MEDICATION IN AUTISTIC CHILDREN
MadisonDoctrine Web Topic 000821A
by Ralph Ankenman, M.D. (not peer-reviewed)
Early DUAL-PURPOSE multiple medication regime to modify the course
of
AUTISM and autistic-like symptoms of PERVASIVE DEVELOPMENTAL DISORDER.
WHATEVER THE ORIGIN OF AUTISTIC BEHAVIOR PATTERNS,
THE LONGER THEY ARE PRACTICED, THE MORE THEY BECOME PART OF THE
INDIVIDUAL'S BEHAVIORAL HABITS. MEDICATION NOW OFFERS
EARLY HELP TO ALTER AUTISTIC BEHAVIOR PATTERNS.
Overview: 1. Early intervention can help modify
the outcome of the effect of Autism in children. Until recently,
medication therapies given for these disorders did little more than
provide calming in a general way. Now there are more specific
medications that a) provide benefits in improving socialization (Atypical
Antipsychotics), and b) lower the obsessive-compulsive drives which
consume so much time and mental focus. (Selective Serotonin Reuptake
Inhibitors, or SSRI's). Furthermore, there have always been
instances where autistic individuals have made sudden shifts toward
socialization and communication. There may now be some clues
how these changes can be effected. It may be that medical science
is finally approaching the point where the long-sought "cure" for
Autism will be found.
2. Besides the medications which reduce the "autistic symptoms" in
autistic individuals, there are also medical treatments for the symptoms
occurring because autistic individuals do not mature at a normal
pace. These non-specific behavioral upsets related to immaturity
such as sleep disturbances, hyperactivity, rage and aggression may
present more day-to-day difficulty than the Autism itself.
Use of "Autism-specific" medications along with general stabilizing medications
has produced such a marked improvement in the function of autistic and autistic-like
individuals that an attempt at intervention seems advisable as soon as autistic
symptoms are demonstrated.
Outline:
I.THE MAJOR MEDICATIONS TO REVERSE
THE COURSE OF AUTISM.
I. THE MAJOR MEDICATIONS
TO REVERSE THE COURSE OF AUTISM.
A. Atypical Antipsychotics. These medications are marketed for
treatment of Schizophrenia, being especially beneficial in treating the "negative
symptoms" --that is, the various behavior patterns of mental dullness and
social withdrawal. However, the tendency to live in an "internal emotional
life," rather than having a balanced emotional exchange between the inner
and outer world, is a "habit" shared by Schizophrenia, Autism and other psychiatric
states. The action of the Atypical Antipsychotics helps such individuals "lubricate" their
inner drive to socialize with others. This action occurs in individuals
who do not have psychosis as a part of their disorder. The term "Atypical
Antipsychotic" is therefore unfortunate. I have thus dubbed this group "Prosocialization" medications.
Other nicknames are "Social Lubricants" or "Get-out-of-Living-in-Your-Own-Head
Pills."
1. Instant improvement! Caregivers have frequently
observed that most autistic individuals will have some behaviors which
are "less autistic". ( For example, some individuals practice extensive
autistic-like self-stimulation but are capable of showing normal affection.)
The Atypical Antipsychotics seem to improve the amount of non-autistic
socially interactive behavior -- even from the first day of treatment.
This is especially true in younger children.
Case A. A 25 year old
highly autistic individual who had Bipolar Disorder was
mood stable on a complicated medication regime but still
highly involved in autistic self-stimulation. In 1994,
after 4 days of being on risperidone at the low dose
of 1.0 mg a day he came up to his mother and spontaneously
hugged her for the first time.
Case B. A 5-year-old girl with
considerable autistic behaviors began moving into the play
area of her day school and tolerating the presence of her
school mates within a week of starting on 1/40mg of risperdone.
2. Low dose therapy. These medications are
very potent. For example, the dose for risperdone to treat
Schizophrenia was supposed to be 6 mg/day. But individuals
with first occasion schizophrenic symptoms will average 2 mg.
Some non-schizophrenic adults have found 0.5 mg a day too activating
and still gained benefit at 0.25 mg. or even 0.125 mg. In
children ages 2 to 4 a starting dose of risperdone may
be one or two drops a day of the liquid. (1/40 to 1/20 a mg)
working up slowly every one to four weeks.
B. Link to Web Memo Description and Differences
Among the Various Atypical Antipsychotics.
Includes risperidone (Risperdal), quetiapine (Seroquel), olanzepine (Zyprexa),
and clozapine (Clozaril).
C. Treatment of Obsessive-Compulsive Symptoms
with SSRI's and Other Serotonergic Agents.
1. Obsessive-compulsive symptoms are a major impediment preventing
the autistic individual from functioning in the real world. They
especially involve repetitions in eating, dressing, or lining
up objects in order. Rather than being able to interact and grow
with the outside world, the compulsive-acting autistic individual
seeks the feeling of control by requiring order and repetition.
