DRUG INDEX

• Summary: Ritalin / Methyl Phenidate is a PRESCRIPTION ONLY drug for helping patients with a number of mental disorders like hyper-activity, attention-deficit disorders, autism, etc. It is included here only for guidance about what to tell your doctor, and NOT FOR SELF MEDICATION

  Description

  Methylphenidate (meth-ill-FEN-i-date) belongs to the group of medicines called central stimulants. It is used to treat Attention-Deficit Hyperactivity Disorder (ADHD).

  Methylphenidate works by increasing attention and decreasing restlessness in children and adults who are overactive, cannot concentrate for very long or are easily distracted, and are impulsive. This medicine is used as part of a total treatment program that also includes social, educational, and psychological treatment.

  Methylphenidate is also used in the treatment of narcolepsy (uncontrollable desire for sleep or sudden attacks of deep sleep).

  This medicine is available only with a doctor’s prescription. Prescriptions cannot be refilled. A new written prescription must be obtained from your doctor each time you or your child needs this medicine.

  Methylphenidate is available in the following dosage forms:

  • Oral
  • Tablets
  • Extended-release tablets

  Proper Use of This Medicine

  • Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming.
  • Take this medicine with or after meals or a snack.
  • To help prevent trouble in sleeping, take the last dose of the short-acting tablets before 6 p.m., unless otherwise directed by your doctor.
  • If you think this medicine is not working properly after you have taken it for several weeks, do not increase the dose. Instead, check with your doctor.

  If you are taking the long-acting form of this medicine:

  • These tablets are to be swallowed whole. Do not break, crush, or chew before swallowing.

  Dosing

  The dose of methylphenidate will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of methylphenidate. If your dose is different, do not change it unless your doctor tells you to do so.

  The number of tablets that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using methylphenidate.

  For attention-deficit hyperactivity disorder:

  For short-acting oral dosage form (tablets):

  • Adults and teenagers—5 to 20 milligrams (mg) two or three times a day, taken with or after meals.
  • Children 6 years of age and over—To start, 5 mg two times a day, taken with or after breakfast and lunch. Your doctor may increase the dose if needed by 5 to 10 mg a week until symptoms improve or a maximum dose is reached.
  • Children up to 6 years of age—The dose must be determined by the doctor.

  For long-acting oral dosage form (extended-release tablets):

  • Adults and teenagers—20 mg one to three times a day, spaced eight hours apart.
  • Children 6 years of age and over—20 mg one to three times a day, spaced eight hours apart.
  • Children up to 6 years of age—The dose must be determined by the doctor.

  For narcolepsy:

  For short-acting oral dosage form (tablets):

  • Adults and teenagers—5 to 20 mg two or three times a day, taken with or after meals.

  For long-acting oral dosage form (extended-release tablets):

  • Adults and teenagers—20 mg one to three times a day, spaced eight hours apart.
  • Missed dose—If you miss a dose of this medicine, take it as soon as possible. Then take any remaining doses for that day at regularly spaced intervals. Do not double doses.

  Storage—To store this medicine:

  • Keep out of the reach of children.
  • Store away from heat and direct light.
  • Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
  • Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

  Side Effects of This Medicine

  Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

  Check with your doctor as soon as possible if any of the following side effects occur:

  • More common
    • Fast heartbeat; increased blood pressure
  • Less common
    • Black, tarry stools; blood in urine or stools; chest pain; fever; joint pain; pinpoint red spots on skin; skin rash or hives; uncontrolled movements of the body; unusual bleeding or bruising
  • Rare
    • Blurred vision or any change in vision; uncontrolled vocal outbursts and tics (uncontrolled and repeated body movements)
  • With long-term use or at high doses
    • Mood or mental changes; weight loss
  • Symptoms of overdose
  • Agitation; confusion (severe); convulsions (seizures); dryness of mouth or mucous membranes; false sense of well-being; fast, pounding, or irregular heartbeat; fever; headache (severe); increased blood pressure; increased sweating; large pupils; muscle twitching; overactive reflexes; seeing, hearing, or feeling things that are not there; trembling or tremors; vomiting
  • Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:
    • More common
      • Loss of appetite; nervousness; trouble in sleeping
    • Less common
      • Dizziness; drowsiness; headache; nausea; stomach pain

