Do You Have Serotonin Deficiency Syndrome?

[Guest guest]

Do You Have " Serotonin Deficiency Syndrome? " Depression, anxiety, insomnia,

overeating, PMS, migraine, OCD, aggressive or violent tendencies, fibromyalgia,

alcoholism, and bulimia are all associated with relatively low levels of

serotonin. At the same time, treatments like tryptophan, 5-HTP, and the SSRIs,

which increase serotonin levels in the synapse, can alleviate all these

disorders. These two facts have caused some researchers, led by Dr. Walter

Pöldinger, of the Psychiatrische Universitätsklinik, in Basel, Switzerland, to

conclude that these disorders may each represent a different manifestation of

the same underlying disorder, which they call " serotonin deficiency syndrome. "

In other words, when you feel depressed, anxious, etc, you may not be suffering

from " depression " or " anxiety " per se, but rather from a generalized reduction

in serotonin activity. Depending on your individual physiology, you may

experience this as depression, anxiety, or other symptoms. Pöldinger suggests

that this syndrome can best be treated by restoring normal serotonin levels,

preferably using 5-HTP.10 5-HTP: The Natural AntidepressantThe scientific

realization that depression is often the psychological/emotional manifestation

of a biochemical imbalance has revolutionized the way we view and treat this

disorder. Not only does it remove much of the stigma traditionally attached to

depression -- " It's not me, it's my serotonin! " -- it has also spurred the

development of treatments, from natural amino acids to high-tech pharmaceuticals

to bright lights, that now allow many people with serious depression to lead

normal lives. The idea that serotonin was a crucial neurotransmitter in

depression was first proposed in the mid-1970s.15 This conclusion was based

partly on the observation that many people with depression had low levels of a

metabolite of serotonin -- 5-hydroxyindoleacetic acid (5-HIAA) -- in the fluid

that surrounds their brain and spinal cord. Low 5-HIAA suggests that the

brain is not producing -- and therefore not metabolizing -- a normal amount of

serotonin.Researchers also discovered that people who had attempted suicide had

abnormally low levels of 5-HIAA in their brains. This finding suggested that a

serotonin deficiency may actually predispose some people to kill

themselves.16-18 If low serotonin causes all these negative effects, does

restoring this deficit bring you back to " normal? " The overwhelming weight of

the evidence suggests that it does. As we discussed in the previous chapter,

there are two basic ways to normalize serotonergic functioning in the brain in

someone with a serotonin deficiency: Increase the amount of serotonin nerve

cells produce. This is how tryptophan and 5-HTP work.Slow down the degradation

of serotonin already produced. This is how Prozac and virtually all other

antidepressant pharmaceutical agents work. Even St. John's wort is thought to

relieve depression, at least partly, by blocking serotonin reuptake.

Accumulating EvidenceThe evidence that 5-HTP can reduce depression has been

accumulating for three decades.* In preliminary studies dating back to the late

1960s and early 1970s, 5-HTP given to seriously depressed people was reported to

produce dramatic and sudden improvements.19-21 In a 1975 study from Japan,22 24

adults hospitalized with severe depression took 300 mg of 5-HTP daily for up to

2 weeks. At the conclusion of the study, seven individuals were showing " marked "

improvement, and two were showing " mild " improvement. Moreover, those who

responded did so quite rapidly -- in 3 to 7 days -- and continued to experience

antidepressive effects for several weeks after they stopped taking the 5-HTP. *

(This clinical literature is largely unknown amoung US physicians, because most

of it has been carried out in Europe or Japan, and much of it, especially the

early studies, was not published in English language journals.)Although

improvement by about one-third of the patients may not

seem all that impressive on its face, we need to consider three important

qualifications of these results: first, the patients were all severely

depressed, thus stacking the deck against any potential treatment. Second, even

the best antidepressants generally have only about a 60 to 80% response rate.

Third, this was a test of a single dose for a fixed -- and relatively short --

period of time. It is possible that some people may require higher doses and

treatment for longer periods of time. It is typical for people taking SSRIs and

other antidepressant drugs to require at least 2 to 3 weeks before feeling their

full effect. The fact that nine patients taking 5-HTP showed noticeable

improvement within only 3 to 7 days is actually quite remarkable. Various other

small studies compared 5-HTP with placebo or other active substances thought to

have antidepressant activity (eg, tryptophan, imipramine, l-deprenyl). In a

review of all the early clinical studies, one author concluded that

5-HTP has definite antidepressant properties that are comparable to other

available drugs (the SSRIs were not yet available) and was associated with fewer

adverse effects.23Since many of these early studies included relatively few

subjects or lacked some important controls, it is impossible to draw firm

conclusions from them. Thus, these results should be considered suggestive, but

far from conclusive. A more recent, well-controlled, comparative study puts

5-HTP treatment for depression on far firmer footing, showing it to be equal to

or better than a state-of-the-art SSRI. The Key Comparative StudyThis important

study -- a head-to-head comparison of 5-HTP and the SSRI drug Luvox7

(fluvoxamine) -- was conducted by a team of researchers headed by Dr. Walter

Pöldinger of the Psychiatrische Universitätsklinik, Bern, Switzerland, and the

results were published in 1991.10 The investigators gave 69 depressed patients

either 5-HTP or fluvoxamine; treatment lasted 6 weeks. The researchers

employed a double-blind design, so that neither the patients nor the

researchers knew which treatment a given patient was getting until the study was

over. The patients' degree of depression was assessed objectively using standard

depression rating scales (Hamilton Rating Scale for Depression, HRSD), as well

as the more subjective global impressions of investigators and the patients

themselves. As shown in Figure 3, both the 5-HTP- and the fluvoxamine-treated

patients showed a highly statistically significant reduction in depression

scores that gradually increased at 2, 4, and 6 weeks. By week 6, 22/34 (65%)

