where Depressed Patients THINK they are being treated, and they ARE being treated but not as they suppose. Instead of getting an active-ingredient drug, they are just getting a Suggestion that a dummy pill will cure their Depression.

To measure the Placebo Effect, scientists must measure the differences in recovery rate between depressed patients who are given an Antidepressant with active ingredients . . . versus depressed patients who are given absolutely nothing (a Placebo Pill) but THINK they are getting something. Again, subjects are unaware that the Pill they are taking IS a Placebo. Studies show that the power of suggestion, or "Placebo Effect," is potent.

In 1950 Cornell researcher, Stewart Wolf, gave an active ingredient drug called Ipecac to a severely nauseated pregnant woman who had be continuously vomiting for two days. Of course, Ipecac is a drug that induces nausea and vomiting. So Wolf gave the Ipecac drug to a severely nauseated woman with the suggestion that the drug would cause her vomiting to cease. Wolf reported that within 20 minutes of ingesting the Ipecac, the pregnant woman's nausea ceased.

Stewart Wolf duplicated these results with another subject who was also having reoccurring nausea. Wolf gave this patient Ipecac syrup, but when the patient's nausea returned one hour later, Wolf then administered a second dose of Ipecac, setting the expectation that a double dose will surely cause the nausea to cease. And after this second "treatment" of Ipecac, the subject did not experience nausea through the rest of the day.

So the power of doctor suggestion and patient expectation actually reversed the effects of the Ipecac -- a drug designed to induce vomiting. Amazingly, the opposite effect was realized: nausea and vomiting ceased.

It's wise to be cautious when drawing conclusions from a sample size of One or Two subjects. All sorts of loose correlations to Positive Results can cause people to "believe" in the curing properties of a wide-range of substances that were ingested (or applied) on the days or weeks that positive results appeared. Thus, testimonials are regularly given based upon a sample size of One -- where no controls can measure the Placebo Effect, nor the real occurrence of natural, spontaneous healing.

So what did human being do, when they were depressed from the early family of Adam to the time of his descendants living up to the 1950s A.D. -- before anti-depressants were invented? Truth is, an infinitely wise Creator designed the human body and mind to spontaneously heal. But unfortunately, because some people happened to be eating Carrots or Cadbury Eggs during their time of spontaneous healing, they will sometime erroneously attribute their healing to their temporary Cuisine, instead of the Creator.

A sample size of One or Two can create False Impressions that certain substances CAUSE desirable results, when really the results are most likely due to the Placebo Effect -- positive results happening because people "believe" and "hope" that good things will happen by eating Carrots or Cadbury Eggs.

For this reason Double Blind Experiments are crucial to empirically proving what really Causes . . . what! Well-designed Double-Blind Studies will control for both the Placebo Effect and for Spontaneous Healing that occurs among subjects that receive "no treatment at all" -- not even a dummy pill.

One of the more intriguing studies about "no treatment at all" was conducted by Brigham Young University Professor of Psychology, Paul Bergin, who tracked the recovery rates between depressed patients given psychotherapy, compared to depressed persons who simply talked to a friend through their time of depression. Can you guess what Dr. Bergin dicovered? Truth is, talking to a friend is NOT simply "no treatment at all," rather it is an interaction that allows a depressed person to both vent frustrations as well as be heard and understood. And speaking of the effectiveness of psychotherapy:

What Double Blind Experiments show when Depressed Patients
are given Psychotherapy Only . . . compared to Antidepressants

Irving Kirsch, Ph.D. did a meta-analysis of 38 clinical trials that included 3,000 depressed persons, divided into four groups:

1) Patients given an active ingredient drug -- an antidepressant
2) Patients treated with psychotherapy
3) Patients given a placebo pill
4) Patients given no drugs, placebos, or psychotherapy -- no treatment.

Kirsch found that the recovery rates for the Drug Group compared to the Psychotherapy Group were the same; further, that Drug Treatment and Psychotherapy Treatment were substantially more effective for reducing and relieving the symptoms of depression, compared to "no treatment at all."

First, if Depression is actually caused by Chemical Imbalance within the Brain, then why do Depressed Patients receiving Psychotherapy (and no drugs) recover at the same rate as Depressed Patients given an antidepressant drug? How can Talking to a depressed person possibly bring Serotonin levels into balance?

Second, if Depression is actually caused by Chemical Imbalance within the Brain, then why do Depressed Patients receiving a Placebo (Dummy Pill) recover at a rate substantially greater than "no treatment at all" -- a rate that is not significantly lower compared to the Drug Group?

Here's what the researcher, Irving Kirsch, said of the research findings:

"Sapirstein and I were not surprised to find that there was a powerful placebo effect in the treatment of depression. ... What did surprise us, however, was how small the difference was between the response to the drug and the response to the placebo."