It is sometimes noted that treatment with Atypical Antipsychotics
will move an autistic child out of internalize self-stimulation
into obsessive compulsive activities --as a sort of first, highly
controlled step out of its inner world. The SSRI antidepressants
have a proven ability to suppress obsessive-compulsive symptoms
by switching off the overactive circuit between the frontal lobe
and nuclei in the limbic system. When these agents are given
in children, they often produce rapid improvement in symptoms
at relatively low doses.
Case C. A 4-year-old boy
had considerable autistic repetitive habits and played very
little with toys. After being placed on 1/40 mg of Risperdal.
He begin taking an interest in the books in the household ,
and would line them up in a line across the room, becoming
frustrated when he came to a wall. This compulsive drive was
improved when Prozac was started.
The problem of overactivation: In many individuals the
use of the SSRI antidepressants causes overactivation - sometimes
seen very soon after initiation, sometimes occurring after
weeks. There may be poor nighttime sleep, increased aggressive
behavior, even mood swings of bipolar type. These medications
should be introduced slowly and kept at low, effective doses
until there is assurance that overactivation will not occur.
(Note that occasionally these medications may paradoxically
cause increased obsessive-compulsive behaviors.)
2. Link to web memo Description and Differences Among
the Various Serotonin Re-uptake Antipsychotics. Includes fluoxetine
(Prozac), sertraline (Zoloft), citralopram (Celexa), paroxetine (Paxil),
fluvoxamine (Luvox), and chloripramine (Anafranil)
D. Treatment of Obsessive-Compulsion with
Other Medications. Many developmentally-disabled individuals do not
tolerate even low levels of SSRI medications to treat obsessive-compulsive
symptoms. They frequently become too activated or even agitated.
An alternate treatment regime is to use the medications trazodone
and buspirone (BuSpar) alone, in combination, or together with a
low dose of an SSRI.
II. GENERAL STABILIZATION MEDICATION
AND TECHNIQUES ADD TO THE SPECIFIC THERAPEUTIC EFFECTS.
Besides the very specific benefits of the Atypical Antipsychotics
and Serotonin Reuptake Antidepressants, other medications can provide
for stabilization of general physiological upsets which are common
to all individuals who have disruption of normal maturation processes. Without
such stabilization, the more specific medications may not be effective
or may lose their effectiveness.
A. Sleep. Many individuals have difficulty establishing stable sleep
patterns, which in turn prevents normal maturation. There is no absolute
formula for providing sleep stabilization. It is an area that is still trial
and error in each individual case. Now that there are medications that make
major changes in the foundational problems of Autism, clinicians can work on
more standardized regimes for sleep stabilization.
1. Alpha-2-Agonists- Turning off Adrenaline
Arousal of the Brain. Many individuals do not sleep well because
they cannot turn off the adrenaline drive of the brain. They may
have difficulty going to sleep, or they may wake up after sleeping
four hours ready to play or begin repetitious behaviors. The most
likely class of medications to stabilize this problem is the Alpha-2-agonists.
These medications stimulate those particular receptors of the adrenaline
nerves which lower activity of these nerves -- thus prolonging
the time of rest. Link to web memo Alpha-2-Agonists including
clonidine (Catapres) and guanfacine (Tenex).
2. Other Medications for Sleep:
These must be given on an individualized trial-and-error basis. In fact,
many of them will have negative effects for a significant number of individuals.
a) Antihistamines
Diphenhydramine (Benadryl), hydroximine (Atarax, Visteril), promethazine
(Phenergan). These are sedating because they are antihistamines.
They also have anticholinergic activities that may cause confusion. In
general they last 4 hours.
Periactin. Another antihistamine, but one which
has a serotonin blocking effect. May help in sleep problems
due to the serotonin antidepressants, but in general is
not much better.
b) Antidepressants
Trazodone (Desyrel) -an antidepressant commonly used for sleep.
Can cause a "hangover" in the morning. Starting dose may be as
low as 6.25 at night (one eighth of 50 mg tablet). If it works, the effect
tends to persist with no addiction or tolerance. (Note the caution about
excess penile erections as a side effect.)
Nefazodone (Serzone)- similar to trazodone but less sedating.
May cause activation. Is supposed to stabilize sleep by
improving REM (Rapid Eye Movement) sleep. This significance
in children is not worked out.
Doxepin, nortriptyline These are the two sedating tricyclic
antidepressants that come in liquid form. They may cause
continued sedation the next day; they may also cause activation
because they increase Norepinepherine function.
Chlomipramine mirtazapine (Remeron), Fluvoximine- These
are most the sedating of the serotonergic reuptake antidepressants.
Mirtazapine- an antidepressant with several areas of therapeutic
activity. More sedating in lower doses than higher doses.
c) Standard Antipsychotics
Thioridazine (Mellaril) (Tablets, liquid, concentrate) Sedation is from
antihistamine properties; it may cause daytime sedation. This is a
typical antipsychotic with the various negative side effects. Use is
generally, but not always, reserved for individuals who have some psychotic-like
symptoms. Recently, it was given a caution label because of the infrequent
occurance of heart rate irregularity.
