Prozac and beyond: Journey into the realm of Selective Serotonin
Reuptake Inhibitors
Paul Achuff
Shannon Judy
Michael Sisson
Introduction and History
By, Shannon Judy
Throughout history, depression has been considered solely a
flawed character condition. Even as early as fifty years ago,
there were no pharmaceutical remedies for depression. However,
research in the early 50's brought about theories of a biological
substrate responsible for the onset of depression. Through that
decade and into the 60's, researchers set forth to substantially
improve the known treatments for depression. Two forms of
antidepressants were formulated, tricyclics and MAOIs. However,
there were no major breakthroughs until 1974, when scientists
working in Eli Lilly and Companies laboratories published a study
of fluoxetine hydrochloride (Prozac), introducing selective
serotonin reuptake inhibitors (SSRIs) to the world. However it
was not until 1987 that the FDA approved fluoxetine for treatment
(Mansour, 1994). It was shown to produce less side effects than
the previous antidepressants. Further research produced six
additional SSRIs: Paroxetine, Citalopram, Sertraline,
Amitriptyline, Clomipramine and Fluvoxamine. However, Prozac is
the most commonly prescribed for the treatment of depression
(Tollefson, 1995).
In their search for better antidepressant treatments, the
scientists at Eli Lilly and Company concluded that a
malfunctioning serotonergic system is a cause of major
depression. Their studies revealed lax levels of serotonin at
vital serotonergic receptor locations. This new class of drugs
profoundly changed the ability of serotonin to interact with
those receptors. All SSRIs act in the same manner, by selectively
inhibiting serotonin uptake; however, each varies in selectivity
as well as chemical makeup. The class of selective serotonin
reuptake inhibitors represents an important advance in
pharmacotherapy and has been the catalyst for substantial
serotonin oriented research. Increasing studies indicate that
this drug class has a broad spectrum of potential
indications(Nathan, 1995). The neurochemistry of the serotonergic
system and selective serotonin reuptake inhibitors will be
discussed at greater length in the body of the paper. Moreover,
the primary side effects and behavior changes as well as the
chemical makeup and physiological changes associated with the
administration of Prozac will be revealed.
Neurochemistry of the Serotonergic System and Selective Serotonin
Reuptake Inhibitors
by Paul Achuff
The Serotonergic System
Within the known realm of neurotransmitter substances, serotonin
is perhaps the most implicated in the study and treatment of
various disorders, particularly those of the central nervous
system. Serotonin is an omnipresent neurotransmitter with
extensive projections that provide for the involvement of
serotonin in the regulation of many biological and psychological
functions (Dubovsky and Thomas, 1995). It appears early in brain
development and may play a role in directing the growth of other
neuronal systems (Grahame Smith, 1992). Within the mature brain,
neurons utilizing serotonin have their origin in the dorsal and
median raphe nuclei of the brainstem, with nerve fiber terminals
extending throughout the central nervous system from the cerebral
cortex to the spinal cord (Mollivar, 1987). An indoleamine,
serotonin is widely distributed in both plant, animals, and
humans (Borne, 1994). Although serotonin is found in many edible
sources, its relative large size prevents it from passing through
the blood brain barrier (Tollefson, 1995). Serotonin, therefor,
is synthesized from within certain brain cells in two steps, from
the naturally occurring amino acid tryptophan (Thompson, 1985).
