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How Do SSRI Antidepressants Work?

May 5, 2010

The following chapter, "How Do SSRI Antidepressants Work?" is my edited version of the third chapter of a book by Ann Blake Tracy about the harmful and dangerous effects of Prozac and other SSRI medications.  I edited Tracy's book about Prozac in 2006-2007.  The following chapter is from the (Bollyn) edited version of the book, which has not been published.

Chapter 3
 
SSRI Drugs
 
How do selective serotonin reuptake inhibitor (SSRI) antidepressants work, and what do they do?  Some of the SSRI medications on the market are well known by their brand names, such as Prozac, Zoloft, Paxil, and Luvox.  There are, however, many less well known SSRI medications.
All of these drugs are very similar in action with only slight variations. They were created to specifically affect the levels of an essential hormone that acts as neurotransmitter in the brain, 5-Hydroxytryptamine (5HT), more commonly known as serotonin. Because a lack of serotonin is thought to be a cause of depression, these drugs were designed to chemically raise serotonin levels. In fact, nearly all antidepressants raise serotonin levels, either by increasing serotonin output or by increasing post synaptic sensitivity.
The SSRI drugs have been sold to the public as "new and improved" antidepressants because they have a stronger affect on serotonin levels. Although they have been sold to the public as being more effective for depression than other antidepressants, there is no medical evidence to suggest this. "There is no evidence to suggest that selective serotonergic agents are more effective than other less selective agents in the treatment of depression." (Serotonin In Major Psychiatric Disorders, p. 79).
 