5-HTP-treated patients had improved by more than 50%, compared with 21/29 (72%)

of the patients in the fluvoxamine group, but this difference was not

statistically significant. Overall, there was virtually no difference between

the two groups in terms of antidepressive effect, although a closer examination

of the data suggested a slight advantage for 5-HTP. The patients= and

investigators= evaluations of the degree of depression generally paralleled

those of the objective tests. There were more treatment failures in the

fluvoxamine group than in the 5-HTP group (17.2% vs 5.9%), but again, this

difference was not statistically significant.For both groups, the most common

adverse effects encountered were gastrointestinal in nature, including nausea,

heartburn, stomach discomfort, constipation, and reduced appetite. Most of these

occurred within the first few days of treatment. Although the two treatments

differed little in terms of relative tolerance or safety, 5-HTP again appeared

to come out looking slightly better. Fourteen patients in the 5-HTP group (39%)

reported a total of 43 adverse events, compared with 18 patients (54%) in the

fluvoxamine group, who reported a total of 50 adverse events (Fig. 4). For four

of these fluvoxamine patients, the adverse effects were so bad they had to drop

out of the study. Only one 5-HTP patient dropped out. While

none of these differences was statistically significant, one difference was

highly significant. The adverse effects associated with 5-HTP were significantly

milder (Fig. 5).To sum up the two major results of this important clinical

trial:5-HTP and fluvoxamine were equally effective in relieving depression.5-HTP

was superior to fluvoxamine in terms of tolerance and safety, because 5-HTP was

associated with fewer adverse side effects that were also significantly less

severe, compared with those caused by the SSRI.Patentability and PromotionIf

5-HTP is such a good antidepressant, why have most physicians never heard of it,

while the use of SSRIs continues to explode? Dr. Pöldinger and his colleagues

wondered why as well. " With all due deference to scientific scepticism, " they

wrote, " the reluctance by some authors of recent textbooks on the subject and by

others to concede 5-HTP its place among acknowledged pharmacotherapeutics

routinely applied against depression does not seem

warranted, neither on empirical nor theoretical grounds. " 10 The reason 5-HTP

has been largely ignored by most conventional physicians can be summed up in one

word -- patentability. Like all commercial drugs, SSRIs are patented compounds

that can be marketed exclusively by the companies that own the patent. This

gives them an sole right to market the drug until the patent expires, usually

after 17 years. Exclusivity offers pharmaceutical companies a huge financial

incentive to develop patentable products, and it justifies the enormous

expenditures required to gain FDA approval for the product. Once the patent

expires, though, anyone can market the product generically. The added

competition inevitably forces prices, and consequently profit margins, straight

down. As a naturally occurring substance -- like water, table salt, or vitamin E

-- 5-HTP cannot be patented. Anyone can market 5-HTP, just as anyone can market

vitamins or generic drugs, provided the product meets accepted

standards of quality and purity. With no guarantee of exclusivity, it is rare

for a pharmaceutical company to absorb the hundreds of millions of dollars in

development costs involved in years of laboratory and clinical trials, not to

mention millions more for promotion once the product is " launched.' When faced

with a natural product such as 5-HTP, a pharmaceutical company's typical

response is to study how it works and then try to create/synthesize a brand new

-- and patentable -- molecule that does approximately the same thing. It matters

little whether the synthetic product is as good as or as safe as the natural

one. The only relevant conditions, as far as FDA is concerned, are that the new

product is significantly better than an inactive placebo and that it does not

present an unacceptable risk to the patient. This is an unfortunate fact of life

in the pharmaceutical industry, and we cannot blame pharmaceutical companies for

acting this way. Given the way patent laws and FDA

drug regulations are written, this is the only way they can maximize

profits.One unfortunate consequence of this system is that safe, effective,

natural products such as 5-HTP are rarely evaluated in the large,

well-controlled clinical trials required to gain acceptance by the

medical/government regulatory establishment. The fact that drugs are always

evaluated this way makes it easy to dismiss 5-HTP or other such products as

having " insufficient " support to recommend their use, compared with the Prozacs

of the world. In light of these facts, the only conclusion we can usually draw

about whether the drugs are actually better than the natural products is, " We

don't know, " because the relevant comparative studies are almost never done.

Pöldinger's comparison of 5-HTP and fluvoxamine was indeed a rare event in

pharmaceutical research.With the deck stacked against 5-HTP, it should come as

no surprise that few physicians have ever heard of it, and fewer still are

willing to recommend it.

Nevertheless, Pöldinger's results demonstrate that 5-HTP may be every bit as

good as the SSRIs and probably safer and more tolerable. Although it would

certainly be useful to confirm these results in a large-scale US clinical trial,

given 5-HTP's " generic " nature, the enormous costs of such a trial make it

highly unlikely that anyone will ever run one.