Blood capillaries carry tryptophan towards a neuron, where it is
then actively transported into that neuron. Upon entry, it
travels down to the terminal button where catalyzation begins. It
is first acted upon by the enzyme tryptophan hydroxylase,
creating 5hydroxytryptophan (5 HTP). It is then further catalyzed
by another enzyme, 5HTP decarboxylase, which results in the
production of serotonin, 5hydroxytryptamine (5HT). Newly formed
serotonin is then stored with other serotonin neurotransmitters
within a vesicle (Marsden, 1991). Serotonin remains inside the
vesicle until an electrically charged impulse is sent down
through the neuron to the terminal button. This action potential
causes calcium channels to open, resulting in a neuronal influx
of calcium ions. This overabundance of calcium within the
terminal button causes vesicles to burst, releasing serotonin
neurotransmitters into the synaptic gap (Carlson, 1998). Once
within the synaptic gap, the serotonin neurotransmitters interact
with postsynaptic and/or presynaptic serotonin receptors
distributed throughout the central nervous system. After initial
binding with receptors, the receptors reverse polarization,
releasing the serotonin neurotransmitters back into the synaptic
gap. Once again within the gap, they can be terminated either
through metabolization by 5hydroxyindoleacetic acid within the
cerebrospinal fluid, or diffused; however, serotonin is generally
inactivated by uptake through a sodium/potassium adenosine
triphosphatase dependent carrier into nerve terminals, and
restored within vesicles (Shaskan and Snyder, 1970).
Serotonin receptors were originally only divided into two
subtypes, 5HT1 and 5HT2 (Peroutka and Snyder, 1979). However, due
to technological advances, there is now solid evidence of the
presence of fourteen serotonin receptors: 5HT1a,b,d,e,f,
5HT2a,b,c, 5HT3, 5HT4, 5HT5a,b, 5HT6, and 5HT7 (Mansour et al.,
1995). Differences in the serotonin receptors location and
function allows for serotonin to participate in the regulation of
multiple functions, with different receptors some times
participating in the regulation of the same function (Walker,
1985).
While the initial release of serotonin is initiated by an
increase in intracellular calcium levels, long term release is
dependent upon autoreceptors (deMontigny and Aghajanian, 1977).
Autoreceptors are specific receptors found on neurotransmitter
producing cell bodies or presynaptic terminals, which upon
stimulation, inhibit further transmitter release (Carlson, 1998).
There are thought to be seven serotonin receptors located
presynaptically: 5HT1a,b,d,f, 5HT2c, 5HT3, and 5HT7 (Mansour et
al., 1995). Each is located postsynaptically as well. The
physiological action of selective serotonin reuptake inhibitors
(SSRIs) may possibly be delayed by autoinhibition at the cell
bodies of the raphe neurons, Therefor, by blocking these
autoreceptors, the onset of antidepressant action should not be
delayed (Goodwin, 1996). The 5HT1a autoreceptor antagonist
pinodol, has been reported to accelerate the antidepressant
response to SSRIs, theoretically doing so by preventing an
initial decrease in firing activity of serotonin neurons (Blier
et al., 1997).
Although great interest surrounds serotonin as a
neurotransmitter, since most clinical studies have been carried
out in the neural cells of invertebrates, rather little is known
of its influence on mammalian cell membranes (Gershenfeld and
Stefani, 1966). The rate of neuronal discharge after
intraarterial, intraventricular or microelectrophoretic injection
of serotonin in the vicinity of serotonergic neurons has been
taken to indicate an inhibitory or facilitatory effect. In
mammals, the predominant effect on neuronal function seems to be
inhibitory. However, a facilitatory effect has also been found in
many parts of the central nervous system (Nikitopoulou Maratou et
al., 1981).
Selective Serotonin Reuptake Inhibitors
Research of the serotonergic system began in 1960's Europe, with
the hypothesis that serotonergic inadequacies produced depressive
symptoms (Coppen, 1968). This theory was then furthered by Asberg
(1976a), who concluded that depressed patients with low
cerebrospinal fluid concentrations of 5hydroxyindoleacetic acid,
a serotonin metabolite, were at great risk for committing
suicide. Current research directly correlates central serotonin
abnormalities with disturbances in mood, satiety, anxiety,
cognition, aggression, and sexual drive (Tollefson, 1995).