  After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you were using and how long you used it. During this period of time check with your doctor if you notice any of the following side effects:

  • Mental depression (severe); unusual behavior; unusual tiredness or weakness
  • Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor

  Acknowledgement: This text is based upon the matter given in USP DI® and is only meant as a guide, with no commercial interest.

Summary: Melatonin is a natural hormone, synthesized and released by the pineal gland at the base of the brain, in a cyclical manner, to regulate our inbuilt biological clock. This induces sleep, hunger, etc. at set times, to regulate our body functions.

Background to Melatonin

The human body has a built in biological clock that runs on a 25 hour cycle, not the 24 hour cycle that the sun has. To correct this anomaly, the brain has a clock regulator called melatonin, a hormone secreted by a tiny gland situated at the base of the brain called pineal gland. The gland is closely associated with the pathway of nerves and neurons between the eyes and the visual centers in brain. The release of the melatonin hormone from the gland is signaled by the absence of signals from the eye to the brain, i.e. the sense of darkness. The resultant higher levels of the hormone in blood inhibit the centers in the brain stem responsible for keeping us awake, thus inducing sleep

This hormone has long remained a mystery, and still is. We know only sketchy details about its role in the human system. It helps the body to synchronize itself with the solar day, regulate when we sleep, eat, work as well as when most other hormones should or should not be secreted. For example, the level of the stress hormone, hydrocortisone, peaks at mid-day and troughs at midnight. Corresponding to this, asthma attacks are least common at day and come with increased frequency and severity at night. This is a simple example of how melatonin may regulate the body. In totality, the actual effects of melatonin have much wider application.

Melatonin is so safe that it is permitted for sale over the counter without prescription, for sleep disturbances, especially for those due to Jet-lag after prolonged international travel, night duty work hours, etc.. It is usually given about half an hour before going to bed. The bedroom should be quite and dark for optimum effect. The usual dose is one to three tablets of 3 mg. each, given as a single pre-bedtime dose, though doses many folds higher have shown no ill effects. In case tolerance develops over time, it’s use should be stopped for two to four weeks to allow the body to overcome the tolerance and regain efficacy. It’s dose must not be increased to overcome tolerance.

Melatonin in Autism

Now, evidence is beginning to emerge that melatonin may also influence behavior in autism, as per an article by Jaak Panksepp, Ph.D. Bowling Green State University Bowling Green, OH

Autistic children often have sleep disturbances, which suggests that there may be some problem associated with the melatonin system. Melatonin seems to be an effective sleep regulator, not only for autistic children but also indirectly for their overworked parents. Autistic children receiving melatonin regularly exhibit benefits that cannot be explained in simple terms like better sleep. It may be a combination of better sleep, better control of biological rhythms and high Anti-Oxidant effect.

[During various body chemical reactions, many harmful ionized particles are liberated called FREE RADICALS. They try to burn adjacent body tissues and chemicals, and have been implicated as the cause of old age degenerations, hypertension, atherosclerosis, cataract, macular degeneration of eyes, and so on. Agents that neutralize these ionized particles before they can cause harm are called Anti-Oxidants, and include vitamin E, vitamin C, carotenoids in vegetables and fruits, as well as many body-generated chemicals. Melatonin is an extremely powerful Anti-Oxidant surpassing vitamin E or C.]

Melatonin therapy of Autism certainly merits more research. However, there appears to be no harm in giving it to sleep deprived autistic children / persons, as it appears to be safe, effective, and possible useful. If they sleep well, their parents or care-givers sleep well too. However, it is necessary to do so, especially in children, only under the supervision of the regular physician, till we have more data.

