Psychiatry and the Psycho-Pharmaceutical Complex, FDA, Drug Industry, NIMH, NAMI

		What Is Prozac & How It Works Selective Serotonin Reuptake Inhibitors by Peter Breggin, M.D.

(The excerpts here are taken from Chapter 2 of Peter Breggin's book, Talking Back To Prozac.) The book contains a tremendous amount more information about the shoddy methods used to "prove" the efficacy of Prozac, the politics of the drug industry, approval of dangerous drugs, and the dangers of Prozac. We recommend this book to anyone considering the use of this dangerous drug.

Prozac, and a group of closely related drugs including Zoloft and Paxil, belongs to a new generation of antidepressants that were engineered in drug company laboratories. The drugs are called selective serotonin reuptake inhibitors, or SSRIS. The name provides guideposts for discussing its impact on the brain. We'll begin with serotonin.

Serotonin ⁽¹⁾ is a neurotransmitter - a chemical produced in nerve cells (neurons). Serotonin was discovered in the body and then in the brain in the mid-1950s. Ten years later, in 1964, specific serotonin-containing nerve cells, or neurons, were located in the brain. Further investigations identified serotonin as a neurotransmitter or messenger between brain cells.

A very simplified Diagram A depicts neurotransmission at a serotonergic nerve synapse. Serotonin (labeled as S) is made in the nerve and then released from the nerve ending into a small cleft or space (synapse) between the nerve ending and the next nerve in line.
The serotonergic nerve is called presynaptic because it deposits the neurotransmitter (in this case, serotonin) into the synapse. The nerve on the other side of the synapse is called postsynaptic, because it receives the neurotransmitter. Serotonin, as it crosses the synapse, acts as the chemical messenger between the two nerves.
After it is released into the synaptic space, the serotonin must connect to special serotonin receivers, called receptors, on the surface of the postsynaptic nerve. Once the connection is made, the postsynaptic nerve is fired.
Packets of serotonin, released into the synapse, can be metaphorically compared to sparks. The receptors on the postsynaptic nerve can be compared to flash pans full of gunpowder, waiting to receive the serotonin spark.
Brain function is very complicated and little understood and, in addition to neurotransmitters, a variety of other substances also affect nerve transmission. While we don't know how many neurotransmitters exist, 100 or

more substances have been identified that control neurotransmission, and many of them are neurotransmitters. Dopamine, norepinephrine, acetylcholine, and serotonin are among the well-studied ones and are often affected by psychotropic ⁽²⁾ drugs. Nerve cells are classified and named according to the neurotransmitter that they manufacture and release. T'here are, for example, dopaminergic, cholinergic, adrenergic (norepinephrine), and serotonergic nerves.

How Prozac Works: Blocking The Reuptake Process

Neurotransmitters remain in the synapse for only a brief period of time before they are used, destroyed,t or returned to the presynaptic nerve cell for further use. When the neurotransmitter is taken back up by the nerve for reuse, the process is called reuptake, or simply uptake.

Prozac blocks or inhibits the reuptake process for serotonin. The result is an increased amount of serotonin in the synaptic space and a longer duration of action. In effect, more "sparks" are allowed to remain glowing in the synapse. With more serotonin remaining active in the synapse, presumably there will be increased @g of nearby postsynaptic nerves.

Biopsychiatrists theorize that blocking the uptake of serotonin from the synapse increases serotonergic neurotransmission and that this is good for the brain and mind, leading to the improvement of mental disorders, including depression. The theory is based on research and speculations suggesting that sluggish serotonergic nerve transmission is a cause of impulsivity, including violence and suicide. The theory itself is somewhat confusing and contradictory, because it's difficult to conceive of depression as an expression of "impulsivity"; but the theory tries to link together a variety of behaviors or conditions, especiaffy violence, murder, depression, and suicide. Sluggish serotonergic nerve activity is supposed to worsen or cause that entire cluster of destructive tendencies.
Meanwhile, is there evidence that causing serotonergic nerves to become more active can help people to overcome emotional problems? Very little. Almost all the research is about sluggish serotonin, not normal or hyperactive serotonin.

It is presumed that blocking reuptake of a transmitter automatically leads to the "enhancement" of nerve function, but this conclusion seems highly unrely. It is much more likely that blocking the normal regulatory activities of the brain would produce widespread dysfunction.

The Supposed Selectiviity of Prozac

Prozac, Zoloft, and Paxil are described as "selective" uptake blockers. That is, they are supposed to impact on serotonergic nerves with little or no spread of effect to other neurotransmitter systems or other brain functions. This is an important claim because the promotion of Prozac has centered on the concept that, unlike other antidepressants, its effects are relatively limited by virtue of its selective inhibition of serotonin reuptake. In encouraging patients to take the drug, psychiatrists often follow this promotional line, explaining that "Prozac is different. It affects only serotonin." Almost everyone who takes Prozac or any SSRI has heard this.

For many reasons, this claim of selectivity is very misleading. The SSRIS, in fact, end up heavily impacting other neurotransmitter systems. Prozac, for example, has been shown to stimulate indirectly the adrenergic neurotransmitter system, resulting in significant, widespread compensatory changes within the receptors of that system. One of Prozac's most menacing side effects, as we shall see, is probably due at least in part to its effect on yet another neurotransmitter, dopamine.
The emphasis placed on selectivity for the serotonergic system can further mislead people, including physicians, who do not realize that serotonergic nerves spread like a branching tree throughout the brain and spinal cord.