Depression is an affective disorder, the origins of which can
not be explained by any one cause. However, the most widely
endorsed hypothesis implicates an abnormal functioning
catecholamine and/or serotonin transmitter system. This theory
regards depression as a deficiency of norepinephrine and/or
serotonin at functionally important adrenergic or serotonergic
receptors (Borne, 1994). Therefor, theoretically, if a depression
is alone caused by serotonin deficiency, multiplying the initial
release of serotonin into the synaptic gap and/or increasing its
time within the gap, should prevent depression. SSRIs act by
blocking the reuptake pump used by the neurons to recycle
previously released neurotransmitters. As a direct result,
serotonergic neurotransmissions are acutely intensified by
allowing serotonin to act for an extended time at synaptic
binding sites. In this manner, SSRIs exhibit action similar to
those seen in direct acting agonists. However, unlike direct
acting agonists, SSRIs depend on neuronal release of serotonin
for their action (Mansour et al., 1995).
While all SSRIs act in the same manner, each varies in
selectivity. The widely held notion that SSRIs are selective
clinically and biochemically has important shortcomings (Dubovsky
and Thomas, 1995). The most potent inhibitor of serotonin uptake,
paroxetine, is also a relatively potent inhibitor of
norepinephrine uptake (Bolden Watson and Richelson, 1993).
Furthermore, SSRIs have been found to interact with alpha and
beta adrenergic, benzodiazepine, and possibly dopamine D1
receptors, and fluoxetine has an affinity for histamine, D2 and
5HT1c and 5HT1d receptors (Levy and Van De Kar, 1993)
The actions of SSRIs have been implicated in more than the mere
inhibition of serotonin uptake. They are thought to be
characterized by a reduced sensitivity of 5HT1a/b sites; both
display a high affinity for serotonin (Sleight et al., 1988). The
5HT1a receptor in particular has been implicated in the
pathophysiology of depression (Nathan et al., 1995). Studies also
suggest an increased quantity of postsynaptic 5HT2 receptors in
the brain of depressed patients. 5HT2 receptors functionally
inhibit postsynaptic propagation of a nerve impulse. The
increased upregulation of 5HT2 binding sites has been implicated
in major depression (Pandey et al., 1990). Although rather
inconclusive, 5HT2 behavioral models demonstrate that potention
lessens after repeated SSRI exposure consistent with 5HT2
receptor adaptation (Marshall et al., 1988). Downregulated or
reduced density of 5HT2 binding sites in rat frontal cortex is
correlated with chronic administration of many modern
antidepressants (Peroutka and Snyder, 1980). These adaptive
variations are thought to be essential for an antidepressant
response. However, since several SSRIs are absent of such
activity, it is unknown how essential the effect really is
(Cowen, 1991).
These factors are not necessarily exclusionary. It is quite
possible that 5HT1a and 5HT2 binding sites could interact. 5HT2
antagonists attenuate a 5HT1a agonists,
8hydroxydipropylaminotetralin, ability to release serotonin
(Backus et al., 1990). SSRIs, as a drug class, have been reported
to normalize both 5HT1a and 5HT2 receptor density among depressed
patients (Leonard, 1992).
Studies of fluoxetine (Blier et al., 1998), citalopram (Chaput
et al., 1986), paroxetine (deMontigny et al., 1989), fluvoxamine
(Dresse and Scuvee Moreau, 1984), and sertraline (Heyn and Koe,
1988) have revealed that SSRIs transiently inhibit dorsal raphe
firing, decrease terminal autoreceptor function, and ultimately
increase net serotonin synaptic transmission within CA3 pyramidal
cells in the hippocampus. Electrophysiologic studies suggest that
most antidepressants enhance net serotonin after chronic
administration. SSRIs accomplish this by reducing sensitivity
among somatodendritic and terminal autoreceptors (Blier et al.,
1990).
Although SSRIs have proven effective in alleviating the symptoms
associated with depression, clinical improvement is seen only
after several weeks of treatment (Tollefson, 1995). This aspect
is attributed to the likely existence of different regulatory
mechanisms directly controlling serotonergic transmissions. While
the release of serotonin from terminal buttons is regulated by
autoreceptors, the firing rate of dorsal raphe serotonergic
neurons falls under the control of somatodendritic 5HT1a
autoreceptors. Moreover, the rate limiting enzyme involved in the
synthesis of serotonin, tryptophan hydroxylase, is controlled by
5HT1a and possibly 5HT1b/d receptors. Following chronic
administration of SSRIs, these regulatory mechanisms become
desensitized; consequently, serotonergic neurotransmissions are
weakened or lost. This effect causes serotonin levels to increase
within the synaptic gap, facilitating stimulation of postsynaptic
receptors. Thus, only after repeated administration can the
activity of SSRIs be completely expressed in terms of synaptic
serotonin levels. This hypothesis may explain the delay of
antidepressant action seen with some patients (Briley and Moret,
1993).