Loxapine ( Loxitane) A mildly sedating standard antipsychotic
with little anticholinergic side effects. Liquid is available.
Often useful to help psychotic dreams.
d) Atypical Antipsychotics. Clozapine and
olanzapine are most sedating, quetiapine is somewhat less.
Risperdone is the most activating but is sedating in a
few individuals.
e) Hypnotics.
Chloral Hydrate. An old fashion, short acting sleeping medication.
Available in liquid form. It may be more toxic than newer medications.
"Sleeping pills" The various benzodiazepine anti-anxiety
medications, when used as nighttime hypnotics have a reputation
for losing their effect over time and for causing paradoxical
arousal in children --especially those with Attention Deficit
Disorder. However, some autistic children have genuine
anxiety as a cause of their poor sleep and benefit from
long term use of this class which includes alprazolam,
(Xanax), lorazepam ( Ativan), temazepam (Restoril) , diazepam
(Valium), and clonazepam (Klonopin).
Zolpidim. (Ambien) and zaleplon (Sonata) are considered "better
sleeping pills” because they have a more selective action
than the above medications. They can be tried as an alternate
to the benzodiazepines. Of course, they are much more expensive. Sonata's
effect in the body is very short-lived.
f) Anticonvulsants
Valproic Acid or Depakote. This sedating anticonvulsant is often used
for sleep stability in adults with various brain dysfunction. Its
use in young children is extremely limited because of the potential
for liver toxicity.
Gabapentin (Neurontin) This may be a useful medication
for nighttime sedation and mood stabilization. It has already
developed some reputation for the treatment of the sleep
disorder, Restless Legs Syndrome.
g) Miscellaneous.
Melotonin. This health food product has some publicity on Autism web
pages.
Melotonin is not a "sleeping pill " but can help set regular sleep cycles
when taken regularly at the same time in the evening. Less than 1 mg
is often adequate, but it may be taken in doses up to 5 mg. There are
both regular and long-acting forms available. (One parent reported that
the form with added pyridoxine (B6) was less effective.)
B. Lowering the Immature Adrenaline Arousal of
the Body with "Anti-Adrenaline
Medications."
One very common dysfunction in the developmentally disabled is that of Adrenaline
overactivity. The way that adrenaline overactivity contributes to behavioral
difficulty has not been studied adequately by the general psychiatric community
in recent years. The process is very complicated. A brief outline of adrenaline
overarousal states and treatments is listed below.
1. Excess beta-adrenaline arousal. This is the typical mental
overarousal and physical hyperactivity seen in the juvenile. Signs of this
condition include fast heart rate (average 90 to 140/min), fine finger tremor,
picked or bitten finger nails, outbreaks of rage reaction (wild, unfocused). These
symptoms are not unusual in children, but their disinhibiting effects on
behavior are exaggerated in any child with a developmental disability. Treatment:
beta-blocking medications.
2. Excess mental adrenaline arousal. This is a standard feature of immaturity
but also may be part of the Attention Deficit Hyperactivity syndrome.
It may respond to use of clonidine or other alpha-2-agonist used in the daytime.
3. Panic or Fright Rage reaction. (beta-adrenergic crisis) This is
the wild, unfocused, panicky rage seen in individuals with fright and insecurity.
Treatment should include beta-blocking medications.
4. Psychotic rage reaction. (Alpha adrenergic crisis) This is
a very specific -- and more terrifying -- type of rage. The individuals have
the following symptoms. 1) Develop a weird, wild expression, 2) Become wild-eyed
with dilated pupils. 3) Act strangely, as if they don't recognize caregivers.
4) Make animal-like noises and swear. 5) Make deliberate attacks for the
face, throat or other venerable areas. 6) May not remember the event afterward.
7) Will have an elevated blood pressure - both top and bottom numbers. It
may also be called Predator Rage, Alpha-adrenergic Rage, Pathological Rage,
Criminal Rage, Amnestic Rage.Treatment should include Alpha-blocking
medications.
C. Attention Deficit Hyperactive Disorder (ADHD)
Everyone is aware of the use of psychostimulants to treat children with
Attention whatever Disorder. The practice of trying stimulants for every
problem behavior of childhood creates prejudice and misinformation about
this very important, specific disorder-which is the inability of the individual
to screen out external stimuli and internal thoughts in order to be able
to maintain mental focus. This problem can be reversed by stimulant medications
allowing for better behavioral control.
In general, use of psychostimulants has a bad reputation in
the Autistic population. Children with autistic symptoms have many reasons for
their lack of attention, but may have true Attention Deficit Disorder. Those
that have Attention Deficit Disorder can be helped considerably by use of Psychostimulants.