Mercury Vaccine:

Outraged by the Institute of Medicine’s (IOM) latest report finding no causal relationship to thimerosal, a mercury based preservative, and autism, Congress Members, Doctors, and Scientists speak out about its conflicts of interest and conclusions based on flawed studies:

Washington D.C. – In light of the recent Institute of medicine’s (IOM) latest report citing “…rejection of a causal relationship between thimerosal containing vaccines and autism,” Congress Members along with doctors and scientists speak out about how the IOM came to their questionable conclusion.

“The report released from the IOM clearly indicates the complete absence of any desire to discover scientific truth at the supposed highest levels of medical academia. The individuals responsible for the IOM report either severely lack any intellectual integrity or, are suffering from neurological impairment due to mercury toxicity themselves. There is NO other explanation for the IOM report,” states Dr. Rashid Buttar.

Dr. Buttar recently gave Congressional testimony at a hearing with the Government Reform & Oversight Hearing Subcommittee on Wellness & Human Rights, on his revolutionary new treatment for autistic children that is getting them well by removing the mercury from their bodies. His son Abi has had a full recovery from his treatment.

“When 31 children recover from a devastating disease by a simple transdermal treatment that detoxifies metals, then common sense dictates that perhaps metals are involved,” states Dr. Bob Nash the chairman of the American Board of Clinical Metal Toxicology (ABCMT) in regard to Dr. Buttar’s treatment.

He adds, “Congress must create a National Metals Task Force by line item funding. This task force could be a resource to the congress and also establish a Quick Reaction Capability that presently does not exist to address health problems. We can no longer continue to destroy our children’s health even as an unintended consequence of a program that meant well. We need action today, not in 5 years.”

It appears the IOM based most of their findings on a Danish study by Anders Peter Hviid. Mr. Hviid clearly stated that from four months up to nine months of age, the discrepancy widens between the Danish and the US schedule showing clearly that American children have a much higher mercury burden than children in Denmark.

Another flawed study the IOM has seemed to base their findings on was by Elizabeth Miller of the UK. Ms. Miller stated that the children of the UK do not get the flu shot nor the hepatitis B shot as American children do. She goes on to add, “the only source of exposure to thimerosal containing vaccines in the UK children in the first year of life is the DTP or DT containing vaccines.” Which yet again reiterates that the American vaccine schedule clearly exposes children to a much higher amount of mercury containing vaccines in the first year of life.

Dr. Boyd Haley, while questioning Mr. Hviid’s findings asked him the rate of autism per 10,000 population in Denmark versus the US and Britain because he was showing two different vaccine schedules, Mr. Hviid was not able to give him an answer.

“The reason I asked the young man the question, our work is comparing apples to cows when we compare the American autism situation to the Danish situation,” says Dr. Haley.

He also points out, “So the conclusion that I have is, there appears to be a subset of the population that cannot effectively excrete mercury and they are at greater risk for exposure in the general population. The presence of the other heavy metals, antibiotics, may enhance the toxicity of thimerosal.”

Dr. Mark Geier comments on their studies, “At the high levels (of thimerosal exposure), it is undeniable there is a causal relationship, and we have gone to high levels. Their studies, therefore are not relevant, I am not saying they are wrong, although there are many criticisms of it. It is just not relative to the US situation.”

Dr. Geier’s study published in the peer-reviewed Journal of American Physicians and Surgeons concludes that there is an increase of neurodevelopment disorders following the use of Thimerosal containing vaccines

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Congressman Dave Weldon who opened the IOM meeting on Vaccine Safety and Autism, said, “Lastly, I am also troubled by the lack of liability or accountability by these decision makers should they be proved wrong. I want more than just a “sorry” from them should their conclusions be found erroneous a few years down the road. Too many lives are at stake.”

Autism Spectrum Disorders: An Update of Federal Government Initiatives and Revolutionary New Treatments of Neurodevelopmental Diseases

Opening Statement of Chairman Dan Burton

The Subcommittee is convening today to examine the advances in Federal Government initiatives, as well as new treatments that have been shown to benefit the medical condition of individuals afflicted with an Autism Spectrum Disorder.