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Primary Side effects and Behavior Changes
by Shannon Judy
Prozac (Fluoxetine Hydrochloride) is greatly effective for
major depression. It also has been used to treat OCD (Obsessive
Compulsive Disorder), panic disorder (attacks), and bulimia
nervosa. There are different side effects for each disorder
treated with Fluoxetine. The dosage of Fluoxetine and the
treatment depend on the indications and usage.
Fluoxetine is usually begun at a dosage of 20 mg/day given
in a single daily dose. It is generally given in a single daily
dose. It is generally given in the morning because for many
patients it has a stimulatory effect; doses greater than 20
mg/day may be divided, with the second dose given during the
afternoon. Although an antidepressant effect is usually apparent
within 2-4 weeks, improvement may continue over 2 months. A
major advantage of fluoxetine and other SSRIs, is that these
newer drugs are far less dangerous than cyclic antidepressants or
MAOIs when taken in overdose (Hyman, Arana, & Rosenbaum, 1995).
Prozac can help to fight depression. According to Eli
Lilly USA (1997), some people experience mild side effects, like
upset stomach, headaches, difficulty sleeping, drowsiness,
anxiety and nervousness. These tend to go away within a few
weeks of starting treatment and usually aren't serious enough to
make most people stop taking it. However, if you are concerned
about a side effect, or if you develop a rash, tell your doctor
right away. And don't forget to tell your doctor about any other
medicines you are taking. Some people should not take Prozac,
especially people on MAO inhibitors (Lilly, 1997).
Fluoxetine has a distinctive side - effect characteristic of
many of the new generation of serotonergic antidepressants.
Minimally sedating (and possibly even "activating" for some
patients), fluoxetine produces few anticholinergic effects. It
can be associated with gastric irritation (nausea, heartburn)
unwanted CNS irritability (anxiety, agitation or insomnia) and
headache. Impressively, at usually therapeutic doses fluoxetine
appears well tolerated by many patients (Gelenberg, Bassuk, &
Schoonover, 1995).
The most problematic side effects of fluoxetine include
agitation, neuromuscular restlessness (which may approximate
neuroleptic induced akathisia), and insomnia. A minority of
patients may develop daytime sedation from fluoxetine. Sexual
dysfunction may occur in both males and females, most frequently
delayed ejaculation or anorgasmia, which may lead to drug
discontinuation by some patients. Unlike cyclic antidepressants,
fluoxetine does not appear to cause weight gain; some patients,
especially those on higher doses, may lose weight. Fluoxetine
may precipitate mania in bipolar patients. Other side effects
include nausea, headache and diarrhea (Hyman et al., 1995).
There has been reports of serious, sometimes fatal,
reactions (including hyperthermia, rigidity, myoclonus, autonomic
instability with possible rapid fluctuations of vital signs, and
mental status changes that include extreme agitation progressing
to delirium and coma) in patients receiving fluoxetine in
combination with a monoamine oxidase inhibitor (MAOI), and
in patients who have recently discontinued fluoxetine and are
then started on an MAOI. Prozac should not be used in
combination with an MAOI (Lilly, 1997). A warning put out by Eli
Lilly and company distributer of Fluoxetine Hydrochloride, states
that "In US fluoxetine clinical trials, 7% of 10,782 patients
developed various types of rashes and/or urticaria. Among the
cases of rash and/or urticaria reported in premarketing clinical
trials, almost a third were withdrawn from treatment because of
the rash and/or systemic signs or symptoms associated with the
rash. Clinical findings reported in association with rash
include fever, leukocytosis, arthralgias, edema, carpal tunnel
syndrome, respiratory distress, lymphadenopathy, proteinuria, and
mild transaminase elevation" (Lilly, 1997).
