만성적인 정동장애의 식이요법 '데이비드 호킨스"

[문형철]

가능한 빠르게 허리디스크 책을 완성해야 하는 이유가 하나둘씩 생겨나고 있다.

let's go

letting go

for Tardive Dyskinesia

 Charles Tkacz, M.D.1  and David R. Hawkins, M.D.2

This paper is concerned ultimately with the

presentation of a safe, effective and simple

preventive measure for tardive dyskinesia

(TD), a disease completely unknown to us

during our years of early training in the 1950's,

but one which seems now to be increasing in

preval‎ence and severity before our eyes. Each

month brings more journals with more reports

concerning TD: two major articles in

successive months this summer in the

American Journal of Psychiatry; a major article

in the summer issue of the Journal of the

American Academy of Child Psychiatry, and so

on. As seems to be the case so often with

"new" diseases or with iatrogenic diseases, the

articles read like detective stories: "The answers

are here, Doctor, in front of you: but

exactly where?" These are good papers, and

like all good papers, they frequently admit to

the unknown, sometimes contradict each other,

but always show a desperate concern with

trying to unravel the mystery that is TD.

Two themes run through the history of

' Associate Medical Director North Nassau Mental Health

Center 2 Medical Director North Nassau Mental Health

Center

medicine and psychiatry: the theme of iatrogenic

illness, together with the theme of more

or less accidental therapeutic discoveries.

Sometimes the two intertwine. The findings we

present here toward a preventive for TD were

unanticipated, fortuitous, almost unscientific

and anecdotal, yet they point the way toward a

safe and effective preventive for this puzzling

disease.

There is almost universal agreement that TD

is a movement disorder, associated somehow

with long-term use of antipsychotic or

neuroleptic medications. "Tardive" means of

late onset; "dyskinesia" means abnormal

movement. It is considered an extrapyramidal

disorder yet distinct and, in fact, opposite from

other extrapyramidal disorders such as

pseudoparkinsonism.

Early descriptions of the disorder now called

TD were concerned with face and mouth

movements to the point where clumsy terms

like "lingual-facial-buccal dyskinesias", or

"orofacial dyskinesias", or "buc-co-lingualmasticatory

dyskinesias" were used. These

seem all to have given way to the term TD

which the 1975 American Psychiatric

Association Glossary defined as "untoward

effect, appearing after long term use of

antipsychotic drugs with muscle involvement

about the face, neck and trunk, lead-

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 ORTHOMOLECULAR PSYCHIATRY, VOLUME 10, NUMBER 2, 1981, Pp. 119-123

ing to spasms, tics, eye signs, and speech

disturbances." Even there, in 1975, the basic

description was of face and mouth movements,

with no mention of limb movements; yet there

is general agreement now that any striated

muscle can be involved in TD. One other term

is becoming popular: "withdrawal emergent

syndrome", describing a condition very much

like TD but inherently reversible. "Withdrawal

emergent syndrome" (WES) seems to be used

as a term for a mild and reversible form of TD

or perhaps a more benign pediatric form not,

strictly speaking, identical with TD itself. Its

usage seems not to have been solidified yet. It

may even be best for the moment to think of

TD as a group of disorders, rather than one

disorder, or at least to deal with it as two

disorders, one reversible and the other

irreversible. TD then is one of four major

extrapyramidal side effects associated with the

use of neuroleptics or major tranquilizers; the

other three are dystonias (or muscle spasms),

akathisias (restlessness; the "inability to sit

still"), and pseudoparkinson-ism (tremors,

rigidity, akinesias). These three unlike TD, are

usually reversible with discontinuance of

medication; they make their appearance early

in treatment with neuroleptics while TD by

definition appears late.

There is no consensus as to many aspects of

TD: not as to its incidence or preval‎ence, nor

to its cause (except insofar as its being

associated somehow with long term use of

neuroleptics, and even here one finds disagreements),

nor to its neurophysiology, and

certainly not as to its treatment.

There does seem to be a consensus that a

poorly defined "at risk" population exists: that,

for example, TD may be more common among

the elderly (but, as an aside, is this because the

population is elderly, or because the elderly

have been on psychotropics for longer periods

of time?) The "at risk" population may or may

not include patients with organic brain

syndromes and, depending on whose statistics

one cites, the population may be mostly

female. Confounding all this is the fact that

some authors and senior psychiatrists maintain

that a disease resembling TD, with a preval‎ence

as high as 20 percent, has always existed

in chronic psychiatric populations long

before neuroleptics were dreamed of. Popular

examination questions about "schnauz-krampf"

certainly antedated major tranquilizers.