As many of us already know, the incidences of autism have become increasingly prevalent in modern-day society. Once considered a rare disease, effecting roughly 1 in 10,000 children, autism now affects 1.5 Million of our Nation’s children, and this problem continues to escalate rapidly.

According to a recent “Autism Alarm” released by the U.S. Department of Health and Human Services (HHS), the Centres for Disease Control (CDC), and the American Academy of Paediatrics, currently 1 out of every 6 children are diagnosed with a developmental disorder and / or behavioural problem. Even more alarming, today 1 out of every 166 children in the United States is being diagnosed with an Autism Spectrum Disorder. This major healthcare crisis is clearly reaching epidemic proportions, and will not just simply “go away.”

As such, the United States government has rightfully begun to acknowledge the present and future public health implications of this autism epidemic by establishing an Interagency Autism Coordinating Committee (IACC). The IACC is comprised of representatives from HHS, the National Institutes of Health, the Department of Education, as well as various non-governmental organizations and parental support groups.

The IACC meets on a bi-annual basis to discuss and coordinate the various research projects with regard to autism, as well as to keep an open dialogue in addressing the numerous healthcare and educational needs of individuals with autism.

To further address the concerns of the autism community, HHS and the Department of Education at long last sponsored the first-ever “National Autism Summit” in November 2003. Some of the best scientific and medical researchers, as well as autism activists, key Members of Congress, and a host of parental support groups initiated an open dialogue on the status of research initiatives.

This summit was essential to bridging the relationship between the government, non-governmental organizations, and private citizens.

To better explain the status of Federal Government autism initiatives, the Subcommittee has the pleasure of hearing testimony today from the Honourable Troy Justesen (Justice – son), the Acting Assistant Secretary in the Office of Special Education and Rehabilitative Services, at the U.S. Department of Education.

During my tenure as the Chairman of the Full Committee on Government Reform, and as the current Chair of this Subcommittee, I have convened 20 hearings on the topics of Autism, vaccine safety, and the detrimental health effects of Mercury-containing medical products.

During these investigations, numerous scientists from around the globe have testified before the Committee and have presented credible peer-reviewed research studies that indicated a direct link between the exposure of Mercury, a widely known neurotoxin, and the increasing incidences of autism.

Because autistic individuals typically have a high concentration of Mercury stored in their bodies, many doctors are concerned with how exactly they can safely remove these toxins from their patients, without exposing them to greater medical risks.

One popular method to remove this poisonous metal, called chelation therapy, involves an intravenous solution that disperses and collects Mercury, ultimately to be flushed out of the body. Unfortunately, because of the way in which this therapy is administered, it is not recommended for use in children. Dr. Rashid Buttar (Rah-sheed, Boot-tar), has developed a groundbreaking transdermal chelator that has proven safe to use in treating paediatric patients. Dr. Buttar is testifying before the Subcommittee today to speak on his personal success and application of this groundbreaking treatment.

Another cutting edge medical development currently being tested for use in autistic patients is Hyperbaric Oxygen Therapy. This treatment, which involves the delivery of pressurized oxygen to a patient, has been recently used to assist with the regeneration of neurons in brain-injured individuals. Dr. Paul Harch, President of the International Hyperbaric Medical Association, will discuss how the use of Hyperbarics may be a viable therapy to administer to persons afflicted with an autism spectrum disorder.

In addition, Dr. Ken Stoller (Stole-er), has been invited to further supplement the testimony of Dr. Harch and discuss additional uses for Hyperbaric treatments for patients afflicted with other Neurodevelopmental diseases and injuries.

Finally, to gain the perspective of parents of brain-injured children, Ms. Julie Gordon, Founder and Director of MUMS (Mothers United for Moral Support), will be testifying today in regard to how coalitions of parents have come together and effectively lobbied for the advancement of their children’s health.