Give a low dose trial, starting the medication only in the morning. Move cautiously
higher till a positive or negative result is seen. Perhaps then add a second,
generally lower dose at the time the effect of the first dose is fading. But
note that it is the higher doses of stimulant medications given later in the
day that often create side effects such as irritability and psychosis. Do not
expect psychostimulants to do too much. At this time, I consider
that individuals with Autistic symptoms receiving psychostimulants as their only
medication are being inadequately treated.
Other medication treatment for Attention Deficit Disorder: There
are several antidepressant medications which have some ability to treat Attention
Deficit Disorder. Of these, buproprion (Wellbutrin), venlefaxine (Effexor), and
desipramine (Norpramin) are the most commonly used for this purpose.
D. Impulse Control Disorder (NOS) (Giddy Disinhibition Variety)
This is the clinical phenomenon in which the individual reacts to everything
in a non-serious, giddy way. Especially noted is the lack of a sense of concern
about approval of social authority. There may be a high tolerance for
physical pain, and deliberate seeking of pain --such as pinching fingers
in the cracks of closing doors. Highly autistic individuals are rarely seen
with this syndrome, but it is common in individuals with PDD who have some
autistic and obsessive-compulsive traits. The symptoms often improve
rapidly with use of the narcotic antagonist, naltrexone (ReVia*) using doses
of 1/2 to 1 mg per pound. This use for naltrexone is not found
in standard literature, but there are references in the literature about
the use of naltrexone to control self-injurious behavior and also for direct
benefit of autistic symptoms.
E. Anxiety.
If a hyperactive autistic individual does not have Attention Deficit Disorder,
one must seriously consider if there is treatable anxiety. Some individuals
have chronic anxiety or discreet panic attacks and are never treated well
because of the fear that giving a benzodiazepine antianxiety medication may
cause paradoxical reaction or addiction. For such individuals a trial of
low dose alprazolam (Xanax*) should be given. Start trial doses given before
a time when the anxious behavior may possibly occur. Start with a low dose
(0.125 or 0.25 mg) and use increasing doses up to 1 to 2 mg. Positive results
are a calming effect. Negative results are 1) paradoxical excitement. 2)
causing sleep but no calming when awake, 3) A sedated awake state with no
agitation ("agitated drunk"). If there is paradoxical excitement, consider
treating for Attention Deficit Disorder with stimulants. (Note that some
individuals will respond well to a single dose but become agitated after
several days of continued dosing on this class of medication.)
Buspirone (BuSpar*) This is a non-sedating anti-anxiety medication which
effects the serotonin system. It is sometime effective in lowering anxiety,
aggression, self-abuse, obsessive-compulsion and depression. It can be used
together with other serotonin medications and benzodiazepine anti-anxiety
medications. The dose of BuSpar is from 10 - 90 mg a day. Its treatment benefits
are slow to occur and difficult to assess. If one has the patience to find
a therapeutic dose, it sometimes is very beneficial. Besides side effects
of headache and gastrointestinal upset, its big problem is not knowing if
it is doing anything.
F. Mood Swings (Bipolar Disorder)
In adolescents and adults with Autism, there is a significant amount of Bipolar
Mood Swings. MOOD SWINGS are true changes
in body function systems such as sleep, appetite, and prolonged episodes
of manic or depressed mood which are not highly correlated to immediate
events. They are NOT minute by minute shifts in behavior from agitated to
calm!!! There is a tendency recently to overdiagnose Bipolar
Disorder in children with Pervasive Developmental Disorder (PDD) by physicians
who do not know how to treat Autistic withdraw, adrenergic disturbances,
and dissociative psychosis, but some individuals will never stabilize unless
they are on mood stabilizers. Therefore, mood stabilizers are often given "just
in case." The following rules are helpful but certainly not absolute.
1) Autistic children with seizures should always be on a mood-stabilizing
anticonvulsant. (Phenytoin= Dilantin*, Phenobarbital, Felbamate =Felbatol*
are not mood-stabilizing.)
2) Autistic children who have had epilepsy should not be given a trial discontinuation
of mood-stabilizing anti-convulsant unless there is psychiatric stability.
3) Autistic children who have a history of brain injury or abnormal EEG should
be considered for use of mood-stabilizing anticonvulsant.
4) Individuals who have a strong family history for Bipolar Disorder should
be considered for use of a mood-stabilizing medication. Perhaps using Lithium.
5) Lithium and valproic acid (Depakene* or Depakote*) frequently cause weight
gain with increased carbohydrate craving, This is especially a problem in
individuals with Obsessive-Compulsive Disorder.
6) Carbamezapine (Tegretol*) has proven mood-stabilizing properties and does
not cause increased appetite.
7) The anticonvulsants lamotrigine (Lamictal*), topiramate (Topamax*), and
gabapentin (Neurontin*) have demonstrated capacity for mood stabilization
but experience is limited.
8) Multiple mood-stabilizing medications must be used in some individuals.
9) Atypical Antipsychotics (especially clozapine) and the calcium channel
blocker nimodipine (Nimatop*) have demonstrated mood-stabilizing effects.