To study the effect of Placebos (dummy pills) given to Depressed Patients, solid scientific methods must do more than merely compare effects between Patients given antidepressant drugs . . . versus Patients given placebos -- solid science will also compare the recovery rates of depressed persons who receive "no treatment at all," not even dummy pills. By taking account of the "no treatment at all" group, the "placebo effect" can be measured. In the Kirsch & Sapirstein Study, the Placebo Group showed recovery rates substantially greater than the no-treatment group -- the difference was 3x greater when Patients were "treated" with Placebos.

In the Polio Vaccine Study previously mentioned, millions of people received either a real polio injection or a placebo injection; in the end, the Drug out performed the Placebo significantly.

When an illness has real biological causes, we should expect that real medicine will be more effective than either Talk-Therapy or a Placebo-coupled-with-Hope. The Polio Vaccine is known to be effective by virtue of empirical evidence. Again, in 1988 there were 350,000 cases of polio reported in 125 countries; then after polio vaccination programs were instituted, only 2,000 cases of polio were reported in 17 countries in 2006

If Depression were actually caused by Chemical Imbalance within the Brain, then why do Depressed Patients receiving Psychotherapy (and no drugs) recover at the same rate as Depressed Patients given an antidepressant? Further, why is the difference so small between Depressed Patients given a real Antidepressant Drug versus those given a Placebo?

Taking antidepressant drugs yields the SAME RESULT compared to talking with a therapist. If the "chemical imbalance theory of depression" were Real, then this simply would not be the case; any more than one would expect to find Polio Patients recovering from Polio as a result of talking to a Therapist. In the case of Polio, the disease has a real biological Cause. But in the case of Depression, abundant scientific evidence has disproven the "Chemical Imbalance Theory of Depression."

A Direct Test of the Chemical Imbalance Theory of Depression:
Comparing Recovery Rates between Antidepressants that Increase Serotonin
versus Antidepressants that Decrease Serotonin

The Chemical Imbalance Theory of Depression assumes that a depressed person has insufficient Serotonin in the brain; thus giving a Depressed Patient more Serotonin should relieve the symptoms of Depression. Here's a little history of how that "Chemical Imbalance" assumption came to be.

In 1965, Joseph Schildkraut published a ground-breaking paper asserting that depression was caused by a deficiency of a certain neurotransmitters in the brain. In 1967 a physician named Alec Coppen published a paper asserting the Chemical Imbalance Theory of Depression, wherein he emphasized "serotonin" to be the neurotransmitter that was lacking in the brain.

But if Alec Coppen's theory were correct, then Depression could be induced in normal, happy people simply by giving them a drug that decreases Serotonin levels. So here's two BURNING QUESTIONS:
Is that what empirical studies have shown: that people will become depressed when Serotonin levels are intentionally lowered? And, has double-blind experimentation shown that Depression can be induced by lowing Serotonin levels in normal people?

Antidepressants like Prozac and Zoloft increase serotonin levels. From Boston.com, here's a description of Prozac and the Chemical Imbalance Theory of Depression:

"PROZAC IS ONE of the most successful drugs of all time. Since its introduction as an antidepressant more than 20 years ago, Prozac has been prescribed to more than 54 million people around the world, and prevented untold amounts of suffering. But the success of Prozac hasn't simply transformed the treatment of depression: it has also transformed the science of depression.

"For decades, researchers struggled to identify the underlying cause of depression, ... But then came Prozac. Like many other antidepressants, Prozac increases the brain's supply of serotonin, a neurotransmitter. The drug's effectiveness inspired an elegant theory, known as the chemical hypothesis: Sadness is simply a lack of chemical happiness. The little blue pills cheer us up because they give the brain what it has been missing."

But from the very same online article comes this BUBBLE BURSTER: "There's only one problem with this theory of depression: it's almost certainly wrong." Here's why the Chemical Imbalance Theory . . . doesn't fly!

Dozens of studies have been conducted to observe what happens when Serotonin levels are intentionally reduced. Again, IF the Chemical Imbalance Theory of Depression is correct, then decreasing Serotonin levels in healthy adults should cause Depression. But in a meta-analysis of at least 90 Depression Studies, researchers at the University of Amsterdam (H.G. Ruhe, N.S. Mason, and Aart H. Schene, 2007) found no evidence that lowering serotonin levels induces depression.

That Chemical Imbalance in the Brain causes Depression is the default assumption among many within the medical community, and thus broadly-accepted within society. And because the Chemical Imbalance Theory is so pervasive, the words, "you have a chemical imbalance in your brain" have become a diagnostic cliche for numerous medical doctors.

Recently I spoke with someone who told me of his last visited to the Doctor: After a brief 5 minute verbal interview the Doctor announced, "you have a chemical imbalance in your brain," and then proceeded to write out a prescription for an Antidepressant to cure the alleged imbalance.