Serotonin
 
Serotonin is the neurotransmitter believed to affect depression and our moods. It is believed to affect pain, REM sleep, sexual desire, etc. It assists in regulating aggression and violence, impulsive behavior, appetite, the drive to act, anxiety, fearfulness, ability to think clearly before acting, judgment, perception, etc. This neurotransmitter, although it has a strong impact upon brain function, is primarily created in the enterochromaffin cells of the intestinal tract.
Serotonin affects nearly every area of brain activity. Serotonin binding sites are found throughout the brain and most predominantly in the raphe nucleus. Projections from these cells ramify to all brain areas, including the frontal cortex, the striatum, and limbic system, affecting the hypothalamus and hippocampus.
"Prozac comes from a world that most doctors don't understand." If you ask a professional, preferably one who is trained in psychopharmacology, the study of drugs which affect the mind, just how the SSRIs work and what the theory behind the mechanics of Prozac was, they will attempt an explanation which usually concludes:  "Actually we really don't know what Prozac does or how it works within the brain or how any other antidepressant works in the brain."
Dr. Peter Kramer, author of Listening to Prozac (1993), said it was "a new and relatively untested drug" and added, "It comes from a world even most doctors do not understand." After admitting that we don't really know just how Prozac does work, the standard explanation goes like this:
Prozac is designed to prevent the re-uptake of serotonin by binding to the cell receptors and the pre-synaptic cell membranes that serotonin normally passes through within the brain. This process is believed to block serotonin so that it cannot pass through into the blood stream where it is quickly inactivated or metabolized. The theory is that this binding effect of Prozac will raise the level of serotonin by holding it in the brain and not allowing it to be expelled. The levels of this neurotransmitter would then begin to build up within the patient's brain.
"What interests researchers is not so much cortisol produced by the adrenals as the substances in the brain that stimulate the adrenals," Kramer wrote. "There is a cascade of such hormones; one brain center stimulates another, and so on down the line until a hormone is released that causes the adrenals to produce and release cortisol. At the top of the cascade is a substance produced in the brain called corticotrophin-releasing factor (CRF). Elevated CRF levels can be measured in the brains of rats subjected to stress - and here is where a more homologous model of stress and depression emerges." (Listening to Prozac, p. 115).
Since researchers first looked at steroids as an answer for mental disorders they have felt that the "stress hormone" cortisol would be discovered to be the biochemical link between stress and depression.  Kramer discusses the importance of stress hormone levels (adrenalin, cortisol, etc.) in depression, suicide and violence:  "Not only depression but also temperament rests on and is sustained by levels of neurotransmitters and stress hormones," he wrote. "Indeed, we should be surprised if a medicine that resets the norepinephrine and serotonin systems does not directly alter temperament." (Listening to Prozac, p. 175)
It should be noted that there is a growing body of evidence to suggest that any drug which affects serotonin will affect the noradrenergic (norepinephrine) system (Frances et al. 1987; Manier et al. 1987; Potter et al. 1985).  This indicates that the SSRIs, which are designed to specifically affect serotonin, will also affect norepinephrine. Therefore, we can be assured that the SSRI medications will alter temperament, including anger and aggression, indeed, any emotion connected to an adrenalin/noradrenalin response.
The SSRIs' effect of raising serotonin levels in turn elevates the body's steroid levels. Now that we have discussed the critical role of body steroids and their connection to depression, we need to understand the role played by SSRI antidepressants.
What Dr. Kramer did not explain, after discussing how depression is determined medically by elevated cortisol levels, is that when serotonergic agents are used to raise serotonin levels, this causes the blood corticosteroid (cortisol, cortisone, etc.) levels to also rise.
This is the case whether it be serotonin precursors (those agents the body uses to manufacture serotonin, i.e. tryptophan), agonists drugs (which produce a release of serotonin), or SSRIs (which block the reuptake of serotonin).
Studies demonstrate that the neurotransmitter serotonin acts as a stimulant of the hypothalmo-pituitary-adrenocortical axis (Fuller 1981), thereby producing excesses of body steroids. Serotonin, if not the specific substance, is apparently one of those substances in the brain that stimulates the adrenals.
Elevated levels of CRF, cortisol and ACTH are evidence of both stress and depression, yet animal studies with SSRIs showed that they increased the levels of ACTH, cortisol and prolactin (Stark et al. 1985; Lesieur et al. 1985 & Jones, Hillhouse and Burden in Frontiers in Neuroendocrinology, Vol. 4).
Studies also demonstrate that serotonin levels correspond with the daily rise and fall pattern of corticosteroid secretion. One single dose of 30mg of Prozac doubles cortisol levels (Petraglia et al. 1984). If one dose causes such a significant increase in cortisol, what kind of increase in cortisol levels can be expected when someone is taking Prozac on a daily basis?
Prozac has also been demonstrated to increase the release of CRF (Gibbes and Vale 1983), suggesting a subsequent increase in ACTH and cortisol levels will follow.  We know that excess cortisol is a marker for depression. Because this was known before Prozac was released, the question is why the drug was ever approved as an antidepressant by the FDA?
This information about the effect of serotonin on body steroids is extremely significant. Taking Prozac or any drug which elevates serotonin levels, in turn consistently elevates body steroids, thereby producing a nonsuppressible pattern of chemically induced elevated cortisol levels.
The increase in body steroids explains many things: It certainly helps us to see how Prozac and the other SSRIs can get someone who is depressed (overwhelmed or exhausted) up and moving. No wonder patients talk about the drug beginning to "kick in" for them as serotonin builds.  This in turn kicks the adrenalin flow straight into high gear.  This is how an SSRI can get a depressed patient up and moving.
Although the patient is up and moving, what should we expect to be the long term effect from using the SSRI method?
We should expect the SSRI medications to produce even greater depression, if not while using the drug, certainly after a period of use.  While taking the drug, the constant adrenalin rush postpones the inevitable "crash." If Prozac is doubles cortisol levels with just one dose, and elevated nonsuppressible cortisol levels are a marker for depression, it should follow that the end result of using Prozac should be a drastic increase in depression. This also helps us to understand why many patients who have never experienced depression before using Prozac report suffering depression after using Prozac and why so many SSRI users report a worsening of depression.
The effect of serotonin in elevating body steroids also gives reason for the "amphetamine effect" felt with the use of Prozac. Cortisol is an adrenalin hormone and adrenalins (epinephrines) are like the body's own version of amphetamines. Adrenaline or epinephrine and amphetamine are chemically related so an increase in adrenalin is similar to a dose of amphetamine.
Prozac and the other SSRIs produce this effect by artificially increasing the level of serotonin which stimulates the adrenal glands to produce more adrenalin – the body's glandular amphetamine.
Prozac or any SSRI should also logically produce the same mental and physical side effects associated with the use of steroids.  The only difference is that the SSRI drugs accomplish this by artificially forcing or chemically increasing the body's own steroid production. We should, therefore, expect the SSRI drugs to cause the same serious physical and psychiatric reactions caused by steroids and amphetamines.
Imipramine, a milder enhancer of serotonin than the SSRIs, reproduces the effects of the amphetamines (Carlton, 1961). The most obvious reason for this is that it increases serotonin, which in turn increases the level of adrenalin.  Any drug which increases serotonin will cause amphetamine-like effects.
Behavioral syndromes caused by amphetamines such as side-to-side head weaving, head tremor, paddling, etc. have been stopped by lowering serotonin. These behaviors are caused by increased serotonin, and serotonin is believed to be the means by which the amphetamines induce these behaviors (Solviter et al. 1978).
Experts have clearly cautioned that the amphetamine effect is a detrimental, ineffective and even counterproductive approach to treating depression. This approach cannot be used without the inevitable "crash" which is the depressive state SSRIs are meant to cure.
When serotonin levels are raised there is a rise, not only in cortisol, but also in prolactin. Excess prolactin can cause headaches, diabetes, or gradual loss of vision. In women specifically it can produce amenorrhea (absence of periods), lactation, or infertility. In men it can produce impotence and breast enlargement.
Logically we should expect the similar result of Cushing's syndrome from the use of the SSRIs. Cushing's syndrome is a chemically induced non-suppressible increase in body steroid production. The SSRIs chemically induce a hyper secretion of steroids - ACTH, cortisol and adrenalin.  Because serotonin stimulates the hypothalmo-pituitary-adrenocortical axis, any drug which increases serotonin should produce the same end result of chemically inducing Cushing's syndrome.
All of the antidepressants in general increase serotonin to some extent. This is the logical explanation for their amphetamine-like effects. Long-term use of SSRIs should result in the same symptoms as Cushing's syndrome. Yet the SSRIs, because of their direct and very potent effect upon serotonin, should produce these effects more rapidly than the other antidepressants.
One of the newer antidepressants, Effexor, produces a double stimulant effect through its indirect effect upon cortisol levels via both elevated serotonin levels plus its direct effect upon noradrenalin or norepinephrine (the adrenaline in the brain and nervous system). It is called "Prozac with a kick." The patient ought to feel as though he has been kicked when the inevitable crash occurs.
Although enabling the depressed patient to get back on his feet, through a drastic rise in adrenalin, it is clear that these drugs actually intensify the symptoms of depression and stress.  Stress, like depression, is measured by excess cortisol. An intensification of the patients' original level of stress is produced by these chemicals by their activation of the adrenergic system.
Dr. Hans Selye, author of The Stress of Life, warned that the body falls into a groove of having an exaggerated response to stressors. This is a kindling process. When a drug stimulates the adrenals, the patient is robbed of his internal glandular control. The adrenals begin to rush at the slightest provocation causing mania, depression, akathisia type reactions (inability to rest or relax, anger, irritability, violence, etc.), hallucinations, electrical surges throughout the body, etc. - all of the symptoms we listed previously which are considered manifestations of stress.
Our bodies normally control excess steroid levels through inactivation in the liver and/or the release of the hormone or neurotransmitter, acetylcholine. As the liver becomes impaired through the use of toxic drugs or as the brain and nervous system lose the ability to produce acetylcholine, the body loses its ability to control its steroid levels.
The first psychotherapeutic medication was Chlorpromazine (Thorazine), an antihistamine. The antihistamines are also known to bring on an adrenalin or epinephrine rush, including the fight or flight response. In fact the amphetamines (a.k.a. "speed") were first developed and marketed for the treatment of asthma. Anyone who has had either a history of street drug use or antihistamine use are prime candidates for a rapid reaction to the SSRIs or any of the other drugs that either stimulate the adrenals or suppress the cholinergic system, or even more so to a drug which does both.
The anticholinergic effects of some drugs impair the ability to produce choline which helps to neutralize excess adrenaline. This inability to produce acetylcholine is the disorder found in Alzheimer's disease. Patient reports on Prozac indicate that both systems, the adrenergic and cholinergic, are being affected.
Why raise serotonin in the first place when it will raise steroid levels and produce a wide variety of mental and physical disorders? We know that the most critical sign of stress is elevated cortisol levels and that elevated serotonin levels produce excess cortisol. Therefore, one thing we can do to avoid this excess stress is to avoid drugs which raise serotonin levels.
Knowing what we do about the connection between elevated serotonin levels and their production of a stress response with accompanying elevated steroid levels should make any of us extremely concerned about using drugs which are intended to elevate or enhance serotonin levels.
The drugs that are used medically to raise serotonin levels are the SSRIs: Prozac (Fluoxetine), Zoloft (Sertraline), Paxil (Paroxetine), Lovan (Fluoxetine), Luvox (Fluvoxamine), etc., the new Effexor (Venlafaxine), Deseryl (Trazodone), Anafranil (Clomipramine), Lithium, BuSpar (Buspirone), Gepirone (congener of buspirone), Ipsapirone (congener of buspirone), Eltoprazine, MAOIs, serotonin agonists and precursors, the tricyclic antidepressants, etc. ECT (electric shock treatment) as well raises serotonin.  
Animal studies demonstrate that in the initial administration Prozac actually causes the brain to shut down its own production of serotonin, thereby causing a paradoxical effect or opposite effect on the level of serotonin. We have no research to verify just how long this shutting down of serotonin production continues.
A decrease in the brain's serotonin levels would indicate the necessity for extreme caution. Lower levels could make drastic changes in a patient's behavior, leading to the reports similar to what we have been receiving from the medical community on Prozac over the last several years. (See medical references in Appendix B.)  "This [shutting down of the serotonin production] should have set off red flags at Eli Lilly," Dr. Peter Breggin told Insight Magazine in April 1991.
To further complicate the paradoxical effect of the SSRIs actually lowering serotonin levels, as the brain works to protect itself from either the drastic depletion or enhancement of serotonin levels, a constant upheaval in the serotonin level results. This rebound action can cause the level to fluctuate up and down bringing on a "roller coaster" effect as the brain fights to protect its neurochemical balance and the drug continues to produce its effect of disrupting the balance.
It is important to keep in mind that whether the level is going up or down, any disruption affecting the level of any neurotransmitter can cause drastic changes in brain function, behavior, mood, memory, sleep patterns and cognitive reasoning abilities. The neurobalance of the brain is very sensitive and the effects of a disruption are extensive. Many effects are long lasting and perhaps irreversible.
"The nervous system is complex and full of redundant pathways, so we should not imagine that a given behavior depends on a single neurotransmitter. Still, a given type of synapse seems to be more important for some functions than for others. Consequently, an excess or deficit of activity at a particular type of synapse may produce altered behavior, even abnormal behavior." (Biological Psychology, p. 81)
 