G. Treatment of Depression and Use of Antidepressants.
Many autistic individuals have Depression which responds to the various antidepressants.
Since antidepressants are also used for treatment of Obsessive Compulsive Disorder,
Attentions Deficit Disorder, and sleep disturbances, the choice of antidepressant
is often dictated by other symptoms.
H. "Dissociative" Aggression and Agitation.
This cause of aggression is poorly worked out and understood.
Unlike the "adrenergic" rages referred to previously, this type of aggressive
arousal is not necessarily related to signs of arousal in the body such as elevated
pulse and blood pressure. It is "sparked" by a “mental switch” which turns
on various brain arousal mechanisms. Caregivers often describe this as
a Jekyll and Hyde phenomenon where the person is suddenly a "different person." Sometimes
the changes may be truly dissociative in nature with memory loss. But more often
the individual simply acts like a “different person.”
The triggers for these changes may be the arousal mechanisms
of brain noradrenaline and brain dopamine neurons. Therefore, it is sometimes
useful to treat individuals who have such dissociative aggressive episodes with
medications that lower the quantity of chemicals that can be stored in the neurons. Two
such medicines, reserpine and Demser (metyrosine), are
not commonly used in psychiatry at this time, and only reserpine has ever been
used regularly.
III. COMPLEX MEDICATION REGIMES-MADISONDOCTRINE'S
VIEW
A. Questions
and Answers--Are Such Medication Regimes Safe for Use in Autistic
Individuals?
Why
use more than one medication at one time?
How many medications can be used?
What do all these medicines do to
the body?
It has already been stated that both the Atypical Antipsychotic and the
Selective Serotonin Reuptake Inhibitors have very specific and different
benefits to help the autistic-prone individual move out of his inner world.
The non-specific medications need to be used in whatever combination necessary
to provide as much stability in the wild shifts of behavioral reactivity
as possible. There is no such thing as a maximum number
of medications. This statement is counter to the standard philosophy
which states that medications should be given to treat specific psychiatric
diagnoses, and generally should be given one at a time to see if the symptoms
of the treated disorder improve. There will always be those physicians who
will contend that this is the only way one can “know what one is doing.” But
such treatment often does not do enough nor does it do it soon enough. Of
course, all medications have risks--some of them quite serious. However,
the present medications used for both specific and non-specific control of
symptoms are certainly less dangerous than allowing the affected individual
to continue the unrelenting natural course of Autism into an increasingly
unsocial behaviour pattern.
B. The Splint Concept of Medication Therapy (The Parable of the Badly
Fractured Leg)
Consider the case of an individual who was in a bad accident and sustained
five separate fractures of the right leg, which was also damaged in other
ways to make internal fixation impossible. The surgeon might devise a series
of splints, casts, and pin fixation systems to immobilize the leg and hold
it still while its various fractures heal inside. Might someone come along
and say, “Doctor Bones, you really should be using only five devices to stabilize
this leg not six, you need to take one off.” ? Surely, Dr. Bones would consider
some devices less important than others, but he would not want to take any
one away unless he saw it causing some particular problem -- because he would
be aware that the purpose of the treatment is to provide
stabilization that allows for permanent internal change.In the same
way the multiple medications proposed in this scheme are not designed to “cure” a
specific psychiatric illness, but rather to stabilize a disorganized, immature
nervous system and allow it to grow in a more balanced way. Stabilization
factors need not be medication -- various environmental manipulations, behavioral
training techniques, and specialized programs can contribute to the required
stability. However, medication offers round-the-clock help with benefits
that are not totally dependent on the stability of the social environment.
Medication has a constant influence that is impossible to match in even the
most rigorous behavioral training programs. Internalized autistic withdrawal
is so pervasive in its influence that all means possible need to be used
together to help an afflicted individual develop a more normalized life.
Belief that Autism can be treated adequately without the use medications
would seem to be a noble ideal, but is quite foolhardy -- and it denies the
autistic individual a chance for a more balanced life.
IV. "GATING," GLYCINE, AND THE
WAVE OF THE FUTURE?
A. Gating.
"Gating" is a term I am using to explain a long-acting effect from a short
acting treatment. There may be a more scientific term, but I have not
encountered it. Generally, treatment benefits last only as long as treatment
is given; however, in a "gating" situation, the improvement lasts much longer
than the actual treatment. I have termed this "gating" because the
results are like opening the gate to a field, allowing livestock to escape.
After the livestock have escaped, simply closing the gate does not force
them back into the pen. Over the years, there have been many stories of
autistic individuals who have suddenly displayed prolonged improvement
through the means of some particular behavioral treatment or medication.
The change in the individual is noted to be sudden, with a significant change
in communication and socialization often at a level much higher than demonstrated
previously–as if a gate had been opened..
1. Stories of sudden, prolonged improvement in certain
autistic individuals which I have encountered.
