Re: Pfeiffer and depression

[Guest guest]

Thank you, . That's a good list. I recognize many of the things

my children take and most together are effective and harmless,

really. This is what many nutritionists recommend even without

testing, though I'm sure amounts were tailored to you. I'm really

glad to know this helped.

I am a bit disappointed that DANs are still going by the serotonin

theory of depression though. They need to rethink the souces of some

of these theories, though it's good that Pfieffer seeks information

on underlying malabsorbtion and nutritionalal imbalance issues--

which is why DANs rock. Study on the source of the " serotonin

imbalance " theory of depression:

http://medicine.plosjournals.org/perlserv/?request=get-

document & doi=10.1371/journal.pmed.0020392

The Serotonin Hypothesis

In 1965, ph Schildkraut put forth the hypothesis that depression

was associated with low levels of norepinephrine [6], and later

researchers theorized that serotonin was the neurotransmitter of

interest [7]. In subsequent years, there were numerous attempts to

identify reproducible neurochemical alterations in the nervous

systems of patients diagnosed with depression. For instance,

researchers compared levels of serotonin metabolites in the

cerebrospinal fluid of clinically depressed suicidal patients to

controls, but the primary literature is mixed and plagued with

methodological difficulties such as very small sample sizes and

uncontrolled confounding variables. In a recent review of these

studies, the chairman of the German Medical Board and colleagues

stated, " Reported associations of subgroups of suicidal behavior

(e.g. violent suicide attempts) with low CSF–5HIAA [serotonin]

concentrations are likely to represent somewhat premature

translations of findings from studies that have flaws in methodology "

[8]. Attempts were also made to induce depression by depleting

serotonin levels, but these experiments reaped no consistent results

[9]. Likewise, researchers found that huge increases in brain

serotonin, arrived at by administering high-dose L-tryptophan, were

ineffective at relieving depression [10].

(Illustration: Margaret Shear, Public Library of Science)

Contemporary neuroscience research has failed to confirm any

serotonergic lesion in any mental disorder, and has in fact provided

significant counterevidence to the explanation of a simple

neurotransmitter deficiency. Modern neuroscience has instead shown

that the brain is vastly complex and poorly understood [11]. While

neuroscience is a rapidly advancing field, to propose that

researchers can objectively identify a " chemical imbalance " at the

molecular level is not compatible with the extant science. In fact,

there is no scientifically established ideal " chemical balance " of

serotonin, let alone an identifiable pathological imbalance. To

equate the impressive recent achievements of neuroscience with

support for the serotonin hypothesis is a mistake.

With direct proof of serotonin deficiency in any mental disorder

lacking, the claimed efficacy of SSRIs is often cited as indirect

support for the serotonin hypothesis. Yet, this ex juvantibus line of

reasoning (i.e., reasoning " backwards " to make assumptions about

disease causation based on the response of the disease to a

treatment) is logically problematic—the fact that aspirin cures

headaches does not prove that headaches are due to low levels of

aspirin in the brain. Serotonin researchers from the US National

Institute of Mental Health Laboratory of Clinical Science clearly

state, " [T]he demonstrated efficacy of selective serotonin reuptake

inhibitors…cannot be used as primary evidence for serotonergic

dysfunction in the pathophysiology of these disorders " [12].

Reasoning backwards, from SSRI efficacy to presumed serotonin

deficiency, is thus highly contested. The validity of this reasoning

becomes even more unlikely when one considers recent studies that

even call into question the very efficacy of the SSRIs. Irving Kirsch

and colleagues, using the Freedom of Information Act, gained access

to all clinical trials of antidepressants submitted to the Food and

Drug Administration (FDA) by the pharmaceutical companies for

medication approval. When the published and unpublished trials were

pooled, the placebo duplicated about 80% of the antidepressant

response [13]; 57% of these pharmaceutical company–funded trials

failed to show a statistically significant difference between

antidepressant and inert placebo [14]. A recent Cochrane review

suggests that these results are inflated as compared to trials that

use an active placebo [15]. This modest efficacy and extremely high

rate of placebo response are not seen in the treatment of well-

studied imbalances such as insulin deficiency, and casts doubt on the

serotonin hypothesis.

Also problematic for the serotonin hypothesis is the growing body of

research comparing SSRIs to interventions that do not target

serotonin specifically. For instance, a Cochrane systematic review

found no major difference in efficacy between SSRIs and tricyclic

antidepressants [16]. In addition, in randomized controlled trials,

buproprion [17] and reboxetine [18] were just as effective as the

SSRIs in the treatment of depression, yet neither affects serotonin

to any significant degree. St. 's Wort [19] and placebo [20] have

outperformed SSRIs in recent randomized controlled trials. Exercise

was found to be as effective as the SSRI sertraline in a randomized

controlled trial [21]. The research and development activities of

pharmaceutical companies also illustrate a diminishing role for

serotonergic intervention—Eli Lilly, the company that produced

fluoxetine (Prozac), recently released duloxetine, an antidepressant

designed to impact norepinephrine as well as serotonin. The evidence

presented above thus seems incompatible with a specific serotonergic

lesion in depression.

Although SSRIs are considered " antidepressants, " they are FDA-

approved treatments for eight separate psychiatric diagnoses, ranging

from social anxiety disorder to obsessive-compulsive disorder to

premenstrual dysphoric disorder. Some consumer advertisements (such

as the Zoloft and Paxil Web sites) promote the serotonin hypothesis,

not just for depression, but also for some of these other diagnostic

categories [22,23]. Thus, for the serotonin hypothesis to be correct

as currently presented, serotonin regulation would need to be the

cause (and remedy) of each of these disorders [24]. This is

improbable, and no one has yet proposed a cogent theory explaining

how a singular putative neurochemical abnormality could result in so

many wildly differing behavioral manifestations.

In short, there exists no rigorous corroboration of the serotonin

theory, and a significant body of contradictory evidence. Far from

being a radical line of thought, doubts about the serotonin

hypothesis are well acknowledged by many researchers, including frank

statements from prominent psychiatrists, some of whom are even

enthusiastic proponents of SSRI medications (see Table...