Diet and Serotonin Levels

Our diet directly affects serotonin levels. The studies which indicate that diet may affect violent behavior (Mawson & Jacobs, 1978) have led to additional studies on how the diet affects serotonin levels. The brain's neurotransmitters are affected by the food we eat. Our nutrition affects our mental health.
While disease and death are difficult enough to face, most people absolutely dread mental disease and insanity. No one would want to risk losing control of their thoughts, mood, and behavior.
Control of our diet can improve our mental health. Our diet directly affects our thoughts, moods, and behavior by providing the nutrients necessary for the production of the essential neurotransmitters. A diet containing artificial additives and sweeteners, pesticides, preservatives, and other chemicals will adversely affect the neurotransmitters – and our metal health. These dietary toxins would include many medications, which interfere with both the production and utilization of neurotransmitters.  (R.J. Wurtman, 1982, 1983; Wurtman J.J., 1985; Wurtman, Hefti, & Melamed, 1981)
It is essential for doctors to carefully examine a patient's medical history in order to see if their depression or other ailments are related to current or prior medications. Doctors need to realize that drugs can interfere with neurotransmitter synthesis and utilization. Patients need time to recover from the effects of previous medication before something is prescribed for depression. 
L-tryptophan is the natural precursor of serotonin. It is an amino acid that is converted to serotonin once it enters the brain. It has been found that foods low in tryptophan decrease serotonin synthesis (Lytle, Messing, Fisher, & Phebus, 1975).  Those with low serotonin levels should increase their intake of carbohydrates, which contain higher levels of tryptophan. Protein-rich foods, on the other hand, inhibit serotonin production by blocking the entry of tryptophan into the brain, and should be avoided by people with low serotonin levels.
Researchers have found that a low protein diet is beneficial. A meal high in protein will cause lower amounts of tryptophan to reach the brain as the other proteins compete with tryptophan for entry into the brain. Carbohydrates increase the flow of insulin. Insulin in turn removes the other proteins from the blood which compete with tryptophan for entry into the brain. In this way carbohydrates increase serotonin production.
Dr. James Wasco, medical writer for Women's Day, warns that we are far too quick in our use of "medication" for emotional problems. The danger in this pill-popping quick-fix thinking is that "all too often" it leads to addiction or dependence as larger doses are required to achieve the desired effect.
Changing one's diet to provide the brain with the proper fuel to balance its own levels of serotonin should be a logical first step to a solution for depression. Over the last several years we have learned that cutting back on our protein intake, especially meats, will lower our risk of high cholesterol, heart disease, cancer, etc. A low protein diet can also help to keep our brains functioning properly, especially when it comes to the production of serotonin.
The standard rule of thumb for good health, physical and mental, is to eat more fruits, vegetables and grains and less fat.  Avoid nicotine, caffeine, and other stimulants and be sure to get the right amount of rest and relaxation. Retiring to bed at an early hour adds more to good mental health than most would imagine. Exercise vigorously several times each week. Whatever you do, do it in moderation.
Faced with the risk of losing control over our mental health, we must be willing to learn a few simple lessons. Nature has a way of alerting us when we ignore the basic rules of life and in this way it prevents us from harming ourselves.
 