Prozac, out of all the SSRI's is the best studied in the
treatment of bulimia. Antidepressants produce improvement in
binge frequency, vomiting and other purging, and attitude toward
eating. In a multicenter placebo-controlled, double-blind trial
of fluoxetine for bulimia, a dose of 60 mg/day was superior to 20
mg/day, which was in turn superior to placebo. These data and
clinical experience suggest that higher doses of SSRIs than are
typically used for depression may be required to treat bulimia
(Hyman et al., 1995).
References
Gelenberg, A. J., Bassuk, E. L., & Schoonover, S. C. (1995).
The Practitioner's guide to Psychoactive Drugs.
Hyman, S. E., Arana, G. W., & Rosenbaum, J. F. (1995). Hand
book of Psychiatric Drug Therapy.
Lilly, E. & Co. (1998). Prozac. Internet side effects and
behaviors of Prozac {online}.
Prozac: Chemistry, Route of Access, Physiological Changes, and
Alternate Approach.
by Michael Sisson
My paper will deal with the chemistry of Prozac,
(Fluoxetine Hydrochloride) the route of access, and physiological
or whole body changes. During the conclusion, I will also
discuss an alternate way to increase serotonin synaptic gap
levels.
Prozac or Fluoxetine Hydrochloride is an antidepressant for
oral administration. It is chemically unrelated to tricyclic or
tetracyclic antidepressant agents. It is designated N methyl 3
phenyl 3 propylamine hydrochoride and has the empirical formula
of C17 H18 F3 NO HCL. Its molecular weight is 345.79 (Lilly,
1998). The presence of the p trifluoromethyl substituent on the
molecule appears to contribute to the drug's high selectivity and
potency for inhibiting serotonin reuptake. Fluoxetine is
commercially available as a hydrochloride salt (McEvoy, 1998).
At least 60 to 80% of Prozac appears to be absorbed from
the GI tract after oral administration. Food appears to slow the
rate but not the final extent of absorption. Peak Plasma
Fluoxetine concentrations usually occur within 4 to 8 hours.
This contrasts with EEG and behavioral changes which generally
take 8 to 10 hours after single doses. (Full therapeutic effect
may take up to 4 weeks). The difference is thought to relate to
formation of an active metabolite or delayed distribution to the
central nervous system (McEvoy, 1998). Approximately 94.5% of
the absorbed drug is bound invitro to human serum proteins
including albumin and a1 glycoprotein. Because of this, Prozac
and interaction of other highly protein bound drugs may cause a
shift in plasma concentrations potentially resulting in an
adverse affect. Fluoxetine (Prozac) is metabolized in the liver
to norfluoxetine and other metabolites. (Lilly, 1998)
Norfluoxetine is formed by N demethylation of fluoxetine which
may be under polygenic control. Long term administration to
animals indicated norfluoxetine was widely distributed in body
tissues with the highest concentration in the lungs and the
liver. The drug crosses the blood brain barrier in humans and
animals. In animals, norfluoxetine ratios were similar in the
cerebral cortex, corpus striatum, hippocampus, hypothalamus,
brain stem, and cerebellum. Fluoxetine and norfluoxetine were
found to cross the placenta in rats following oral
administration. The drug and metabolite concentrations in human
milk were about 20 to 30% of concurrent plasma concentrations.
(McEvoy, 1998) Fluoxetine and norfluoxetine are eliminated
slowly. Norfluoxetine has a half life averaging 7 to 9 days.