1) The well-publicized case of the Kauffmans from England who spent hours
sharing the world of autistic self-stimulation with their son. The
child suddenly became communicative, regressed, then recovered. (Refer
to their book, Son Rise-The Miracle Continues (1) ).
2) A case documented on film of a twenty year old blind man who had been
non-verbal for years, who was discovered at the piano playing and singing
songs. He went on to develop communicative speech.
3) There were stories of a very few autistic individuals becoming nearly
normal in their socialization after they learned how to communicate with
the facilitated communicator techniques that were used in the early 1990’s.
4) One of my very self-abusive autistic patients, who generally is constantly
needing restraints for her arms and very dangerous to herself until placed
on clozapine, once spent two days out of restraints in a happy social mood. She
then regressed to self-abuse and required restraints again.
5) The miraculous changes that occurred in some individuals that were treated
with Secretin. At first, they were given the Secretin for testing poor intestinal
function, but when their autistic symptoms improved so markedly, the practice
of giving Secretin for treatment of Autism developed. Sometimes Secretin
has been given intravenously and sometimes by a transdermal preparation prepared
by compounding pharmacists. Not many of those treated obtain the exceptional
benefits seen in the first cases reported.
2. "Gating" Phenomena as a Logical Conclusion
The MNDA glutamate/glycine, serine receptor complex seems to have an "anti-Autism" property
as well as a "gating" mechanism. Though too complicated for a full explanation
here, the MNDA receptor mechanism, which is a strong stimulant activator
for brain function, can be indirectly activated by the use of various chemicals
related to the naturally occurring amino acids, Glycine and Serine. There
are reports of improvement in negative symptoms in Schizophrenia after use
of Glycine/Serine medications. It is possible that the switching on of the
Glycine/MNDA receptor provides the mechanism for the "switching" between
the autistic brain function and the socialization brain function seen in
case of autistic individuals who demonstrate extraordinary improvement. MadisonDoctrine
started gaining experience with this potential treatment in the summer of
2000.
B. The Autism vs. Socialization Conflict is a standard part
of brain function.
There seems to be a mechanism in the brain that could explain the “gating” between
autistic activity and socialization/communication activity. The experience
that there are two opposing forces within the brain of the autistic individual–one
causing autistic behavior, the other socialization/communication behavior – leads
to a different answer to the frequently asked question “What causes Autism?” Rather
than viewing Autism as something that happens to the brains of individuals
who have autistic symptoms, it is better to view every brain as having an autistic
component and a non-autistic component. In most individuals, there is
a balance between these two components; so people are generally not “trapped” in
their internal autistic world. People with Autism have a barrier to free
external communication. The barrier may occur for any number of reasons:
genetic predisposition, psychological or physical injury, etc. Any particular
difficulty may be the “cause” of the Autism in a particular individual. However,
the actual cause of Autism is the very nature of the brain itself. All
brains have an autistic functioning unit and a non-autistic functioning unit
as part of their normal development.
1. The work of Margaret Mahler
The above statement seems to be validated by the work of a mid-20th century
child psychiatrist named Margaret Mahler. In her book, The Psychological
Birth of the Human Infant, she demonstrates that early in the development,
the child has two primitive personality states. The first is the autistic
self that lives within an internalized world blocking out external stimuli. "The
child with predominantly autistic defenses seems to treat the 'mother
in the flesh' as nonexistent." (2) The second is the symbiotic self,
a state in which a child is so enmeshed in reacting to external stimulation
that it may perceive that it is not a separate individual from its adult
caregiver. "On the other hand, the child with a predominantly symbiotic
organization seems to treat the mother as if she were part of the self,
that is, as not [being] separate from the self but rather fused
with it." (2) Dr. Mahler demonstrated the activity of these two “functioning
selves” in the course of development of normal children. It is
very easy to extend this concept to the extreme and believe that autistic
individuals become totally trapped in their autistic self and close down
most of the inter-personal dependency of the symbiotic function of their
brain.
2. The key to Autism will be finding the secret
of the "gate"
The concept that a hidden or dissociative self is significant in development
of the brain is an important feature of MadisonDoctrine’s understanding
of mental illness. In future descriptions of other disorders, this concept
will be expanded. In Autism, this dissociation allows for a “socialization
factor” to function in an autistic individuals even while they are living
in social withdrawal. Thus, it is possible for us to see the “miraculous” switches
from an autistic function to a more socialized function very quickly. There
is a strong possibility that the NMDA/glycine receptor mechanism is a key
to this switch. The various medication, nutritional, and behavioral techniques
which have produced an occasional positive result, may have been indirectly
effecting change at this receptor site. It is also possible that the NMDA/glycine
receptor mechanism is itself an indirect mechanism. This will be learned
over the next few years.
References:
(1) Son-Rise : The Miracle Continues. Barry
Neil Kaufman. H J Kramer 1995
(2) The Psychological Birth of the Human Infant. Margaret
S. Mahler et al. pp. 7. HarperCollins Publishers 1975
Appendix 1
Description and Differences Among the Various Atypical
Antipsychotics.