NutraSweet and Serotonin
 
The artificial sweetener NutraSweet can lower serotonin levels. The amino-acid tyrosine reduces the amount of tryptophan which crosses the blood-brain barrier for use in the manufacture of serotonin. Foods high in phenylalanine (such as NutraSweet) can pose a serious problem because phenylalanine actually blocks the entry of tryptophan into the brain, thereby also inhibiting the synthesis or manufacture of serotonin.
This is not the only disruption in the neurotransmitter activity caused by phenylalanine. A precursor of dopamine, norepinephrine, and epinephrine (the brain and nervous system adrenalin), phenylalanine can increase the levels of these neurotransmitters while lowering the level of serotonin.
This is an excellent formula for producing agitation and irritability and violence. After ten years on the market, one of NutraSweet's advertisements claimed that it has been "put in everything" and now it is available by the spoonful. The increasing use of NutraSweet could certainly have set many people up for problems involving low levels of serotonin. This information certainly raises questions in my mind as to how NutraSweet was ever approved by the FDA.
It is rare for me to interview a Prozac user who does not drink two to three gallons per day of diet soda containing NutraSweet.  The patients have noted that they were both amazed and confused by their extremely high consumption of these diet drinks. This craving for drinks with a substance which lowers brain serotonin is, to me, a strong indication that the brain is desperately attempting to balance its serotonin level as Prozac causes drastic fluctuations.
Our understanding of the brain, a delicate and extremely complicated organ, and how it works is less than complete.  Why would we risk disrupting the balance of any of its essential neurotransmitters, which could severely affect our sleep and thought patterns, ability to cope, behavior, memory, mood, and cognitive reasoning?
 
Prozac Build-up  
 
Prozac, like other serotonergic drugs, is a highly effective protein-binding drug (94.5 percent), designed, in theory, to block serotonin in the brain for extended periods. But Prozac also binds to other proteins or toxins in the blood, making them too large to be broken down and expelled from the body.
The Physicians Desk Reference (PDR) states that Prozac binds to "human serum proteins, including albumin and glycoprotein. The interaction between fluoxetine and other highly effective protein-binding drugs has not been fully evaluated but may be important. [see Precautions] (PDR 1990, p.905)
Warnings to physicians about prescribing Zoloft discuss some aspects of its protein-binding nature:  "Because sertraline [Zoloft] is tightly bound to plasma protein, the administration of Zoloft (sertraline hydrochloride) to a patient taking another drug which is tightly bound to protein (e.g., warfarin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect."
Keep in mind that a large number of drugs developed over the last few decades are highly protein binding.  For example, the approximate protein binding percentage for Valium is 98%, Halcyon 80%, Xanax 82%, Zoloft 98%, Paxil 98%, etc.
This binding to body proteins and other drugs causes excess stress to be placed on the organs and glands involved in metabolizing and elimination processes, i.e. the liver, pancreas, kidneys, and lymph glands.
The patients who experience extreme adverse effects immediately tend to be those who are mixing Prozac with other drugs, those with pancreatic, liver and kidney weaknesses, those in a weakened physical condition, or those with a past history of diseases affecting these organs, including a past history of excessive alcohol usage or drug abuse, or years of prescription drug use, especially psychoactive drugs or drugs which induce psychiatric side effects.
 
Prozac and the Liver
 
"Fluoxetine [Prozac] is extensively metabolized in the liver," Eli Lilly states in their clinical pharmacology warnings about Prozac. "As might be predicted from its primary source of metabolism, liver impairment can affect the elimination of fluoxetine.
"This suggests that the use of fluoxetine in patients with liver disease must be approached with caution. If fluoxetine is administered to patients with liver disease, a lower or less frequent dose should be used," Lilly says.
It is a frightening observation that one of the more frequent complaints of adverse reactions made to the FDA about Prozac is "impaired liver function". The signs of impaired liver function, which should be watched for to prevent severe malfunction are:  nausea, vomiting and abdominal pain.
The liver is one of the most important chemical processors of the body. One's energy level is dependent on the liver's capability to function properly and remove residual chemicals and toxins.  Every biologic process leads to chemical changes and proper liver function is necessary to process these chemical byproducts. These products should be soluble to facilitate their elimination. 
When the process of elimination is quick, and recovery complete, our tissues undergo little change and we remain healthy and young. There is, however, a percentage of all biologic reaction products that are insoluble, or less rapidly removable than their rate of production. Cross-linked proteins, chemicals, calcium deposits, and other products of biologic activity would be included in this category.
This accumulation interferes with the liver's ability to manufacture vital hormones and enzymes, the ability to neutralize poisons, and control steroid production. This, in turn, affects the immune system, blood pressure and heart function, brain, kidney and pancreas function. The effects on the vital organs can cause serious damage to the entire system and shorten one's life.
"Mere excessive accumulation suffices to block the machinery," Dr. Selye writes in The Stress of Life. "It could induce the changes we consider characteristic of aging by the mere presence of ever larger amounts of inert waste products and the consequent inability to produce indispensable vital ingredients at the proper rate." (The Stress of Life, p. 431)
Liver impairment as a consequence of using antidepressants and many other medications is a serious concern. If a patient is taking a drug which impairs the organ essential in controlling the amount of medication the body retains in the blood, how safe can the drug be? Once liver function is impaired, any chemical can accumulate rapidly within the body to toxic levels, producing adverse reactions and even death.
The pharmaceutical product warnings on Prozac in May 1990 mentioned the possibility of the drug precipitating hyperglycemia (diabetes), hypoglycemia and pancreatitis. The adverse effects on the pancreas appear to be causing an imbalance in blood sugar levels which in turn cause a compulsive desire for alcohol, processed sugars, and stimulants like cola drinks, nicotine, and other drugs.
These substances can further impair liver function, increase the chances of drug interaction, and cause the pancreas to over-react because of the additional stimulation. The body's desperate attempt to increase the blood sugar by these means could impair liver function, which would cause the level of Prozac in the system to rise to dangerously higher levels. Thus the vicious cycle of this drug would become self-propelling and self-defeating.
The undue stress placed upon the pancreas, even to the point of pushing the once healthy pancreas into malfunction, would cause the excessive craving for stimulants which could further impair liver function.
Combine this with the high incidence reports to the FDA of liver impairment as a reaction to Prozac and we should question anyone's ability, no matter how healthy, to withstand the effects of this drug over a prolonged period of use. The amount of time before the adverse side effects, both emotional and physical, become manifest is an indicator of the strength of the patient's constitution.
 