Additional research has centered on whether

TD is associated with long term use of

anticholinergics; on whether certain neuroleptics

as opposed to others are more notorious in

producing TD; on whether it oc-curs more

frequently with certain psychiatric diagnoses as

opposed to others; on whether drug holidays or

intermittent treatments are of any value

prophylactically; and on whether its incidence is

higher among patients who should probably

never have been on neuroleptics (that is, the nonpsychotic).

There is disagreement on all these

points.

The true incidence of TD (that is, the number

of new cases in a population identified over a

period of time) is simply unknown, while the

preval‎ences (the percentages of afflicted patients

in a more or less controlled patient population)

range from less than one percent to almost 60

percent in various reports. One wonders exactly

what this extraordinary range represents. Is it due

to differences in patient populations? Differences

in defining the disease, in agreeing on its

parameters, in the examination process itself? In

using or not using some unknown prophylactic

measure? Compare historically and as only one

example the retrospective finding that using

more oxygen in premature babies in more

advanced premature nurseries led to retrolental

fibroplasia. Then, too, and almost unique in

medicine, the very disease-causing agent we are

discussing — the neuroleptic itself—can mask

and improve the clinical picture when given in

larger dosages.

Since the changes of TD frequently remain

after neuroleptics are discontinued, some

neuropathologists have looked for evidence of

structural changes; there is simply no agreement

here. Researchers seem more concerned with the

role of neurotransmitters and receptors and the

biochemical evidence that many mental and

neurological disorders result from mix-ups in

these infinite combinations of receptors and

chemicals. To oversimplify perhaps: when

schizo-

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phrenia is active, too much dopamine is produced

and accepted at certain receptor sites in

areas of the nervous system concerned with

thoughts and feelings. Neuroleptics like

chlorpromazine block this acceptance, but in a

patient destined to get TD—and of course not

all do—dopamine receptors in certain other

areas of the nervous system, for reasons not

entirely clear, become hypersensi-tized to

whatever dopamine is available following

their chronic blockade. There may be a sheer

increase in the number of dopamine receptors

as well. This is the "Chronic Blockade"

Hypothesis. To recapitulate, two things

happen when a patient is about to develop TD:

dopamine receptors in certain areas of the

nervous system now become exquisitely

sensitive to what little amount of dopamine is

available (which now explains why a patient

with TD looks like a patient with

Parkinsonism overtreated with l-Dopa); and

secondly, perhaps the total number of these

dopamine receptors, probably in areas

involved in motor movements only, increase

in number. This explains why putting a patient

back on neuroleptics (that is, the very

substance which caused the TD to begin with)

relieves the symptoms of TD temporarily.

Conventional Treatment

Current methods for treating TD are inadequate

and sometimes contradictory. If the

pathophysiology is thought to result from

hypersensitivity of receptors to dopamine,

then perhaps substances which reduce the

amount of dopamine in the brain (such as reserpine

or tetrabenazine) should work; in fact,

they do, but at a great expense in side effects

and in unpredictability.

Other neurotransmitters, such as choline and

its precursers (lecithin, deanol) have been used

to equalize other neurotransmitter imbalances

thought to be present in TD. Apomorphine in

small dosage has been used, as well as

benzodiazepines and sodium valproate.

Clonazepam, ECT, lithium, even l-Dopa itself

(in a sort of paradigm of making something

better by first making it worse) have all

been used. Friedhoff, with l-Dopa, and Kunin,

with manganese, have suggested a sort of

prophylaxis using these substances together with

neuroleptics and the use of lithium has been

suggested prophylactically as well. With one

more exception—the one we will present later—

these represent the only instances of

pharmacologic prophylaxis of TD. Other

discussions of prophylaxis center on

discontinuing the neuroleptic once TD is

identified; on encouraging drug holidays (although

there is now evidence that this may

increase the preval‎ence of TD); and on eliminating

the use of neuroleptics in possible "at

risk" patients such as the elderly, the organically

impaired, the female. The only measure that

seems to work predictably is increasing the

dosage of neuroleptics in the patient, a measure

proclaimed self-defeating since it seems to "hide"

the TD while escalating its pathophysiology, yet

no studies seem to exist to confirm‎ this

impression.