Web Memo 000818D
There are four on the market. They will be listed in order
of importance in use in young children.
1. Risperidone (Risperdal -Jansaan --1994) The most
activating and mood brightening.Often causes too much disinhibition
of the immature socialization drive. ( "Instead of flicking his fingers
in front of his own eyes, he keeps poking them in front of mine.") Keeping
doses low helps, but disinhibition is the major behavioral cause
of discontinuation. Physical side effects: Can causeParkinson-like
tremor and high prolactin levels (which are especially a problem
in early puberty in girls). Questionable long-term effects: liver
damage, Tardive Dyskinesia Starting dose 2-6 years is
0.0025 to .005 mg/day of syrup (1-2 drop = 1/40 to 1/20 ml.). 6-15
yrs. start 0.0125mg/ day. (1/8 of 1mg tab) [The most
accurate drops are obtained from an insulin syringe with the needle
broken off.]
2. Quiteipine (Seroquel) -Seneca -- 1997) Newest released
of this class.Definitely mood brightening like Risperdal but
not as activating. Infrequently causes movement and prolactin
side effects. It may well become the most useful medication for
use in non-psychotic states. It has a short half-life (2-4 hours)
and in some individuals it necessary to give on a twice-a-day
basis. Tablet size 25, 100, 200 mgs. (Not scored, but tablets
can be cut in half) 100 mg. of Seroquel is roughly
equivalent to 1 mg. of Risperdal.
3. Olanzepine (Zyprexa) (Lilly - 1996) Much less activating
than Risperdal and Seroquel. Quite sedating, may be the choice
for individuals with psychotic over-activation, however, there
have been more individuals developing agitation on Zyprexa than
expected. It has not replaced Clozaril as the "last resort" for
aggression. Tablet sizes- 2.5, 5.0, 7.5, 10 mgs. Tablets
can be divided into halves and quarters with pill cutter or exacto
knife. (This is against manufacturer's recommendations) It has
a long half-life in the body. One way to titrate small doses
is to skip a dose one out of two or three nights. Equivalency
to other drugs is difficult -- perhaps 15 mg. Zyprexa = 6 mg
Risperdal or roughly 2.5 mg Zyprexa = 1 mg Risperdal.
4. Clozapine (Clozaril) - Novartis 1990) (available in generic)
The first Atypical Antipsychotic -- known and used outside USA
since mid-1970's. Most able to reverse severe psychotic withdrawn
state of schizophrenia -- especially when accompanied by aggression.
Has significant side effects including 2% of less occurrence
of potentially lethal allergic reaction that destroys white blood
cells. This forces routine blood tests weekly or biweekly. Other
significant side effects include: Increased tendency for seizures, Sedation,
Excess salivation related to swallowing dysfunction, weight gain,
Constipation, Postural hypotension. It has been used in older
autistic individuals, but I have not seen it be as effective
in aggression in younger (10-15) Pervasive Development Disorder
children as various antiadrenergic and neurotransmitter depleter
medications. However, it is worth considering in some situations
-- for example, if a young autistic individual improved on the
other Atypical Antipsychotics but had excessive disinhibition. One
would then expect the dose of Clozapine to be in the 6.25 to
100 mg a day range for a young child. (100 mg. Clozaril
= 1 mg. Risperdal ?)
Appendix 2
Description and Differences
Among the Various Serotonin Re-uptake Antidepressants (SSRI's)
Madison Memo 000823D
Listed somewhat in descending
order of activation.
A) Fluoxetine (Prozac). (Capsules (20 and 10 mg, and liquid)
Exceptionally long lasting -- up to two week. Thus full effect of dosage
not seen for two plus weeks. Can give VERY low doses such as 4 mg two
time a week! Generally activating. Side effects: Insomnia, Diarrhea,
Nausea, Headache.
B) Sertraline (Zoloft) (Tablets 50, 100 mg.) Similar to Prozac
in activation. Perhaps causes more gastrointestinal side effects. Is
shorter acting, may not cause sleep disturbances when Prozac does.
C) Citralopram (Celexa-- 20-40 mg.) Not as activating as Prozac and
Zoloft, less sedating than Paxil. Has few drug-interactions.
D) Paroxetine (Paxil) (Tablets 10, 20, 30, 40mg and liquid) Not as activating
more sedating. Has some anticholinergic effect -- may have the least
tendency for intestinal upset.
E) Fluvoxamine (Luvox) Tablets 25, 50. 100 mg.) Least activating
and most sedating. Short acting and sometimes requires being given
2 x a day.
F) Chloripramine (Anafranil) (Caps 25, 50 mg- (10 mg. tab. Canada) The
first medication to treat Obsessive-compulsive disorder. This is a tricyclic
antidepressant with all the typical side effects. (Sedation, increased
tendency for seizures, constipation, dry mouth, low blood pressure on
standing.) Chloripramine is sometimes the only medication that some individuals
can tolerate. (Smaller doses can be made mixing the contents of the capsule
in honey-- a real nuisance. Compounding pharmacies can make liquid preparation
or 10 mg. Capsules)
The aim of therapy is to start with low doses of the medication most
likely to be tolerated and to raise slowly. If side effect occur, a different
medication can be added or used as a replacement.