Prozac Forever?
 
"The effectiveness of Prozac in long-term use, that is for more than 5 to 6 weeks, has not been systematically evaluated in controlled trials," The Physician's Desk Reference says.  "Therefore, the physician who elects to use Prozac for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient."
The vast majority of patients on Prozac have been on the drug for far more than 5 or 6 weeks and few have been "periodically re-evaluated." Most doctors assume there is no need to do so, either because the sales pitch they received did not include warnings of possible side effects or because the doctor's work load allows little time to investigate the huge number of new drugs on the market.
The importance of consistent re-evaluation has evidently not been stressed to physicians by the pharmaceutical reps, because close monitoring of Prozac is very rare. In fact, it is amazing to see how often the suggestion is made that a patient may need to stay on Prozac indefinitely – even for life.
In medical school, doctors receive little training on drugs.  It would make far more sense for doctors to diagnose and pharmacists to prescribe the drugs since they know so much more about them. Unfortunately, it appears there are far too many irresponsible health professionals who, due to lack of knowledge, have little concern for the adverse effects their patients experience with Prozac. Much of this stems from their lack of education about drugs and drug reactions. David Rothman reviewed Listening to Prozac in February 1994 for The New Republic and addressed this issue:
"To the extent that Kramer is typical of his generation of physicians, it is plain that trusting the medical profession to be strict gatekeepers before therapies, new or otherwise, is foolhardy," Rothman wrote. "Anybody who expects physicians to save us from ourselves, or from the worst imaginable abuses of twenty-first-century medical interventions, whether they involve genetic engineering, pharmacological interventions or surgical procedures, had better start searching for alternatives."
The attitude of the mainstream medical community is that Prozac does not have serious side effects: "This is a wonderful new drug with no side effects," they say. "Try it. You will feel great."
The patient rarely gets the follow-up call. Instead, the doctor often says, "Here is your prescription for the next year. Unless you notice any problems, we will see you then." In this way the responsibility is put on the patient and not the doctor.
If the drug did not alter the mind and impair one's judgment, the doctor might rationally expect that the patient would notice developing problems, but few former Prozac patients will claim to having been capable of judging whether or not they were having problems with the drug.
If they did suspect Prozac was affecting them adversely, they were afraid to tell their doctor because they felt they would not receive the assistance needed to discontinue Prozac use or face the terrible withdrawal. And they often say that they are afraid the doctor would accuse them of having "pre-existing emotional problems," rather than recognizing that their problems are caused by Prozac. This is often cited as one of their fears even if the drug was initially prescribed for a physical, rather than a mental or emotional ailment.
 
Prozac for Weight Loss?
 
Why did Eli Lilly and Company have problems gaining FDA approval of Prozac for weight loss? Is Prozac a safe way to lose weight? Eli Lilly has sought to obtain FDA approval for the use of Prozac, with a brand name change to Lovan, as a treatment for obesity – which is often caused by blood sugar imbalances, as demonstrated through obsessive appetite cravings.
If Prozac is approved as a weight loss remedy we may experience a nightmare beyond our wildest imaginations. A contributing factor to the nightmare would be the extremely high dosage suggested for weight loss, 60 mg. or three times the normal dose.
Even though Prozac has not been approved for obesity there are weight loss programs that recommend it and doctors who suggest that weight loss is a beneficial side effect.
It is important to understand how this is achieved.
First, it is understood that Prozac speeds up the metabolism, causing it to work beyond its normal capacity in the same way amphetamines speed up the metabolism. Many patients report the "crashing" of the metabolism after discontinuing use of the drug. This causes an inability to digest food properly causing gas problems and weight gain.
Research suggests that the other method of producing weight loss is through poisoning. When an individual becomes extremely toxic from high amounts of poisons lodged in his body, he instinctively goes into a fasting or semi-fasting state in order to flush out those poisons. This is an instinctive life-saving reaction.
Eli Lilly uses serotonin double talk to explain how Prozac causes weight loss. However, when a highly accumulative drug needs to be increased to three times the average dose in order to be effective, it should be obvious that the patient is losing weight by going into an anorexic state as a reaction to being poisoned.
Nearly 10 percent of Prozac users reportedly develop the serious eating disorder of anorexia.
 There are certainly better ways to achieve weight loss, as Dr. Merton Kahne, professor of social psychiatry at MIT, told the Long Island Newsday on July 3, 1990.
 Kahne was involved in clinical trials comparing fluoxetine [Prozac] and another serotonin stimulating drug called dexfenfluramine in overweight but otherwise healthy people.
"My general impression is that the anorexic effects are dose-related and that it is risky to prescribe Prozac given the current state of knowledge," Kahne said. "It is likely to turn out that at the lower doses, you may only get a slight weight loss. To get a more significant effect, you may have to overdose the person.
"Using Prozac to treat weight problems is like shooting a mouse with an atom bomb," Kahne said.
An article published in Business Week, entitled "Prozac is Making Lilly a Little Edgy" (June 22, 1992)discussed Lilly's plan to market Prozac for weight loss under the name Lovan. The article was not optimistic. It should be noted that "increased appetite" is one of the side effects of Prozac listed in Lilly's literature.
The adverse paradoxical reactions are due to toxicity. People who reach toxic levels of Prozac in their systems suffer adverse paradoxical reactions. Those who have suffered these severe adverse reactions are now dead, either due to violent acts taken against themselves or fatal physical reactions, or they are being prosecuted for violent actions they took against others, or they have survived with their lives shattered - mentally, physically, emotionally, and financially.
 
"Prozac Hell"
  
Long-term users of Prozac live in this so-called "Prozac Hell" and are the saddest victims of all. They describe themselves as:
 
extremely irritable;
experiencing overwhelming rages with an intensity they have never felt before which forced them do things they "didn't want to do";
focusing this rage on someone they have cared about, even to the point of stalking them;
having violent suicidal or homicidal thoughts;
having no feelings of guilt or sense of conscience;
experiencing addiction or dependence;
having panic and anxiety attacks;
feeling "possessed";
developing an "I'll show you!" attitude toward everyone around them;
having no memory of who they are;
having their memories become so jumbled and confused that they are   producing "false memories" of an innocent loved one abusing them;
putting on the appearance of being normal while having horribly bizarre thoughts;
experiencing obsessive compulsive behaviors such as sex, spending, shop-lifting, embezzling, etc.;
losing the ability to read, learn or retain information;
having extreme difficulty with concentration;
having no ability to feel love or concern for those close to them;
having impaired judgment (forming a thought sequence to arrive at a decision becomes a monumental task);
feeling completely out of control and developing an overwhelming fear of being controlled by others.
 
