Prozac
By John Salguero
Serotonin is a neurotransmitter (one of many in the human body); neurotransmitters are ligands which diffuse across the synaptic cleft of neurons and bind to receptors in the postsynaptic membranes of other neurons. Receptors for serotonin are found throughout the brain and spinal cord. Serotonin itself is involved with sleep function, mood, anxiety, aggression, and depression. It also helps form scabs, is involved with the inflammation process and blood vessel dilation (and constriction), and affects digestion. What Prozac does chemically is block the reabsorption of serotonin, increasing and prolonging the free-floating concentrations of it in the brain.
There are other older forms of anti-depressants knowns as MAOIs, or Monamine Oxidase Inhibitors, which react badly with SSRIs and to understand why you need to know how SSRIs actually function.
It has been known for many years that patients with severe clinical depression had low levels of serotonin in their brain, but it is only since 1954 that there has been significant research into the biochemical causes of depression. Studies have shown that the levels of cortisol and serotonin in the blood are balanced like an alchemist’s scale—when one goes up the other goes down— and that it is actually elevated levels of cortisol in the brain which are involved with depression. It is much easier to add into a complex system than to subtract; by blocking reabsorption and increasing the levels of serotonin in the brain, Prozac indirectly reduces the cortisol level in the brain and helps reduce depressive effects.
MAOIs, on the other hand, blocked the production of monoamine oxidase, the enzyme that chemically breaks down serotonin. However, MAO is not specific to serotonin and also breaks down the family of catecholamine (or monoamine) neurotransmitters such as dopamine (involved with voluntary muscle control), norepinephrine, and epinephrine as well as serotonin. Consequently the MAOIs tend to have a wide range of persistent side effects associated with elevating the levels of all these neurotransmitters. Prozac blocks only serotonin and is much more specific as a treatment for depression.
The active ingredient in Prozac is generally called fluoxetine hydrocholoride (short name); chemically it is called N-methyl-3-phenyl-[(a,a,a-trifluoro-p-tolyl)oxyl]propylamine hydrochloride and has a molecular weight of 345.79.
On the molecular level, Prozac is a racemic mix (50/50) of enantiomeric fluoxetine hydrochloride molecules— R and S (rectus and sinistrus, or right and left). Although both molecules are specific SSRIs, S-fluoxetine hyrochloride is metabolized much more slowly and consequently is present in a larger concentration in the blood. No one seems to know why this is so, but studies in animals have shown that R-fluoxetine is less effective as a SSRI.
Prozac is chemically synthesized and there are no precurser molecules that it is naturally present in.
About 7% of the population carries a gene which reduces the level of a metabolizing isoenzyme CYP2D6 (cytochrome P450 isoenzyme 2D6); these “poor metabolizers” are at a higher risk for side effects from using Prozac and require a much smaller dosage to be effective. Currently a DNA test is being developed to test for this characteristic. Those people who are poor metabolizers show side effects associated with overdosages; additionally there are other side effects caused by interactions with other drugs that artificially affect metabolizing enzymes (for Prozac, and for other substances). Therefore Prozac should also not be taken by those currently taking CYP2D6 (cytochrome P450 isoenzyme 2D6) inhibitors such as flecainide, vinblastine, and various tricylics or with thioridazine.
The chemical pathways of depression are not well understood and is hypothesized that are as many as one hundred separate genes that are responsible for various biochemical imbalances that bring about clinical depression. Given the wide range of possible chemical pathway disturbances that cause depression, it is not surprising to find that Prozac does not work in all patients. Approximately 50% of patients initially prescribed Prozac do not respond well to it or have reduced response. For those patients there are other less effective or more dangerous drugs or therapies. For those that Prozac is effective, there can be any number of various side effects.
Typical side effects are present in at least 5% of patients studied and include a whole laundry list of various effects affecting different systems. Side effects have been noted in the following: cardiovascular, digestive, nervous, respiratory, integumentary, and urogenital systems. Types of side effects vary widely but the most common is decreased sexual desire; strangely enough, in men this is often accompanied with priapism. Digestive disorders are also common and include nausea, diarrhea, constipation, dry mouth, and loss of appetite. Many people lose weight on Prozac, but Prozac should in no way be considered a weight loss drug. An extremely small percentage of patients report problems with vision and focusing.
There has also been a number of well-publicized cases where patients taking Prozac “went postal” and committed murder-suicides. Increased aggression can be a side effect of Prozac but Lilly attributes these cases to poor diagnosis and follow up by psychiatrists prescribing the drug. Lilly’s stance on product liability is that as the second-most widely prescribed drug in the US Prozac is more likely to wrongly prescribed and more likely to be blamed in cases of unknown pre-existing psychoses.
There is increasing evidence in fact, that Prozac is not only poorly prescribed, but overly prescribed in the United States. It could be that there is that much more chance of abuse because Prozac is one of the most effective drugs for the treatment of depression. However, Prozac accounted for $2.61 billion in sales in 1999 (about $2 billion of which was in the United States) which is 25% of Eli Lilly’s total sales— it is quite possible that Prozac is abused because Lilly’s marketing has been so effective in convincing everyone that it a cure-all for all mental illnesses (which it is most assuredly not).
Overdoses of Prozac usually result in vomiting and seizures. In rare cases overdoses have lead to cardiac arrythmia and death. The lowest fatal overdose was 520mg (26 capsules) and the highest non-fatal dosage was 8000 mg (400 capsules).
Prozac is usually taken orally as a 20mg capsule and is prescribed in doses of 20mg to 60mg maximum daily depending on symptoms. It is also available as 10mg capsule, a 40mg capsule, and a 10mg tablet.
It can also be taken in an oral solution of 20mg/5 mL and in a time-released 90mg capsule called Prozac Weekly. None of these forms are controlled substances and thus are available for mail order with a prescription all over the world.
At the suggested retail price and with a prescribed dosage of 20mg daily, Prozac costs around $2.63 per day.
Reference reading
The Noonday Demon by Andrew Solomon, 2001,
569 pp., Touchstone Books (Simon and Schuster), New York, NY; $16.00. Definitive
history and overview of clinical depression told from a first-hand viewpoint.
Winner of the 2001 National Book Award for Non-Fiction and finalist for
Pulitzer Prize.
Anatomy and Physiology by Seeley, Stephen, Tate; 2000, 1106 pp., McGraw Hill, New York, NY. Textbook.
Listening to Prozac by Peter Kramer M.D., 1993,
409 pp., Penguin, New York, NY, $12.95. Thorough review of the effects
of taking antidepressants (like Prozac).
Prozac’s medical legacy will outlast its patent by Shankar Vedantam, August 05, 2001; Seattle Times, Seattle, WA. News article from health section.
Generic Prozac arrives as Eli Lilly patent runs out by Theresa Agovino, August 03, 2001; Seattle Times, Seattle, WA. News article from health section.
Vehicular Suicides: Eleven Case Studies by
Alex Pokorny, M.D. et. al; pps. 83-91 of Car Crash Culture,
ed. Mikita Brottman, 2001, Palgrave, New York, NY; $19.95. Chapter from
a cultural history speculating that many car crashes classified as accidents
are really suicides by depressed people.
Prozac Public Information Release by Eli Lilly Company, July 29, 2002; 24 pp.; www.prozac.com, Indianapolis, IN.
Biography of David Wong, inventor of Prozac; www.cccu.org/chem/profileID.10/profile.asp
Side effects reported from recent Prozac use, statistical data from FDA; www.oism.info/ospiti/prozac/01-001.htm
Article on new book about Prozac abuse; abcnews.go.com/sections/living/DailyNews/prozacbacklash000407.html