There are individuals who cannot tolerate any of the above medications.
Sometimes compulsive symptoms are somewhat relieved with other serotonergic
medications such as Buspirone, Trazadone, Nefazadone
Appendix 3
Alpha-2-Agonists
Clonidine- (Catapres- Ingerheim-Boehringer) [Generic-yes] 0.1,
0.2, 0.3 mg tab and skin patches) The most well known. Wide range of
dosage from 0.0125 mg in children to 0.6 mg/ dose in some adults. Tasteless,
it can be dissolved in mouth, or crushed and given with food; tablets
are even effective when given rectally. Rapid acting, it lasts 3 to 6
hours. Often helps hyperalert children go to sleep, but they may awaken
in the middle of the night with a rebound. A middle of the night
dose can be given. (Most generic brands cannot be broken into 1/4
size. The tablet by the Schein Co. can be, as can the trade brand Catapres.)
Catapres patch delivers the stated dose over 24 hour (e.g. a 0.2
patch would equal giving 0.05 mg every 6 hours. They last from 5 to 7
days, are reasonably waterproof. 20% of individuals develop intolerable
skin irritation. (The most inaccessible position on children is between
the shoulder blades.) The patch can be cut in pieces to produce intermediate
strengths—this is against the manufacturer’s recommendation.)
Clonidine (long acting capsules) can be made in various strengths by
compounding pharmacists—most frequently ones schooled in Texas.
These last about 12 hours. Insurance programs will not pay for them.
Guanfacine (Tenex )(1mg, 2mg) (generic-yes) A long-acting medication
which will last through the night, but may not be as effective as clonidine.
(The brand name 1 mg. tablet easily cuts into 1/4 or 1/8.)
Notes about Alpha-2-Agonists and sleep.
1. Some individual will go to sleep with clonidine then wake up on 4-6 hours
with a rebound over-alertness. A second dose of clonidine may be given.
2. Some individuals are paradoxically stimulated with these medications - they
do not achieve the preferential stimulation to the suppression side of the
Noradrenaline nerve connection.
3. Tenex and the Catapres patch will have effects through the day. Sometimes
this causes unacceptable lethargy, sometimes this produces the benefit of lowering
hyperactivity.
4. Sometimes giving a dose of regular clonidine at night to someone also taking
the longer-acting alpha-2-agonists will provide for regular sleep time and
prolonged sleep through the night.
5. As sleep patterns stabilize, some individuals will then take clonidine only
on nights when arousal prevents going to sleep.
Apendix 4
The Neurotransmitter
Depleting Medications.
Web Note 000822A
There are three available for use. They are most useful in those individuals
who have excessive activity and thus will not become depressed
by the loss of brain neurochemicals. Some individuals who seem to "get
lost in an autistic psychotic world" are not helped until they are placed
on this class of medications.
1. Reserpine. (No current trade brand – formerly Serpasil) An old medication
used to treat hypertension and psychosis. It causes Serotonin, Noradrenaline,
and Dopamine-containing nerve cells to lose some of their ability to store
their neurochemicals. (In general, its action affecting Serotonin is
unwanted.) There is the potential for movement side effects. Dosage size
0.1 and 0.25. Daily dosage 0.1 to 1.0 mg./day. Sometimes a low
dose of reserpine can make a marked difference in the antisocial aggressive
activities of some individuals with dissociative aggression.
2. Demser (metyrosine - Merck) Marketed for
the treatment of adrenal gland tumors. It blocks the synthesis of
Dopamine and Norepinepherine. It is most useful for dissociative
aggression with psychotic features. Wholesale drug houses do
NOT stock Demser. Pharmacies must order directly from the manufacturer,
Merck, where orders can be made by calling (800) 637-2579, or have
the wholesale house order for individual patients. There is the potential
for significant movement side effects--including Neuroleptic Malignant
Syndrome. Available in 250 mg capsules which can be opened and mixed
with liquids. Daily dosage 250 mg to 2000 mg./day.
3. Aldomet (methyldopa) It is marketed for lowering
blood pressure. It blocks the synthesis of Norepinepherine but not
Dopamine. Is free of movement side effects. Available in 500,
250 mg tablets and liquid. Dosage range - 150 mg to 3000 mg
a day. There is the possibility of a supersensitivity reaction
which can cause a hemolytic anemia. It is recommended that
a direct Coombs test and CBC be done routinely every three months
for the first year. This medication seems to have the advantage in
those individuals whose behaviors seem mostly to have physical agitation
without psychosis but who do not have the constant state of adrenaline
arousal that might respond to the adrenaline blocking medications
and Alpha-2-agonists.
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