And what's wrong with this picture?

The Doctor didn't do any biological tests to determine an actual Chemical Imbalance; instead, the Doctor simply invoked the Chemical Imbalance Theory -- the same Theory that has been disproven by dozens of double-blind clinical trials, over many decades of testing.

Double-blind studies undercut the credibility of the Chemical Imbalance Theory of Depression on these points:

1)  Psychotherapy is as effective for relieving depression as Antidepressants; suggesting that Depression
      is not really caused by bad biology -- Depression is not really caused by chemical imbalance.

2)  Antidepressants are not significantly more effective than placebos for relieving depression; also 
      indicating that Depression initiates psychologically (or spiritually) and not biologically.
3)  Antidepressants that decrease Serotonin levels have been shown to relieve Depression, instead of cause it -- 
      a finding that directly contradicts the central premise of the Chemical Imbalance Theory of Depression.

This last point deserves emphasis, because it so clearly and directly contradicts the premise of the Chemical Imbalance Theory of Depression.

FIRST, it is a fact that two of the most prominently prescribed antidepressants are Prozac and Zoloft, and they contain active ingredients that increase Serotonin levels. And according to the Chemical Imbalance Theory of Depression, when you supply a greater amount of Serotonin to the Brain, then a Depressed Person's Chemical Imbalance is cured. BUT if the Imbalance Theory were correct, then taking Antidepressants that decrease Serotonin Levels should make a person's Depression worse -- empirical findings show the exact opposite:

FACT: Antidepressants that decrease Serotonin levels have been proven to relieve Depression, just as well as Antidepressant that increase Serotonin levels, like Prozac and Zoloft. Now add to this, the fact that Placebos (dummy pills with no active ingredients) amazingly, work just as well as real pills -- as long as depressed patients believe they are taking real Antidepressants.

Finally, the beauty of the Placebo is this: there are NO SIDE EFFECTS like those listed in the small print of every Antidepressant's product information, for example:

  • Dry mouth
  • Urinary retention
  • Blurred vision
  • Constipation
  • Sedation (interfering with operating machinery and driving).
  • Sleep disruption, Insomnia
  • Weight gain
  • Headache
  • Nausea
  • Gastrointestinal disturbance
  • Diarrhea.
  • Abdominal pain.
  • Inability to achieve an erection.
  • Inability to achieve orgasm
  • Loss of libido.
  • Agitation.

The catch with taking Placebos is this: Depressed Patients must believe that Placebos provide a real cure; and they must NOT know that "nothing-but-hope" is the treatment they are getting. In the end, a spiritually-based HOPE and BELIEF work very well for relieving Depression.

So people who believe they will recover from depression ... do recover, even when they unwittingly ingest a placebo pill. They get better at essentially the same rate as those given Antidepressants with active ingredients. And why is this so?

Just as God created a human body that will spontaneously heal itself when skin is torn or bones are broken, our all-wise and loving Creator has also showered humanity with Healing Hope through the Atonement of His Son -- thus a person's spiritually-based "belief"and"hope" that things will get better ... are directly empowered by the Savior, Jesus Christ -- the True Vine, with Whom we must abide, else "ye can do nothing" (John 15:5).

To be clear, when I speak of Placebo Pills working as well as Anti-depressants with active ingredients, I'm NOT suggesting that Positive Mental Attitude is the primary power by which people get better; rather, I'm saying that our healing is based in a Gift which God is freely willing to give, if we will but remove the attitude of HOPE-less-ness from our Heart and Minds. And that removal is assisted by the "Placebo Effect" -- for after all, we are taking medications that will heal, right?

The very definition of depression is fundamentally about giving up HOPE. So when a person takes a medication (that is really a placebo), then the person is no longer beset with HOPE-less-ness. In the end, Positive Mental Attitude is NOT the primary power that brings forth wonderful things. Instead, the Atonement of Jesus Christ is the primary power by which all good things exist. And Positive Mental Attitude is one of those good things; it is a fruit of the Spirit, along with "love, joy, peace, patience, gentleness, goodness, faith" (Galatians 5:22).

Matt Moody, Ph.D.
Social Psychologist

P.S. It is impossible to feel cold when standing in the full brightness of the Sun. Here's two Bible verses that suggest that a person will not feel Depressed when walking in the Spirit, and feeling the Savior's healing hand:
            "Come unto me, all ye that labour and are heavy laden, and I will give you rest." (Matt. 11:28).
            "But the fruit of the Spirit is love, joy, peace"
(Gal. 5:22).

Related Articles:
Do I Really Have a Choice NOT to Be Stressed Out?

Why You Cannot Directly Think Yourself into Being Happy
As A Man Thinks So Is He: Clarifying A Commonly Misinterpreted Proverb
The Secret of Life is Everyone's Possession: Principles of Emotional Healing and Lasting Change

* * * * * * *

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