For these victims it is a devastating thought to admit such obvious "out of character" behavior. They fear that they will be labeled "crazy" because they realize the things they have done are insane. They have never experienced anything like it before and are overwhelmingly shocked, embarrassed,  and puzzled by their own behavior.
 
 Toxicity Syndrome
 
Dr. Breggin explains the toxic reaction to Prozac in an article from The Rights Tenet, 1992 Winter/Spring:
 
"Reports by Prozac survivors present a consistent pattern of compulsively driven thoughts and activities, especially suicidal and violent behavior. Typically the behavior is 'out of character' for these individuals who become hostile, paranoid, euphoric, energized, hyperactive, undisciplined, unable to sleep, subjectively grandiose and omnipotent, and insensitive to the effects of their behavior on themselves or others. Racing thoughts of 'a mind that won't stop going' are typical. Periods of 'crashing' and depression are common. Short-term memory and attention span are almost always impaired. Much more rarely patients become frankly confused and disoriented. Cognitive and emotional difficulties often persist after stopping the drug. Addiction and withdrawal symptoms are common, including severe depression and a worsening of suicidal or violent impulses.
During the drug reaction, individuals do not realize that they are behaving abnormally, but later they may be appalled by their actions. Afterward, they frequently cannot clearly recall their actions."
 
This toxic reaction is an emotional nightmare - a mental and emotional "living hell". The symptoms are emotional in appearance, stemming from a chemically induced brain disorder. The toxic reaction is not showing up as a physical malady, but in thinking processes and behavior. Patients do not realize how they are acting while under the influence of the drug. In my opinion the "lucky" ones are the patients who suffer an obvious physical reaction forcing them to go off the drug before they suffer the Prozac Toxicity Syndrome which profoundly affects their mental state.
The patients' unfamiliar emotions and unacceptable actions, for which they assume they should accept responsibility, along with the utter confusion, bring on such feelings of humiliation, inadequacy, and loss of self-respect that the patient becomes even more depressed about their situation. He or she continues to take the medication or even accepts an increase in dosage, thinking that he really needs this anti-depressant.
The most heart-rending side of Prozac is that the patient, who is uninformed of the side effects, is led to believe that all these feelings and events are indications of flaws in his own character and not reactions to the drug.
The problem is blamed on the victim, not our latest cure-all.
"Prozac is a boon to psychiatrists. It brings in business!" Michael O'Brien of the Citizen's Commission on Human Rights said. "A person with a simple problem now becomes a mental patient with serious problems."
The patients that are being convinced that they are not actually suffering a chemically induced psychotic reaction, but really are going crazy, generally become long-term mental patients. They suffer years of additional psychoactive drug therapy with each new drug, multiplying the toxic effects.  Electric shock treatments, antipsychotic agents, anti-seizure medications or hospitalization follow.
Attorneys are asking what they should do with the flood of people that come to them. They say the patients are afraid to go back to their doctors because the doctor will either raise their dose, thinking they need more of the drug in order for it to be "effective," or will label them "crazy" or "suicidal" and have them committed to an institution.
 
Serious Side-effects
 
There are serious physical side effects to Prozac use.  Generally the physical side effects are more easily recognized than the emotional ones. Unfortunately, many doctors are completely unaware of the physical reactions to the drug. After diagnosing the physical condition, they don't even see the connection to Prozac. 
Without discontinuing the use of Prozac, the doctors prescribe additional medication for the drug-induced symptoms brought on by Prozac. This further complicates the patient's condition and greatly increases his chances of adverse drug reactions or interactions.
"Prozac not uncommonly causes nausea, loss of appetite, nervousness, insomnia, drowsiness, fatigue, sweating, rash, dizziness, and headache. More rarely, it has been associated with damage of one sort or another to almost every body system and organ - from arrhythmia of the heart to inflammation of the liver to dysfunction of the thyroid gland," to Dr. Kramer wrote in Listening to Prozac. (Listening to Prozac, p.311)
Some patients report vomiting blood. Terrible burning pains in several organs are reported regularly by ex-Prozac patients: the pancreas, gall bladder, kidneys, stomach, spleen, etc.  Several have lost at least one of these organs. Unfortunately, excess adrenalin flow sometimes prevents the surgical wounds from healing properly and the patient has to endure repeated surgeries.
The pain is almost always reported as "burning". Occasionally it will be a stabbing pain in the same organs. Often urine is reported as "burning."  One patient reported such a severe burning from her urine that cold compresses after urination became necessary. Doctors rarely discover the cause of the burning sensation.
 
Doctors Defend Drugs
 
Why do doctors have such a need to defend drugs? Does it somehow validate the value of their profession because if we didn't need drugs, perhaps we would no longer need them to supply those drugs?
Many doctors tell their Prozac-using patients who have developed complaints such as seizures, hypoglycemia, diabetes, cancer, pancreatitis, rashes, bronchitis, kidney problems, blood platelet disorders, and liver abnormalities, that Prozac had nothing to do with their ailments although there is an abundance of medical evidence linking these symptoms with the drug.
Why wouldn't a doctor immediately discontinue the use of a medication when serious drug reactions occur in their patients?
It is a mystery why doctors feel such a need to defend drugs. Their responsibility is to help their patient, not a drug company.  Past mistakes with drugs should have taught them a lesson.  Are doctors so busy that they don't have time to read the information on the new drugs they are giving their patients or are they using mind-altering drugs themselves and having trouble thinking clearly?
Contrary to popular belief, a physician is only human and just as likely as any one else to make mistakes.  A doctor's mistake, however, may cost a life or cause permanent damage.
Patients and doctors alike should learn more the substances we are ingesting and how they affect our bodies and our minds. We must take responsibility to think for ourselves and stop expecting others to do it for us.
How bad do things have to get before we wake up and take back the responsibly which is rightfully ours? No one has more insight into what is happening within our own bodies than we do.  Our health is our most essential obligation, because without it we cannot function.
Another serious potential problem involving the physical side effects of Prozac is that the drug is very often prescribed as a painkiller because of its anesthetic type effect. It is given for headaches, chronic pain, post-surgical pain, etc.
Some patients report having cut themselves just to see if they are still capable of feeling pain. (Rarely do patients mention feeling pain when they mutilate their bodies.) Therefore, as the patient is using a painkiller on a regular basis, he remains unaware of ongoing or developing physical conditions because his internal alarm system – awareness of pain – is blocked.  
 