As I stated before, autism is an epidemic that directly affects millions of Americans, including every single taxpayer in the United States. I am pleased to see that our Nation’s health and education agencies are beginning to do their part to address this pandemic situation, and I implore them to continue their fight against these devastating diseases.

I would like to thank all of our witnesses for making the long trip to Washington for this most important hearing, and I look forward to hearing about the revolutionary treatments and current research that will hopefully one day completely eradicate these spectrum disorders.

Autism, The Misdiagnosis of Our Future Generations

US Congressional Sub-Committee Hearing

Over the last 15 years, the incidence of Autism has rapidly increased in the industrialized nations with the United States and the United Kingdom having the sharpest rise. A lot of the attention has been given regarding the link between mercury and autism, with mercury being the possible factor underlying the etiology of this condition. The issue of whether mercury plays a role in Autism or other Neurodevelopmental disorders has been the subject of long debate and extreme political discourse but the evidence is overwhelmingly obvious to even the simplest of intellects once the data is objectively reviewed.

The prevalence of mercury in our society is endemic in nature. The association of mercury with chronic disease in the US “medical literature” exists but is very anemic. However, when searching under Toxline under the ATSDR (Agency of Toxic Substances and Disease Registry), a division of CDC, one finds all scientific literature which also includes didactic literature, NOT just the “medical literature”. Not surprisingly to advanced researchers and physicians, the association of mercury to chronic diseases is well documented in the didactic scientific literature.

The search for the association between mercury and cardiovascular disease, the number one killer in the industrialized world, revealed 358 scientific papers exemplifying the relationship. The search for the association between mercury and cancer, the number two killer in the industrialized world, revealed 643 scientific papers exemplifying the relationship. Both of these conditions represent 80% cause of all deaths in the industrialized world, according to the WHO (World Health Organization) as published in 1998. But the association of mercury with neurodegenerative diseases is the most significant, with the references numbering 1445.

The inevitable question is how do we get exposed to mercury? The sources surround us, from mercury amalgams in our teeth, to the contamination of our water sources, inhalation of combustion from fossil fuel, fish that we consume, virtually all vaccinations, and via breast milk, just to name a few. So if mercury is so devastating, why is it allowed to be in our flu shots, vaccines, foods, etc.? This is the “million dollar” question, although it should be evident to the well informed the answer will be somewhere along the money trail.

Increased exposure to mercury through thimerosal containing vaccines is one of the most important issues at hand. Thimerosal (also known as Marthiolate) is the common name of a substance known as ethyl mercurithiosalicylic acid. The overburdening knowledge that thimerosal is converted to ethyl mercury (a substance over a thousand times more destructive than inorganic mercury) in less than one minute after being introduced into the body should give great concern to those appointed to protect the public. Yet, it is virtually ignored. Why is this highly toxic substance still allowed to be a constituent of our vaccines used to inoculate our precious children, our own future generations?

For example, the MSDS on thimerosal from Eli Lilly, documented on their own letter head as far back as July 13, 1991 clearly states that thimerosal is a “product containing a chemical known to the State of California to cause birth defects or other reproductive harm”. Yet Eli Lilly continues to use thimerosal in the manufacturing process for vaccines. However, the vaccine issue must not overshadow the cumulative mercury exposure experienced by the patient during gestation and early infancy. These additional exposures besides the vaccine history include dietary mercury content, dental amalgam fillings which contribute greatly to the maternal mercury load, Rhogam (immunoglobulin) administration to mother during gestation, exposure to combustion of fossil fuels, water contamination, and mercuric compounds used in skin products.