The drug and principal metabolite may be in the system for 35
days after discontinuance (or longer depending on the
individual). Liver disease (the primary site of metabolism is the
liver) can slow the elimination even longer. (Lilly, 1998)
Physiological changes (like side effects) are numerous but
less of a problem than of previous generations of
antidepressants. It would be impossible in a brief paper to list
them all but a review is in order. Refer to the sited reference
for more complete information. In particular, the book edited by
McEvoy is excellent. These effects must also be counterbalanced
by the estimate that 7 to 15% of severely depressed people commit
suicide. (Comer, 1998). Frequent observable events during U.S.
clinical trials are defined as occurring on 1 or more occasions
in at least 1 of 100 patients ; infrequent adverse events are
defined as those occurring in 1 of 100 to 1 of 1000 patients.
Rare effects are those occurring in less than 1 in 1000 patients.
The most frequent physiological event was chills. Chills and
fever together was an infrequent event. In the cardiovascular
system, hemorrhage and hypertension are listed as a frequent
event. (One or more occurrences in at least 1 of 100 patients)
(Lilly, 1998) A causal relationship to the drug has not been
established though. However in serotonin syndrome, which is
uncommon and usually "mild", serious complications such as
seizure, respiratory failure, severe hyperthermia, disseminated
intra vascular (heart) coagulation, and death have been reported.
The precise mechanism is unknown but appears to result from
excessive serotonergic activity in the central nervous system,
probably caused by activation of 5HT1A receptors or possibly the
involvement of dopamine (a different neurotransmitter) and 5HT2
receptors. The syndrome most commonly occurs when 2 or more
serotonin agents with different mechanisms of action are
administered either concurrently or in close succession. (Prozac
has been the selective serotonin reuptake inhibitor (SSRI) most
commonly implicated because of the long half life. Its
recommended that 5 weeks elapse before discontinuance of Prozac
and initiation of MAOI's, for example). MAOI's (monoamine oxidase
inhibitor) which decreases the metabolism or destruction of
serotonin seem to be responsible for most of the cases of
serotonin syndrome. However MDMA (street name "ecstasy") or
methylenedioxy methamphetamine and other substances have also
been implicated in certain circumstances (McEvoy, 1998). A more
common physiological effect is excessive sweating which occurs in
8% of the patients. Blurred vision occurs in 3% and back,
joint, and limb pain in 1 to 2%. Although less than 1% of Prozac
patients had weight gain, another 13% had weight loss. An
interesting effect Prozac has is suppression of rapid eye
movement (REM). Unlike previous generation antidepressants like
tricylics which usually increase slow wave sleep, fluoxetine
reduces REM sleep by increasing the time to onset of REM sleep
and by decreasing the number rather than the duration of REM
episodes. (McEvoy, 1998) Does this mean that fluoxetine is
responsible for less events needing to be resolved in REM dream
sleep?
With all the side effects of Prozac (report by Shannon
Judy) and the intricacies of the pre and post synaptic serotonin
receptors, (report by Paul Achuff) the operation of many of which
is unknown or guessed at, the question remains whether another
safer way to increase serotonin in the synaptic gap might exist?
Actually tryptophan, the amino acid eventually transformed into
serotonin (report by Paul Achuff) was available in supplement
forms until banned by the FDA in Nov. 1990 due to a disease
outbreak. Subsequently it was discovered the illness was due to
a contaminated batch. Ironically, tryptophan is still safe
enough to be approved by the FDA to be available in the U.S. in
infant formulas and parenteral (IV feedings) solutions. (Smart
Basics Inc. , 1997) (Note: the best food sources of Tryptophan
are pineapple, turkey, chicken, yogurt, bananas, and unripened
cheese. (Smart BASICS Glossaries Tryptophan, 1997)) Tryptophan
is also available in Canadian pharmacies while 5HTP or
5hydroxtryptophan (the intermediate step between tryptophan and
5HT or serotonin) is available in European pharmacies and now in
America as a supplement in vitamin stores. (Baumel, 1997). 5HPT,
as an intermediate metabolite, besides being converted into
serotonin is also converted into melatonin, a neurohormonal
associated with sleep. (Smart Basics Inc. , 1997). ( In 1994 Utah
Sen. Orrin Hatch pushed through legislation exempting natural
supplements from the FDA oversight that drugs face. This means
that there is no governmental regulation over the manufacture of
supplements or even of the promoting that they work. (ABC 1998)).
