Mark Gundersen

Psych 493C

Contemporary Controversies in Clinical Psychology and Psychopathology

Started out as curiosity about how neurons communicated in the brain

1936:Henry Dale, along with Otto Loewi, won the

Nobel Prize in Physiology or Medicine for demonstrating neurohumoral transmission

Alluded to the existence of the brain neurotransmitters when he mentioned that acetylcholine was found in the brain along with other neural synapses throughout the body (1)

1960 Serotonin and GABA (γ-aminobutyric acid) found in animal

brains John Gaddum studied the effect of LSD, which was seen to

block the effects of serotonin on the function of smooth muscles in the gut

Applied findings with brain serotonin – LSD causes hallucination in the subject, could it be inhibiting serotonin function in the brain?

John Gaddum concluded that serotonin may be the chemical that “keeps us sane” (1)

1963 Feldberg wrote the book “A Pharmacological Approach to

the Brain”(1) Listed 50+ behavioral and physiological responses to various drugs

injected into the brain Physostigmine – affect acetylcholine transmission

Change in Blood Pressure, Pupillary size, Salivation, Respiration Chloralose (anesthetic)

Increase in Playfulness, Rage, Fear, Excessive Eating

1965Most opposition to chemical transmission in

the brain had changed their viewpoint to accept the new theory as a valid hypothesis

The head of the anti-chemical movement, John Eccles, abandoned his stance of promoting only electrical synapses controlling transmission (1)

The “War of the Soups and Sparks” ended, and the viewpoint of chemical synapses being primarily responsible for brain neurotransmission was widely accepted (2)

What is it? It is defined as the theory that there is a neurotransmitter imbalance between

synapses of the brain, resulting in psychiatric disorders (3) The most common of these theories is the concept that depressed patients

have a lower-than-normal level of serotonin between synapses in the brain, causing from mild to acute forms of depression (3)

A press release on Lexapro states “While the brain chemistry of depression is not fully understood, research

suggests that depression is caused by an imbalance of certain chemicals in the brain, most notably serotonin.”

Another press release on the drug Luvox states “Both depression and OCD are thought to be caused by the imbalance of a

chemical in the brain called serotonin, which sends impulses from one nerve to another.”

A release on Paxil states “Scientific evidence suggests that depression and certain anxiety disorders

may be caused by a chemical imbalance in the brain.” Another release explaining the effect of Prozac states

“Depression is not fully understood, but a growing amount of evidence supports the view that people with depression have an imbalance of the brain’s neurotransmitters…Many scientists believe that an imbalance of serotonin may be an important factor in the development and severity of depression.” (4)

A press release on Lexapro states “While the brain chemistry of depression is not fully

understood, research suggests that depression is caused by an imbalance of certain chemicals in the brain, most notably serotonin.”

Another press release on the drug Luvox states “Both depression and OCD are thought to be caused by the

imbalance of a chemical in the brain called serotonin, which sends impulses from one nerve to another.”

A release on Paxil states “Scientific evidence suggests that depression and certain

anxiety disorders may be caused by a chemical imbalance in the brain.”

Another release explaining the effect of Prozac states “Depression is not fully understood, but a growing amount

of evidence supports the view that people with depression have an imbalance of the brain’s neurotransmitters…Many scientists believe that an imbalance of serotonin may be an important factor in the development and severity of depression.”

Depression and Anxiety1960’s

The drug reserpine was issued to animals, which resulted in them becoming inactive and unresponsive. This led scientists to believe that reserpine may cause

depressive episodes Further neuropharmacological research established that

reserpine depressed the function of certain monoanimes (serotonin and norepinephrine) in the brains of animals.

By assumption, scientists attributed that depressive episodes in humans was caused by a depletion of either serotonin, norepinephrine, or a combination of both.What scientists overlooked was the fact that reserpine

did not cause a depressive episode in most humans (94%) as it looked like it did in animals.

Moreover, further examination of these results yielded that fact that the 6% of people that exhibited depression after reserpine tests had all had previous episodes of depression. (2)

Depression and Anxiety Cont.1996

A more recent study was conducted at Yale University by Heninger, Delgado, and CharneyThey studied the effects of monoamine (serotonin) depletion

on depressive symptoms in depressed and recovered patients off medication, as well as in healthy controls.

They results contradicted popular belief: Serotonin depletion did NOT increase depressive symptoms in

clinically ill patients off treatment Serotonin depletion did NOT produce depressive symptoms in normal

controls Patients who had recovered from a prior history of depression did

relapse following serotonin depletion (5)These findings should have forced a major revision in the

monoamine theories of depression, but still today we see that clinicians prefer to blame serotonin for most depressive symptoms.

