THE PHARMACOLOGICAL
APPROACH TO TREATING
CHILDHOOD PSYCHOSES: THEORETICAL BASIS
Renato COCCHI. A
neurologist and a medical psychologist
(Italian
translation) // Testo in italiano
Summary
Drug treatment of childhood psychoses is
founded on the ever growing evidence of a primitive biological disturbance, and
on the need to recognize the human organism's inseparable bio-psychic unit. The
American idea, which postulated a single biological error to be corrected by
just one drug, we feel as impracticable for now and our own approach, which we
have been operating for at least eight years (documented in the videotapes) is
based on the following premises:
a. Like any other illness, infantile
psychoses present symptoms of endogenous stress. They come from the illness
itself (not to mention the secondary psychological stress too), symptoms that
we can treat through drugs;
b. The symptoms, signs of dysfunction in
one or more neurochemical pathways, can be rectified working backwards by
drugs. In this way we can reduce the presumed general neurochemical imbalance
and the current symptoms of the illness itself.
In this approach the use of physiological
substances occupies prime position, while we can avoid the use of neuroleptics
until preadolescence. This type of therapy is perfectly compatible with any
other kind of intervention (psychological, in its broad meaning) which is then
eased. Various cases treated in this way were presented, with all their
specific indications, in the videotape section at the Urbino Conference.
Key words: Childhood psychoses; drug therapy; theoretical bases.
Autism
Drug modulation of stress reactions
Mental retardation
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The theoretical bases of the drug treatments
that I have used in cases of infantile psychoses since 1981 are not simple.
Nevertheless, I believe they have their own clear line.
First I feel the need to outline a series of
premises that I believe to be indispensable in understanding both my work and
that of other professionals. Even though not using pharmacological methods,
these latter persons still maintain they obtain appreciable results.
Excluding behavioural therapy, which I
consider to be a quite different technique, there can only be two answers:
either some of us are not interpreting their own work properly or we are all
telling the truth, even if it is only a partial truth.
Until proven wrong I sustain the second
hypothesis.
I must say straight away however, that when
bad breasts, empty fortresses and fish-children become like faith objects. They
went beyond the boundaries of science, as objects verifiable in experimental
conditions, or at least foreseeable with a large statistic approximation. It is
one thing to describe a type of behaviour, but its interpretation is quite
another.
The latter, expressed in metaphorical terms,
gets to impose an ideological straight jacket on the parents. The risks are
many, ranging from a useless guilt attribution to the parents themselves
(should that have any sense) to a waste of precious time in curing the child.
Along these lines I am perfectly according
to the ideas of Ritvo and Laxer (1983).
I have already said that I do not believe
psychological treatment of a psychotic child as therapeutically wrong, but a
very incomplete approach.
By the videotaped case of pharmacological
therapy started 1982 (Cocchi 1990a) here presented, I should to make clear that
what I am doing is not the result of any recent conversion.
For a long time now I maintained that
infantile psychoses not only had biological bases, (see Cordella 1989c &
1990 for an outline of the problem). So I believe that a biological approach is
one indispensable method to be able to tackle the problem with the largest
degree of success.
Despite this, unlike many other colleagues,
I have always advised parents to seek other integrative therapies. Very often
however, I have had to go into "the catacombs." That is to say I have
had to, and still have to, accept that the parents deny that the child is
undergoing drug therapy. Only in this way they may obtain permission to profit
from other treatments offered by the public health services.
This too, unfortunately, is a characteristic
of the drug approach today in Italy. Here the systematic lack of knowledge on
the use of psychodrugs does not drive to "we don't know," but rather
to the more debatable "we don't want to."
About psychological aspects, in every
illness, and in infantile psychoses, there is always a negative psychological
element, secondary to the illness itself. The important thing is not to confuse
this, which is a secondary phenomena always found, with primary cause.
In terminal illness such a cancer, this
psychological aspect is receiving attention and treatment, as it is right and
logical. Nobody is under the illusion that it can invert the fatal course of
the illness. This is the mistake that ran for years in infantile psychoses and
I believe that unfortunately it will go on. As the result of which, 20-years
ago autistic children are now autistic adults.
Given that they have not become
schizophrenics for example, their treatment is even more difficult. By speaking
through my own experience, something can still be done, especially on
behaviour.
I therefore come to the end of this part,
which is not a mere pouring out of my personal discomfort. It is rather a
simple report and warning to those wishing to follow the pharmacological approach
in treating infantile psychoses.