Serious Physical Side Effects
 
Many patients, as they are finally beginning to come off the drug after prolonged periods of Prozac use, are finding they have developed several physical ailments, some very serious. They have unexplained aches and pains that were not there before or that have become more intense since the use of Prozac. They have remained unaware of these ailments during the use of the drug because they could not feel the pain associated with the developing disease.
With the increasing long-term use of Prozac, patients are continuing to report additional problem areas in physical side effects that need to be evaluated.

The following side effects are listed in The Physician's Desk Reference, Family Guide to Prescription Drugs when using Prozac: heart attack, impotence, hair loss, cataracts, kidney disorders, hepatitis, arthritis, breast cysts, breast pain, convulsions, coma, migraine headache, bronchitis, pneumonia, deafness, duodenal ulcer, stomach ulcer, gallstones, pelvic pain, inability to control bowel movements, painful sexual intercourse for women, urinary tract disorders, eye bleeding, spitting blood and vomiting blood.
  
As Prozac is the common denominator in all these reports and many of the complaints are identical, there is strong indication that many of these ailments are brought on by use of the drug. The large majority of these complaints correspond to the side effects produced by steroids or amphetamines. People should be aware of the following physical reactions to Prozac:

         Drastic rise in blood pressure and cholesterol levels, severe loss of memory, hair loss, sleep disorders, headaches, joint pain, muscle contractions, sweating, nausea, severe abdominal pain (often a burning pain), kidney pain and kidney failure, burning urination, hypoglycemia, diabetes, abnormal liver function, development of various allergies, rashes, development of Chronic Fatigue Syndrome symptoms, chronic digestive problems including poor metabolism, indigestion, gas and diarrhea, ulcers, blurred vision, electric surges shooting throughout the head and body (similar to what is known as "post drug syndrome"), slurred speech, adrenalin rushes at the slightest provocation, seizures, sexual dysfunction, bloating and weight gain, endless ringing in the ears, burning or tingling in feet or legs, swelling in joints, heart flutter, and heart attacks.
 
Bloating - One of the most obvious of glandular dysfunctions is the rebounding of the metabolic processes which have been sped up by Prozac. Far too many experience bloating and flatulence as the system shuts down its processes and the patient discovers his inability to digest.
Male and female patients alike give the appearance of being pregnant as their bellies and abdomens become extended by the gas - a clear symptom of Cushing's syndrome. Then they begin to accumulate excess weight from the inability to digest and process the food. Many patients report these digestive problems after their Prozac use.
Weight lifters and those seeking to lose weight have been told that Prozac will speed up the metabolism. This accelerating of the metabolic processes is produced by stimulant drugs. After being forced to perform beyond its capacity for an extended period of time the metabolism appears to shut down or "crash" along with the other body systems.
 
Blood platelet disorders - An area of great concern is that of blood platelet disorders. Patients are reporting that after using Prozac their white blood counts, as well as red blood counts, are low.  Some of these blood disorders are "terminal."
Suzanne Johnson of Atlanta, Georgia testified to the FDA in September of 1991, warning that something must be done about Prozac or the blood of many more victims would be on their hands. Suzanne died a year later in November, 1992 of a blood disease listed as a side effect of Prozac where the patient can no longer produce their own blood. Johnson was transfusion dependent for over a year and a half before she died.
Johnson, like many others, did not live long enough to fight a legal battle with Lilly. Richard Kapit, an FDA reviewer of Prozac, recommended product labeling for the drug to include warnings to physicians "that certain signs and symptoms of depression may be exacerbated by this drug."  
"Patients exposed to this drug show higher rates of reduced hemoglobin," Kapit said. The drug also caused "a fluoxetine-induced elevation of LDH." Kapit felt further testing was necessary to determine the severity of these risks. Another antidepressant, Tegretol, causes an irreversible drop in the production of white blood cells.
 
Cancer and tumors – A Canadian study (Cancer Research, July 1, 1994?) has shown that the antidepressants Elavil and Prozac are tumor promoters:
 
"[A]mitriptyline and fluoxetine inhibit normal lymphocyte proliferation in vitro and promote tumor growth in three out of three...fluoxetine (20-40 mg/day) has been associated with 21 reported cases of reactivation of herpes... suggesting that even at the lowest range of prescribed doses, it can impair normal human immune function in vivo."
 
It also demonstrated that Prozac was "more potent than amitriptyline" in promoting tumors. When we understand the effects of these two drugs upon serotonin, with Prozac being the more potent of the two, and the subsequent increase produced by serotonin of body steroids, we can see why Prozac would have more adverse effects on the immune system.
The study shows that the drugs accelerate the growth of tumors. Lorne Brandes, the oncologist from the Manitoba Institute of Cell Biology in Winnipeg, who led the study, feels that the tumor growth is being promoted by these drugs binding to the intracellular histamine receptor.
If this is the case, it raises the questions about the antihistamines and cancer as well. This information will have a great impact upon a physician's decision to put a cancer patient on antidepressants and could change the standard procedure of placing post-operative patients on antidepressants at a time when the immune system is most vulnerable.
There have been additional reports of accelerated growths, such as endometriosis. One patient who underwent surgery to completely clean out her endometriosis surprised her doctor a year later when he opened her up to find her completely full of endometriosis again. She had been on Prozac for two years.
 