Every neuron is made up of a cell body, dendrites

(receptive extensions from the surface of the cell body), and an axon. The axon is a slender filament that reaches out to other neurons and their dendrites and axons to make synapses with them. Some axons are infinitesimally short and some are long enough to extend around much of the brain or down the spinal cord. As depicted in Diagram B above, the serotonergic cell bodies lie clumped in the raphe nuclei (a collection of cell bodies) deep in midbrain, but their axons reach into nearly every comer and crevice of the brain and down the spinal cord, where they affect a wide variety of other nerves that control bodily functions. Serotonin is, in fact, the most widespread neurotransmitter system in the brain.

In the process of spreading throughout the brain, serotonin nerves help to regulate every major functional region, including the cerebral cortex, frontal lobes, hmbic system, basal ganglia, cerebellum, and hypothalamus. Through the hypothalamus, the system also affects the pituitary gland. Serotonin, therefore, affects many other systems in the brain, including those that produce endorphins, thyroid hormones, corticosteroids (cortisol), and sex hormones.'
The serotonin system is the most widespread neuro-transmitter system in the brain and, because of this, Prozac impacts on the entire brain. The chart on pages 2729 lists, in simplified form, some of the central nervous system functions potentially affected by Prozac. The chart corresponds to Diagram B to show the location of the various brain functions within the serotonergic network. WUle very schematic, the point is accurate: Serotonergic nerves influence the function of the entire brain and mind, and hence the whole person.

Serotonin also plays important roles outside the brain and spinal cord. It was first isolated in the blood, and its name reflects the constrictive action it was found to have on blood vessels. Scientists are not even close to unravefing serotonin's various roles in bodily function. According to a review in the Phannacological Basis of Therapeutics, "5-HT [serotonin] both stimulates and inhibits nerves and smooth muscles in the cardiovascular, respiratory, and gastrointestinal systems."

Prozac has been shown to interfere with the functions of serotonin throughout the body, including the'platelets in the blood, accounting in part for its wide variety of side effects.

Overall, Eli Lilly's promotional line about Prozac's selective effects on the nervous system should be viewed with caution and skepticism. No one prescribing or receiving the drug can fully grasp Prozac's overall impact on the brain and whole body, because it's beyond our current scientific understanding.

Effexor: Back to the Future

Now that Prozac, Zoloft, and Paxil have claimed a position of superiority by virtue of selectively impacting on the serotonergic system, we already have a promotional backlash. Effexor (venlafaxine hydrochloride) was approved by the FDA in December 1993 and is now available (spring 1994); it will be marketed as "Prozac with a

Area Where Located Effects of Dysfunction
*Area*	*Where Located*	*Effects of Dysfunction*
Raphe Nuclei	Deep within the brain	This is the origin for the nerve cells that make and release serotonin. The extensions (axons) of serotonergic nerves spread throughout the brain and into the spinal cord. Prozac and other SSRIs disrupt the function of all serotonergic nerves.
Cerebral Cortex	Outer surface of the brain	Dysfunction within the cerebral cortex impairs higher mental activities, including intelligence and sensory perception.
Frontal Lobes	Front of the brain	Dysfunction within the frontal lobes impairs reason, impulse control, ability to make future plans, empathy and social awareness, insight and judgment-in short, the most human functions.
Limbic System	Widespread, beneath the frontal lobes	Dysfunction within the limbic system affects regulation of emotions, and usually produces indifference and apathy or euphoria.
Basal Ganglia	Middle of the brain	Dysfunction within the basal ganglia causes abnormal movements, and can cause emotional blunting and mental deterioration.
Temporal Lobes, Including Hippocampus	Toward the back surface of the brain	Dysfunction within the temporal lobe impairs the ability to learn and to remember new experiences, and can obliterate old memories.
Parietal Lobe	Toward the back surface of the brain	Dysfunction within the parietal lobe impairs integration and understanding of sensory perceptions, language, and sense of self.
Cerebellum	Lower posterior of the brain	Dysfunction within the cerebellum affects regulation of muscular tone, posture and gait, and coordination, especially of skilled movements.
Hypothalamus	Small area of undersurface of brain above the pituitary gland	Dysfunction within the hypothalamus impairs temperature control, appetite, and hormonal function, including pituitary gland functions.
Pituitary Gland	Base of the brain	Dysfunction of the pituitary gland can impair thyroid, adrenal, and sexual functions, and can affect overall reaction to stress.
Spinal Cord	Begins at base of brain and extends downward through the vertebral column	Dysfunction within the spinal cord affects nerves that spread throughout the body; especially impaired are reflexes and muscle tone.

Footnotes:

1. 5-Hydroxytryptamine or 5-HT.

2. A psychotropic or psychoactive drug is one that affects the brain, mind, and behavior. The term includes nonpsychiatric agents, such as alcohol or marijuana, as well as prescription medications.

3. In the destruction process, serotonin is broken down (degraded or metabolized) into 5-Hydroxyindoleacetic acid (5-HLAA). Measurements of the concentration of 5-HIAA in the brain or spinal fluid are often used as rough indicators of the level of serotonergic nerve activity in the brain.

For more information on the subject the FDA, Prozac and psychiatry get yourself a copy of Talking Back To Prozac by Peter R. Breggin, M.D., the book from which this information was excerpted.

Peter Breggin's Home Site - Peter R. Breggin, M.D. founded The International Center for the Study of Psychiatry and Psychology (ICSPP) as a nonprofit research and educational network concerned with the impact of mental health theory and practices upon individual well-being, personal freedom, and family and community values. For 25 years ICSPP has been informing the professions, media and the public about the potential dangers of drugs, electroshock, psychosurgery, and the biological theories of psychiatry.

What Is Prozac & How It Works Selective Serotonin Reuptake Inhibitors by Peter Breggin, M.D.

Suggested Reading:

What Is Prozac & How It Works
Selective Serotonin Reuptake Inhibitors
by Peter Breggin, M.D.