I have not yet finished with the premises
that are indispensable in understanding my work.
From at least 20 years I think that the
brain mechanisms do not function based on a series oæ_ linear cause and effect
relationships. A multivariable system seems more fitting, in which the many
mechanisms are interconnected, even if there is some form of hierarchy.
And so it follows: 1. That one
neurotransmitter will never be the sole cause of complex syndromes such as infantile
psychoses; 2. That the therapy could never be based on one drug. This works
even for vitamin B6 that enters about 60 different brain metabolism mechanisms.
I have been using it for the past 15 years if not more.
The polytherapy that I normally use in child
psychoses allows low dosages always, a balance between the various drugs,
_synergism, no possibility of habit forming and the possibility, if carried out
well, of an interruption without rebound phenomena.
Nevertheless, after a certain length of time
from interruption, there is a reversal to the previous state. This proves that
the therapy, up to that moment, at least, has been only a replacement therapy.
Unfortunately, many medical practitioners
have no clear notion of what "replacement therapy" actually means.
So, on interruption of the treatment, they confuse a return to the pre-cure
condition with the phenomenon of habit forming which is quite different.
A polytherapy acting on the CNS should have
carried out, in my view, with physiological substances as far as possible. That
is a way to reduce the much feared but little proven risks of toxicity.
As far as vitamins are concerned, the human
brain uses them in different ways depending on the areas (Baker et al., 1984).
It is therefore not absurd that a dysfunction in some brain structured such as
the Pons and the Midbrain that can be the cause of most cases of squint. So it
can be corrected also by administering the two vitamins mostly used in these
structures, pyridoxine and biotin.
I have already published my experience in
this field, on spontaneous nystagmus (Cocchi & Branchesi, 1989; Cocchi
& Maniscalco, 1990) as I will indeed publish my work on convergent squint.
It follows that, apart from the rest of the
clinical situation, in the presence of the symptoms "spontaneous
nystagmus" or "convergent squint" (often associated), - and if a
refractive origin of the squint can be excluded - then these two physiological
substances are well indicated.
In other words, a whole series of symptoms
can point towards the malfunctioning neurochemical mechanisms. While saying
this however, it is not necessarily true that a functional deficiency
corresponds with a deficit in the neurotransmitter involved.
With infantile psychoses there is often
initial hypersensitivity, particularly regarding sound but also, it seems, the
other sensory canals.
Since it is by now well accepted that the
sensory canals utilise mainly the glutamate as a neurotransmitter (Fagg, 1985)
hypersensitivity of this type must lead us to think not of a deficit, but of an
excess of the glutamate.
The results of this magnification will be a
sensitive-like stress (as for example when a normal individual finds himself in
the presence of a continuous excessive noise). In the condition of acoustic hypersensitivity,
even normal sounds reach the pain threshold and produce ulterior stress.
If this should happen through all perceptive
canals, there would be a blockage in the passage of these stimuli, which seems
typical of infantile psychoses (Ornitz et al., 1985).
The glutamate does not seem to have a
limiting step for its synthesis in the CNS, unlike the case of the GAD for GABA
(Baxter, 1976). We have to remember that GABA finds the glutamate itself as its
most important precursor.
We know that the glutamate largely arrives
in the CNS either as a derivative of glutamine or from glucose through the
Krebs cycle (Ward, Thanki & Bradford, 1983). So, the only way to limit its
production is the reducing of the intake of these two substances, by limiting the
introduction of foods which are rich in these respects: Broth for glutamine,
sweets for glucose (Cocchi, 1990b) or a general reduction of food intake as a
whole.
Here are three more symptoms of great
informative value.
As for diet habits, another variable appears:
The need for pasta or bread, found often in these children may suggest another
attempt at compensation. By now it is certain that cereals, and among them
wheat, contain equally two benzodiazepines, diazepam and N-desmethyldiazepam
(De Blas, 1988. Then benzodiazepines are moreover natural substances though
originally discovered as synthetic products. The question arises about whether
it is not the need for these substances that drives the children towards these
foods.
Already, with regards auto-aggression, you
will have understood that the organism tries to compensate, before falling into
a more deficient functional state (Cocchi & Bonaduce, 1988). This is a
common physiological fact, even if not largely considered in relation to brain
functioning.
Every kind of compensating will work as
partial though, otherwise, if it were 100% efficient, we would have no illness.
The most probable risk fought by
auto-aggression is cardiac collapse. An increase in adrenergic and
noradrenergic peripheral and cortisolic incretion is one way to limit this risk
(Cocchi & Bonaduce, 1988).