Depression and Anxiety Cont. 1998

Kirsch and Saperstein conducted a meta-analysis of 20 different studies that compared anti-depressant medication to placebo, representing data on 2,328 patients. Based on the analysis, they concluded that 75% of the effect of the certain anti-

depressant medication can be accounted for by the placebo effect (6) 2002

Kirsch, Moore, Scoboria, and Nicholls re-analyzed data reported from the FDA (Food and Drug Administration) for the approval of six widely prescribed anti-depressant medications The medications included: Prozac, Paxil, Zoloft, Effexor, Serzone, and Celexa

There were 47 randomized placebo controlled studies for the six drugs, where individuals were randomly placed in either the anti-depressant category or the placebo category. Also, the studies were double-blind, meaning that neither the participant nor the prescriber new what group the patient was placed in

The conclusions were that 82% of the results could be accounted for by the placebo effect and 18% was due to the agent in the medication Moore went back and included 40 more studies that were previously unreleased

by the FDA because they failed to show significant drug effect, and he found that 11% of the results could be accounted for by the pill in question, an insignificant result for the effects of the drugs used. (6)

Correlation does not equal Causation Bruce Lachter, a successful psychiatrist, states in an article in “Australasian

Psychiatry” that depressed patients do not suffer from a chemical imbalance There may, in fact, be a chemical imbalance (which says nothing at all about

the direction of causation) but the suffering of a depressed individual stems from loss, fear, hostility, or trauma

It seems more and more that psychiatrists are correlating a subjective exhaustion (environmental) with an objective exhaustion (depletion of certain brain molecules). The latter explanation rectifies the hypothesis of a chemical imbalance in the brain being the cause. (7)

The Diabetes Metaphor A common metaphor used by clinicians in describing depressed patients is

“Just like diabetics need to take insulin, people who have depression need to take medication.”

Depression, however, is more accurately described as a type of mood with biological, cognitive, and behavioral manifestations.

This does not qualify depression as a type of disease as the “diabetes metaphor” tries to explain it to be

Diabetes has been proven to be caused in some cases by lack of exercise and poor diet, choices that the individual makes concerning his/her environment

Depression and anxiety, on the other hand, have no evidence of either causing a chemical imbalance in humans or vice versa. A simple correlation is all that has been proven to exist (6)

Dr. Peter Breggin Internationally known psychiatrist and author

Dr. David Cohen Professor at the School of Social Work at Miami Florida

International University Recognized as an expert on the adverse effects of psychotropic

drugs and on psychotropic drug withdrawl In their book “Your Drug May Be Your Problem”, they state that

“As confirmed in animal research, all psychiatric drugs directly affect the brain’s normal chemistry by disrupting it”

All four main SSRI’s (selective serotonin reuptake inhibitor) block the removal of the neurotransmitter from the synaptic cleft

This overabundance of serotonin causes the system to become highly hyperactive

However, it has been seen in animal tests that the brain counter-acts the over-activity by simply limiting the reaction it has toward serotonin, otherwise known as “downregulation”

The brain also inhibits it’s output of serotonin to combat the sudden overabundance

Some receptors actually disappear or die off completely, possibly becoming a permanent change (8)

Joseph Glenmullen, M.D. Clinical Instructor in Psychiatry at Harvard Medical School On staff at Harvard University Health Services In private practice in Harvard Square

Wrote the book “Prozac Backlash” Describes the inherent dangers of future chemical

imbalances that common anti-depressant/anti-anxiety drugs cause

Most SSRI’s successfully block most reuptake of serotonin by the presynaptic neuron, which from current research, has shown to involve changes in the actual DNA of the cells in response to the excess serotonin

Changes in such DNA are permanent in some instances, even after the drug has been removed, and can lead to long-term effects on brain functioning “When discussing brain cell damage caused by street drugs such as

amphetamines, cocaine, or ecstasy, researches speak in the gravest terms, warning of dread effects. Only when referring to prescription drugs do they suggest that pruning nerve cells may be ‘therapeutic’.” (9)

Joanna MoncrieffRespected academic and practicing psychiatristWrote “The Myth of the Chemical Cure”

Questions the fact that psychoactive drugs are being used under the “disease-centered model of drug action”

She contends this belief by stating that psychoactive drugs do not have any disease specific action at all, they “exert similar effects on anyone who takes them by acting on the nervous system to produce a state of altered consciousness” (10)In short, psychoactive drugs create a new chemical

imbalance that alters normal behavior of the brain, much like alcohol may inhibit our motor functions

Dr. Breggin and Dr. Cohen bring to light the procedures done to actually study the hypothesis of there being a chemical imbalance in the brain:Most tests are done on normal brains of animals

Usually attempted with healthy ratsThe techniques used, however, cannot sufficiently

test the actual amount of substances within the synapses between cells (8)Is it all just guess work?