Immune System
 
The obvious conclusion to draw from the reactions mentioned above, is that Prozac causes a strong adverse reaction on the immune system, as so many of our new wonder drugs also appear to do. When the cortisol levels are doubled with just one dose, this type of adverse reaction with the immune system should be expected. Using many of these drugs which cause stress responses from their toxic effects over several generations would naturally cause us to build up a tolerance level which would require larger doses to accomplish what lower doses have done in the past.
All of these new drugs have such a highly increased potency in order to achieve the results we used to achieve with milder doses. This has an adverse impact on our immune systems. Beyond the risk it would pose for a healthy individual, Prozac's effect upon the immune system should be a clear message, a warning, to those taking Prozac for Chronic Fatigue Syndrome or AIDS or any other disease, which involves disorders of the immune system.  Prozac should accelerate these diseases. At what rate it does that, however, remains to be seen. Prozac is often prescribed by physicians for these diseases because of its energizing or stimulant effect.

Lupus and Fluoride
 
The diagnosis of chemically induced Lupus has become so common that a special support group for those individuals has been formed, PAIN, headquartered in Hawaii. A woman who attended my lecture told me, "After doctors being baffled for quite some time, I have just been diagnosed as having Lupus. I have never been on Prozac, but all of the reactions you speak of are almost identical to my symptoms."
She stated that the only difference in her life before the symptoms appeared was the use of a natural product, blue-green algae. When I asked if algae had been grown in heavily fluoridated water, she said she didn't know, but would find out.
My curiosity as to whether the fluorine molecule in Prozac might be breaking loose from the Prozac compound to produce many of these adverse reactions had been aroused nearly two years before this.
The woman's voice was full of excitement when she called me early the next morning to inform me that she had looked through her information she had been gathering on this particular brand of algae and had found that it was indeed extremely high in fluoride concentrations.
She immediately informed her physician of the discovery of this toxic chemical connection to her symptoms. Anyone wanting to follow up on the psychiatric effects of fluoride may want to refer to "What Looks Like a Neurosis May be a Fluorosis." (Forman, 1963)
 
"Burn Out"
 
Long term, latent or tardive effects appear with Prozac. The type of "burn out" seen with stimulant type drugs is being reported regularly in conjunction with Prozac. I had four people within four blocks of my home who lost their jobs because of physical and mental disability from using Prozac at least two years.
One had lost her ability to read or write and moved her children back to live with her parents until she could recuperate. Another was in a drug-induced stupor, unable to cope with anything. Her children had lost their mother when a doctor prescribed Prozac after a divorce. She had been a vibrant, happy, good mother.
The third person was unable to focus clearly enough to write the reports necessary in his type of employment. The fourth person worked in an emergency medical position and had been given Prozac to cope with the death of her sister from cancer. She became so physically ill from the adverse effects of Prozac that she nearly lost her own life. She became unable to handle her job, but after two years being off Prozac and many alternative treatments to restore her health, she was able to work again.

Tardive dyskinesia
 
A serious concern with any of the psychoactive drugs should be tardive dyskinesia. Although it took years for the medical profession to acknowledge this drug-induced disorder, the American Psychiatric Association figures predict half or more of elderly patients or long-term users of psychoactive drugs will develop tardive dyskinesia.
This is an impairment of voluntary movement resulting in fragmentary or incomplete movements, involuntary and uncontrollable muscle twitches or contractions. The body muscles contract throwing the whole body into spasms. Legs and arms fly about and heads bob around and up and down as if they were puppets with someone violently jerking the attached strings.
The facial muscles contract causing grotesque facial grimaces and contortions, involuntary protrusions of the tongue - all those gestures we have come to associate with mental illness, but which we now know are side effects of the mind-altering drugs the patients have been taking for years.
Dr. Breggin uses as a standard rule of thumb, there is a 5% increase in the possibility of the development of tardive dyskinesia with each year of psychoactive drug use. For the elderly and chronically ill the percentage is closer to 25% per year chance of developing this disabling adverse reaction.
If this is an outward manifestation of what is happening within the brain itself, what types of involuntary actions and disruptions are happening within the brain?
Tardive dystonia is closely associated with tardive dyskinesia. It is described as a condition wherein muscles tense up or contract involuntarily.
Involuntary muscle contractions of Prozac patients are often reported and could develop into either of these serious and apparently permanent disorders. Many lawsuits involving this side effect have been filed against Lilly.
Prozac apparently causes these conditions more rapidly than did previous drugs. An Iowa woman took the Prozac for only eight days before she began to experience severe muscle spasms in her arms. Two and a half years later she still has tardive dyskinesia. A Texas woman sued because of suffering permanent neurological damage after taking two capsules of Prozac a day for a total of only two days.
Dr. Kramer acknowledges this very real possibility with Prozac: "Psychotherapeutic drugs can sometimes cause tardive neurological disorders, which may appear years after a drug is discontinued; and questions have already been raised whether Prozac can cause such syndromes...Concern over unforeseen or tardive effects is realistic, because Prozac has been around too briefly for anyone to know its long-term effects." (Listening to Prozac, p. 312)
Tardive akathisia is another serious latent disorder, believed to be associated with tardive dyskinesia, which should be considered the most dangerous and tragic of any of the long-term effects.

Parkinson's disease
 
Parkinson's disease is another motor disability that can follow the use of psychoactive drugs. Unfortunately depression is generally associated with this disorder as well. Dr. Ernst Jansen Steur of Holland conducted a study published in January 1993 on the increase of motor disability in Parkinson's patients in conjunction with Prozac.
The most frequently increased symptoms were: tremor at rest, fingertaps, hand movements, and body bradykinesia which is an abnormal slowness or sluggishness of physical responses. Because the increase in symptoms was transient and was reversible after the withdrawal from Prozac, it was concluded that it was Prozac induced rather than a natural progression of the disease process.
In none of his patients was depression substantially alleviated by Prozac while "Parkinson disability definitely increased." Dr. Steur concludes that "The increase of Parkinson disability after fluoxetine exposure can easily be explained on the basis of a dopamine-antagonistic activity of fluoxetine." (Steur, 1993)
 
Panic attacks, anxiety attacks and adrenalin rushes are also very common post drug effects reported in conjunction with the use of Prozac and the other SSRIs. It is my opinion that all of these latent or after effects are closely intertwined and produced through similar means.

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