Our Observation

We became aware during the summer of 1978

that while reports concerning TD were appearing

with alarming frequency and an almost infectious

concern, we ourselves were seeing only patients

who were already diagnosed elsewhere as TD, or

patients whose TD symptoms were present on admission

to our facilities (a busy private mental

health center; a busy hospital practice). If we

were not diagnosing cases, or "missing" cases,

this would soon reveal itself because of our

liberal use of cross-consultation a-mong

ourselves and our equally liberal use of

neurological consultations, particularly among

our hospitalized patients, and because of reports

by staff, by relatives, by patients. Yet we were

not exactly unfamiliar with this disorder; we and

our staff were seeing enough cases among our

new referrals, and at clinical conferences, and

among patients at governmental hospitals with

which we were affiliated. We saw the entire

spectrum, from mild and cosmetic, to devastating.

A little explanation of the history of our Center

is in order now. The North Nassau Mental Health

Center is a busy center which has been active for

over 20 years. It is a clinic licensed by the New

York State Department of Mental Health. During

the past 15

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years, we have been heavily involved in using

orthomolecular treatment methods elucidated in

Hawkins and Pauling (1973).

Our results were as successful and pleasing to

us as they were provocative and controversial

to others. Our methods included using

orthomolecular principles (only niacin and

niacinamide at first), together with traditional

psychiatric treatments including neuroleptics,

ECT when indicated, various "talking"

therapies when indicated, and a large dose of

what there was no name for at the time but

which we now recognize in retrospect was faith

and a lot of preventive holistic health. An

inevitable pragmatic pharmacopeia of

orthomolecular prepar ations (now used at

many centers across the U.S. and in fact the.

world) evolved. Our preparations whose

formulation was arrived at empirically over the

first years of our existence, contained:

Ascorbic Acid 333mg

Either Niacinamide (Formula 1)

or Niacin (Formula 2) 333mg

Pyridoxine HC1 66mg

d-AlphaTocopheryl Acetate 66.I.U.

The dosages prescribed ranged from four to

twelve capsules a day given with meals, in

divided dosages. Dosages usually tended to be

at the higher end of the scale after having been

increased gradually. Side reactions were almost

always those attributable to niacin or to

niacinamide (peripheral flush; mild

gastrointestinal upsets), and were handled by

reducing dosages temporarily. This preparation

was easily the most popularly prescribed item

among our staff. We found to our astonishment

that among our patient population (10,000

outpatients during a ten-year period; 1,000 inpatients

at our hospitals during a ten-year

period) not one case of tardive dyskinesia

developed in any patient (who did not have TD

to begin with) who was placed on this

formulation as well as any neuroleptic in any

dosage at all. Patients wo did not receive

neuroleptics, regardless of what else was done,

were of course not included in these statistics.

There is more than enough precedent for

postulating a biochemical mechanism for

preventing tardive dyskinesia with one or more

vitamins. Pyridoxine, for example,

aside from being important in blood and central

nervous system metabolism, has several other

functions in the body: the decarboxylation of

various substances; the transamination of amino

acids; the conversion of tryptophan to niacin;

the decarboxylation of dopa to dopamine by

acting as the source of a co-factor, pyridoxyl-5-

P04.

It is easy to surmise pyridoxine's being involved

somehow in the physiology of movement

and movement disorders. There were

simply no other common denominators other

than vitamins to explain our good fortune but

what we cannot answer now is which of the

constituents, or which combination, is

responsible for this phenomenon. Secondly, and

remembering that TD is in many respects

similar to the movement disorder induced by

excessive l-Dopa, Yahr reported reversal of this

movement disorder with massive dosages of

oral pyridoxine. Thirdly, DeVeaugh-Ceiss and

Manion have published a study showing that

"high doses of pyridoxine may reduce the

frequency and severity of involuntary

movements in tardive dyskinesia" which has

already been diagnosed.

To our knowledge, then, this is the first study

in which any vitamin or combination of

vitamins is offered as the prophylaxis for

tardive dyskinesia. We are not biochemists but

rather biochemically oriented psychiatrists, yet

we are in the process of submitting our findings

to biochemical analysis and to further statistical

analysis, under the very likely assumption that

not all four constituents of our formulas No. 1

and No. 2 are necessary to prevent TD. Our

impression is that pyridoxine alone seems not to

be sufficient as a preventive although we have

reason to believe it decreases the incidence and

severity of TD when used alone. One can easily

envision pathways by which one or all of the

other three constituents may facilitate the anti-

TD effects of pyridoxine.

Summary

Tardive dyskinesia as a disease entity is reviewed

briefly, and its current management and

unsatisfactory treatment is discussed. When one

reviews the literature one finds that the use of

preventives against TD, when

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 PREVENTING TARDIVE DYSKINESIA

neuroleptics are indicated, is almost nil. We

herewith submit evidence that indicates the

combined use of any neuroleptic given together

with a megavitamin preparation well known in

orthomolecular circles, has failed to yield

evidence of a single case of TD.

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