Not entirely, what we are studying is, in fact, the change in brain chemistry after certain drugs are introduced, which brings us back to the debate of what caused what, the depressive symptoms causing the chemical imbalance, or the drugs causing a chemical imbalance that is then correlated with the symptoms

How can we actually test human brains?Due to ethical and legal constraints, scientists

cannot proceed with experiments on the human brain that may impair or damage the brain itselfSuch tests that are completed on animals are

implanting electrodes or injecting minute quantities of a drug to certain areas of the brain and studying the result

So when drug advocates praise a psychiatric drug such as Lithium or Prozac for reversing the causes of depression in humans, they are merely basing their confidence on animal research and speculation (8)

Once we can properly examine and understand the neural workings of the brain and study each synapse, then scientists can stop making scientific assumptions

On June 27th, 2005, the president of the American Psychiatric Association (APA), Steven Sharfstein, admitted to viewers everywhere that there is no way to test for a “chemical imbalance” as the cause for mental disorders

Elliot Valenstein, Ph. D. stated, “There are no tests available for assessing the chemical status of a living person’s brain” in 2005

In 2004, psychiatrist M. Douglas Mar debunked the theory that brain scans can help diagnose mental diseases, stating, “There is no scientific basis for these claims of using brain scans for psychiatric diagnoses” (11)

Kelly O’Meara, an award winning investigative reporter charges people to “ask their physician for a paper copy of the results of the test that was

conducted to measure you brain chemical levels…and one might assume that a similar test will be done at the end of the treatment”

“It is fair to say that if objective, confirmable proof of a neurological ‘chemical imbalance’ were required prior to filling a prescription for any of the psychiatric mind-altering antidepressants that reportedly ‘correct’ the imbalance in the brain, not a single prescription would be written because to date the only known method of determining chemical levels in the brain is during autopsy” (12)

Again, the top leaders in the field of psychiatry are starting to abandon their posts as promoters for the theory of chemical imbalances If this is the case, then why are psychoactive drugs still being administered

to the public in mass quantities?

One proponent theory to the continuing production and selling of psychoactive drugs to the public is the push and campaigning of drug companies It is estimated that more than thirty million people worldwide

have take Prozac, and millions more have taken one of the other SSRI’s to battle depression and anxiety (2)

Marcia Angella, an editor for twenty years of the “New England Journal of Medicine” has followed the practices of drug companies She states that the most profitable industry in the united States is

the pharmaceutical industry, taking in more than 200 billion dollars a year

The net return of all other industries in 2001 was about 3%, whereas the net return of drug companies was closer to 18%

The combined profits of the ten drug companies listed in the Fortune 500 was more than the summation of all the profits of the other 490 companies

In 2000, the pharmaceutical industry spent 14% of sales on research and 31% of sales on advertising That is almost 2.5 times was is spent on research and development! (6)

In regards to the concern that pharmaceutical companies gaining so much power over the financial market of the US, in 2004 congressional hearings were held pertaining to the number of scientists at NIH that were on retainer and had other financial connections to drug companiesCongress had found over 100 cases where

scientist had reported no outside income (as required by NIH regulations)Payments included the availability of stock options in

the company in questionIn one case, Pfizer had paid one researcher more

than a half a million dollars

The Federal Drug Administration (FDA) Requires that advertisements cannot be false or misleading and

must present information that is not inconsistent with the product label

Any companies that divulge from these guidelines can receive warnings and possibly be sanctioned

An advertisement may be cited as false or misleading if “it contains claims concerning the mechanism or site of drug action that are not generally regarded as established by scientific evidence without disclosing that the claims are not established and the limitations of the supporting evidence” Thus, stating that serotonin MAY be the cause of clinical depression is allowed

only if the limitations of the supporting evidence is provided in the advertisement (13)

As was showed in the press releases of common SSRI’s as well as the Zoloft ad, this guideline is not followed at all

The FDA also charges industries to not have advertisements that include content that “contains favorable information or opinions about a drug previously regarded as valid but which have been rendered invalid by contrary and more credible information”