Difficulty in falling asleep is always a
sign of a central serotoninergic deficit (Puizillout et al., 1981). Then some
sufferers have a glass of milk at night before retiring, milk being a richest
source of triptophane (Geigy Scientific Tables, 1981) the precursor of
serotonin.
We need do not forgot though that an
increase in corticosteroid incretion can promote the synthesis of serotonin
(Rastogi & Singhal, 1978). Banging the head against the headboard or simply
swinging or rocking motion could serve to induce sleep.
Another element to consider is the
relationship between CNS and the Vegetative NS.
Now it is clearly wrong to call the
Vegetative NS as "autonomous," since its activation by the
hypothalamus (Goto et al., 1985), especially due to intense and chronic stress.
This activation is prevalently vagal, parasympathetic.
A tendency towards sudden diarrhoea, of
brief duration and without any specific reason is another symptom of notable
value. Here we find the usefulness of understanding all the symptoms, because
they give us reference to the central mechanisms.
The knowledge of 40-50 symptoms of this kind
can therefore give us information as to the cerebral and cerebellar functioning
of the glutamate, GABA, serotonin, noradrenalin, acetylcholine, dopamine, the
endogenous opiates, just to mention the most well kown neurotransmitters. It
has been demonstrated how under stress all these neurotransmitters can be
involved simultaneously, as the effect of an excess of GABA B inhibition (see
later on, for references).
I think that the critical point is indeed
the stress. From this we can start again to attempt a full comprehension of the
reasons for adopting a pharmacotherapy like mine. This could also be useful to
understand the possible cause of infantile psychoses.
Corticosteroid incretion from stress,
produces a neurotoxic effect on the cortisolic Hippocampus receptors, which
reduce its ability to retroactively inhibit corticosteroid incretion. In this
way the capacity of the organism to react adequately to subsequent stress
already goes down.
Moreover, there comes about an increase
first in the hypersensitive effect, and then in the neurotoxic effect of the
glutamate, also on the frontal cortex (see for a review: Cordella 1989a and
1989b).
This however is a secondary mechanism, very
important for a general understanding, but not yet explicating as to the
underlying cause. To understand the latter we should look back at the relationship
between stress and GABA.
Under the influence of a stressing agent,
type A GABAergic receptors, namely those activated by the benzodiazepines,
change their conformation rapidly, by that reducing type A GABAergic
inhibition. (Medina et al., 1983). This may be only a temporary event, but if
the stress is very intense or lasts a long time this could become a stable
condition (Braestrup & Nielsen, 1983; Biggio et al., 1984) which drives to
a succession of events such as:
- Lower consumption of GABA by type A
receptors, reduced in number;
- Following the relative excess of GABA
available, an increase in type _B GABAergic inhibition follows. This inhibits
the cerebral activity of serotonin (Ketelaars & Bruinvels, 1988), dopamine
(Bovery et al., 1980), noradrenaline (Suzdac & Gianutsos 1985a, 1985b) and
acetylcholine (Estevez et al., 1984 Sidel et al., 1988);
- An increase in endogenous opiates and
endorphines (Cocchi, 1990d);
- Hypothalamus activation of peripheral
parasympathetic stimulation (Goto et al., 1985);
- The peripheral necessity for sympathetic
compensation (Cocchi & Bonaduce, 1988; Cocchi, 1990d);
- Reduced synthesis of GABA due to the
partial blocking of GAD (Baxter, 1976; Loescher, 1980).
- Following the reduced synthesis of GABA,
retroactive increase of _the glutamate in the CNS, with an increase in
sensitivity and the risk of neurotoxicity.
This, in brief is what already known.
The stress that most likely sets off this
chain of events is of pre-, peri-, neonatal nature (Cordella 1989a, 1989b) not
serious enough to cause massive neuronal damage. If something like this in fact
happens, then the diagnosis would be infantile cerebral palsy, mental
deficiency, and epilepsy).
Evidently, a newborn child starting off life
under these conditions can, right from the start, have a lower emotive
threshold. So, all the accompanying neurovegetative, psychological, and
secondary psychodynamic consequences can follow.
Often this is not the picture right from
birth though.
The case of the autistic child is well known
however, the child who for the first year and part or all of the second year of
life not only shows any sign of the psychosis but develops more quickly
autonomous walking and language.
A retrospective investigation would show
that, given the ability to evaluate the health status, there were symptoms of
neurovegetative and behavioural damage (Negri, 1990) but their importance is
limited to risk signals, moreover not yet quantified.