Tryptophan itself is postulated as a potential treatment for
Tourette's Syndrome. A recent study by the National Institute of
Mental Health has localized one aspect of Tourette's syndrome to
the caudate nucleus, a region of the brain that is closely
associated with control of voluntary movements and obsessive and
compulsive behaviors. (Recall that Prozac is used in treatment of
obsessive and compulsive behavior.) (Fowkes, 1997) Another study
of drug free adults with autistic disorder showed that short term
tryptophan depletion (plasma totaled 86% depletion) led to a
significant increase in behaviors such as whirling, flapping,
pacing, banging and hitting self, rocking, and toe walking. This
is consistent with previous research that implicates a
dysregulation of serotonin in some patients with autism.
(thriveonline.com, 1997) Possibly use of SSRIs (like Prozac) in
some cases then might also help. Richard Wurtman of MIT has
found that high carbohydrate, low protein meals affect levels of
serotonin, a clear indication that dietary changes may be an
effective means of altering brain chemistry. Wurtman says, "The
chemistry of your brain depends very much on what you ate for
breakfast." (Crime Times, 1995) (Assuming, of course, you had
breakfast). (Vitamin C and B vitamins support the conversion of
tryptophan through the process to serotonin. Vitamin B6 is said
to be critical to the conversion).
So why take Prozac if tryptophan and 5HTP dietary
supplements could do the job? Well, a choice has to be made.
Tryptophan is mostly banned in the U.S. 5HTP is unregulated by
the FDA. Of course both, as essentially amino acids, can't be
copyrighted by some huge feudal like corporation as Prozac is, so
they won't be advertised the same, either. Certainly tryptophan
and 5HTP can increase the production of serotonin for use in the
synaptic gaps of the central nervous system for most people.
Concurrent use of tryptophan and Prozac resulted in some adverse
effects that resemble the milder forms of serotonin syndrome
(agitation, insomnia, headaches, nausea, diarrhea, etc.) These
symptoms were resolved within several weeks of discontinuance of
the tryptophan. (McEvoy, 1998) Presumably this could occur with
5HTP also. When Prozac blocks the reuptake and more serotonin
(5HT) is being produced (by the increased availability of
tryptophan or 5HTP), too much serotonin is presumably in the gap
in these cases. If one could "get away" with just taking 5HTP to
lower depressive symptoms, though, one would not have to worry
about any other possible known or unknown effects Prozac might be
having on different presynaptic or post synaptic receptors or
autoreceptors.
References
Lilly, E. and Co. (1998) PROZAC [ONLINE]
McEvoy, G. K. (Ed.) (1998) American Hospital Formulating Service,
American Society of Health System Pharmacists, Inc.
Corner, Ronald J. (1998) Abnormal Psychology New York: W.H.
Freeman and Company
Baumel S. (1997) Tryptophan and 5HPT[ONLINE] Available:
http://www.escape.CA~sgh/ems.html
Smartbasics Inc (1997) 5Hydroxy Ltryptophan [ONLINE] Available:
http://www.smartbasic.com/glos.news/1.5htp.html
Smartbasics Inc (1997) Glossaries Tryptophan [ONLINE] Available:
http://www.smartbasic.com/glos.aminos/tryptophan.glos.html
ABCNEWS (1998) Help or Hype? Can one pill cure depression,
obesity and insomnia? [ONLINE]Available: http://www.netrition.com
Fawkes, S.W. 1997 Tryptophan and Tourettes Syndrome [ONLINE]
Available: hhtp://www.ceri.com/tourett.html
Thriveonline.com (1997) Effects of tryptophan depletion in drug
free adults with autistic disorder [ONLINE] Available:
hhtp://www.thriveonline.com/health/Library/CAD/abstract25679.html
Crime Times (1995) A treatable Problem [ONLINE] Available:
http://www.crime times.org/95a/w95ap11.html
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Copyright © 1995, Dr. John M. Morgan, All rights reserved -
This page last edited October 7, 1998
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