With this in mind, practically all SSRI advertisements continue to use the concept of an imbalance of serotonin, when in fact there has yet to be a determined normal level of serotonin in the brain (13)

Seroxat was an SSRI developed by GlaxoSmithKine in the United Kingdom It was stated to replace serotonin in the brain to

help with the chemical imbalance that causes depression and anxiety

When patients were placed on the drug, their symptoms alleviated and the drug was praised as a success

However, as patients began to be taken off of the drug, their symptoms returned, most likely due to the masking of the actual mental condition by SerotaxWithdrawl symptoms sky rocketed, and patients began

to continue to purchase the drug in hopes of masking their depression yet again (14)

GlaxoSmithKline was taken under investigation by the MHRA (Medicine and Healthcare products Regulatory Agency, ending in 2008 Between April 1994 and September 2002, GSK conducted 9 studies of

the effect of Serotax in the treatment of pediatric depression and anxiety

At the time Serotax had the following disclaimer in relation to its use with children: “Children: The use of Seroxat in children is not recommended as safety and

efficacy have not been established in this population”. It was known that serious side effects, including suicidal tendencies, had been

observed in some adults who were in separate trials of the medication The first two of these studies were concluded in 1998 and resulted in

finding no significant changes in children given Serotax in regards to their depressive symptoms

Seven more studies were conducted and finished in 2002, none of these trials demonstrated the efficacy of Serotax either

Despite the fact that no efficacy of Serotax was found in any of these trial, and the possible danger of placing children under this medication, 32,000 children were prescribed the drug

The eventual ruling of the MHRA was not guilty in regards to the charges brought against GSK because at the time of the trials, there was no required notifications of adverse effects (15)

In regards to the debate on whether or not chemical imbalances in the brain exist, there is much more research that must be done before a scientific conclusion can be reached

No study has yet to empirically prove that chemical imbalances cause psychiatric disorders or vice versa

It is irresponsible for respectable scientists and researchers to jump on the chemical bandwagon before proper studies have been completed

The possible effect of drug companies on the research conducted on the drugs that they produce is a concern that needs to be addressed

1) Valenstein, E. (2007). The War of the Soups and the Sparks: The Discovery of Neurotransmitters and the Dispute Over How Nerves Communicate. New York: Columbia University Press.

2) Valenstein, E. (1998). Blaming the Brain. New York: The Free Press

3) OLPC Chemical Imbalance. (n.d.). Retrieved May 2, 2009 from the OLPC Wikki: http://en.wikipedia.org/wiki/Chemical_imbalance

4) (n.d). The “Chemical Imbalance” Myth. Retrieved April 20, 2009 from http://www.psychdrugdangers.com/TheChemicalImbalanceMyth.html

5) Heninger, G. R., Delgado, P. L., Charney, D. S. (January 1996). The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry, 29(1), 2-11.

6) Leventhal, A., Martell, C. (2005). The Myth of Depression as Disease. New York: Praeger.

7) Lachter, B. (December 2001). “Chemical Imbalance”: a clinical non sequitur. Australasian Psychiatry, 9(4), 311-315.

8) Breggin, P., Cohen, D. (2007) Your Drug My Be Your Problem: How and Why to Stop Taking Psychiatric Medications. New York: Perseus Books.

9) Glenmullen, J. (2001). Prozac Backlash: Overcoming the dangers of Prozac, Zoloft, Paxil, and other antidepressants with safe, effective alternatives. New York: Simon and Schuster.

10) Pringle, D. [Review of the book The Myth of the Chemical Cure]. Existential Analysis, 19(2), 423-427. Available from http://www.dianapringle.com/?Published_Articles:The_myth_of_the_chemical_cure.

11) (July 3, 2005). APA admits there is no test for “chemical imbalance”. Retrieved April 20, 2009 from http://www.usanews.net/_archive2006a/00000075.htm

12) O’Meara, K. (2006). Psyched Out: How Psychiatry Sells Mental Illness and Pushes Pills That Kill. New York: Authorhouse.

13) Lacasse, J. R., Leo, J. (2005). Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392. doi:10.1371/journal.pmed.0020392.

14) Fiddaman, R. (September 30, 2007). A Chemical Imbalance- The Serotonin Myth. Retrieved April 28, 2009 from http://www.opednews.com/articles/opedne_robert_f_070930_a_chemical_imbalance.htm.

15) ( March 6, 2008) MHRA Investigation into GlaxoSmithKline/Seroxat. Retrieved May 1, 2009 from www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON014155&RevisionSelectionMethod=LatestReleased.