Then the breakpoint and regression came out,
with the appearance of quite clearly psychotic symptoms.
Is it possible to interpret this event as
linked to stress too? I think yes, if we bear in mind three things:
1. That stress can also have an internal
metabolic triggering agent;
2. That the second year of life is a very
delicate time in which the functioning of cerebral mechanisms that have reached
maturity in this time comes into play. Some brain areas could have subtle
damages by the primary cause, without letting it known until this point, what
their state of a malfunction is.
3. That the functional imbalance between
intact and damaged cerebral areas could itself be the cause of ulterior stress,
reaching levels at which the organism is no longer able to control.
In Downs syndrome, the continuous metabolic
stress, caused by the presence of the third chromosome 21 and by the consequent
dosage effect is much more likely to set off a psychotic onset due to the
chronic stimulus and to the (experimentally documented) reduction in the
capacity to respond to the stress (Cocchi, 1989).
Given parity of stressing agents, both in
Downs and normal children, a psychotic onset does not come about always. The
reason is that this also depends on the variability of the individual
constitution to deal with stress (Vogel, 1985).
This is a very general introduction to a
problem that would require a seminar of at least 30 hours to be exhaustive.
It is hoping however, that the
multiviariability of the mechanisms involved will have interested many people.
As seen, all the therapies proposed, from vitamin B6, cofactor of the GAD and
therefore involved in GABA synthesis, to phenfluramine, naltrexone, diet
correction, and psychological intervention of a prevalent anxiolytic nature,
can have some effect.
Each of them in fact, can correct the
relative malfunctioning neurochemical mechanism. Each will only be ever a
partial therapy.
Not only this but the dosage increasing in
monotherapy, from drugs to stimulation, can induce exacerbation as the cause of
a further neurochemical imbalance from a therapy stress. If this seems far
fetched just think of what happens in antibiotic therapy given to already
fragile infants, with infantile CP or mental deficiency for example. We should
bear in mind that 250,000 units of penicillin are enough to send an adult cat
into a convulsion (Van Gelder et al., 1983). The convulsive reaction is now
considered as an imbalance between inhibiting neurotransmitters (GABA types)
and excitatory ones (such as glutamate) (Meldrum, 1984).
With what criteria then can one start a drug
therapy in the psychotic child?
To sum it up:
1. Evaluate the symptoms to figure out the
particular neurochemical imbalance in that child;
2. Start correction by restoring the
functionality of the type A GABAergic receptor; The best antistress drugs are, as
we known, the benzodiazepines, and, among them, the best one is still diazepam.
3. Use low drug dosages in order tï avoid
metabolic stress action brought on by the drugs.
4. Use, as far as possible, physiological
substances;
5. Do not expect or imply short term
resolutions, but work on small and successive progressions; one must think in
terms of years of pharmacological therapy (Cocchi, 1990c);
6. Be prepared for moments of stasis or
regression, which can always happen and should be interpreted (Cocchi, 1990b).
A therapy that was going well, can become suddenly ineffective in controlling
an added stress (often of seasonal nature);
7. Do not ignore eventual overstimulating
effects, the so called "paradoxical" effects of the drugs used
(Cocchi, 1990c);
8. Yet not we do not know all the variables.
So, success may be modest or not at all in about 10% of cases, at least in my
experience (Cocchi, 1990c);
9. Start the therapy as soon as possible.
This is also the only way to hope for a larger impact on the neuronal
plasticity, at least of dendritic and synaptic development.
No doubt the video tapes I presented and the
two cases described in detail (Cocchi 1990a & 1990b) will have clarified,
at least partly, the practical side of this approach. Due to its nature, we can
only individually tailor it as stress responses vary from child to child for
reasons of genetic and acquired characteristics (Vogel, 1985). Above all they
will be variable responses, with a tendency to be less efficacious depending on
the age and the duration of the stress.
It is the illness itself, like any illness,
the continuous source of stress, even if we would like to see it exclusively
from a psychological point of view.
This means unlucky that we cannot ever have
therapeutic protocol, a new transitional object for all those people who no
longer know how to be clinicians. I hope I will find time to write a book, or
to design a computer program that covers all the variables I know and have
experimented with. So, not only my experiences can be repeated, but enriched by
the findings of others.
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Printed on It. J. Intellect. Impair. 1990,
3: 185-193
Author's address: dr Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Italian translation // Testo in italiano
Autism
Drug modulation of stress reactions
Mental retardation
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