Mercury’s causes damage by various mechanisms which include: competitive and non-competitive inhibition of enzyme activity by reversibly or irreversibly binding to active sulfur, binding at the sites off and displacing other divalent cations, like magnesium, zinc, copper, and manganese causing a disruption of enzyme systems, disrupting critical electron transfer reactions, and complexing molecules and inducing a change in structure or conformation which causes them to be perceived as foreign by the body’s immune defence and repair system (hapten reactions) resulting in hypersensitivity that can potentiate or exacerbate autoimmune reactions. Mercury alters biological systems because of its affinity for sulfhydryl groups which are functional parts of most enzymes and hormones. Tissues with the highest concentrations of sulfhydryl groups include the brain, nerve tissue, spinal ganglia, anterior pituitary, adrenal medulla, liver, kidney, spleen, lungs heart and intestinal lymph glands.

But most relevant to us for the purposes of this hearing is that mercury has clearly been shown to causes a denudation of the neurofibrils resulting in direct damage to the neuronal cells. In addition, mercury exposure leads to many secondary clinical problems resulting from the aforementioned mechanisms of damage, such as immuno-suppression, allowing for opportunistic infections, allergies, GI dysbiosis, etc. Addressing all other issues in children with Autism is analogous to attempting to put out fires without addressing the cause of the fire itself. The fire will keep re-igniting unless the “spark” is eliminated. It is the elimination of this “spark”, i.e. mercury, for which we now have an easy and effective solution. Along with some supportive therapies, Autism and certain other chronic neurodegenerative diseases such as Alzheimer’s can be fully and permanently reversed if appropriately treated. This is NOT theory. It has already been clinically validated on a repetitive basis.

But first, let us answer the question why some people are affected while others show no manifestations of mercury toxicity, despite living in the same environments. In our case, the discussion will be limited to mercury, which is considered to be the second most toxic metal known to man but this explanation is applicable to most other heavy metals as well. Most individuals exposed to mercury as well as other heavy metals, have the ability to at least begin the process of eliminating these heavy metal out of their system. But not everyone has this ability and the extent of variability in the ability of an individual to detoxify their systems will determine the severity of the symptoms of toxicity. Slides #10 to #14 show the typical individual who can get rid of mercury with appropriate treatments.

Despite having been exposed to severe levels of mercury vapour, this patient named Robin T. was able to detoxify once appropriately treated with DMPS. Her mercury level was almost 22 fold greater or 2200% more than what is considered to be safe but with appropriate treatments, her levels returned to normal and her symptoms of mercury toxicity resolved. However, patients with impaired detoxification pathways do not show similar results on testing. Their bodies are unable to release the mercury and/or other metals and on testing, the mercury does not appear. The basis of our treatment protocol for children diagnosed with autism was determined by my clinical observation that certain individuals were unable to detoxify mercury like the vast majority of people appear to have the ability to do so. Slides #16 to # 21 show the case of Karen D. who showed no appreciable levels of mercury despite appropriately being “challenged” with DMPS by two different physicians over a year apart. But in Karen D.’s case, she could not detoxify her system effectively despite being treated appropriately with the correct diagnostic methods.

In Karen D’s case, she needed to have persistent treatment for a period of almost 2 years, as seen on slides #16 to #21 but as you will notice, her mercury levels continued to exponentially RISE until her last test which shows the results dramatically drop. What is most interesting is that as the test results revealed an increase in the mercury levels, the patient dramatically began to improve clinically. The reason the levels of mercury actually rose in each subsequent test, is that this testing method only determines how MUCH mercury and/or other metals we are able to remove. As treatment continued, we were effectively able to remove a greater quantity of mercury during each and every treatment.

It is important to note that this patient received treatments every week but the test results were obtained only every 20 weeks. Despite this disparity between treatments and testing, we see a dramatic and steady increase in mercury levels on testing, directly correlated with significant improvements clinically and alleviations of symptoms. In this particular patient, the symptoms for which she presented included galactorrhea, ataxia, dysphagia, inability to articulate with a new onset of stuttering, arrhythmia, chest pain, myalgias, arthralgias, hirsutism, cephalgia, insomnia, fatigue, malaise, depression, and anxiety. On presentation, the patient had notified me she had seen 16 other physicians in the previous 5 years and if I could NOT help her, she would “take care” of the problems herself because she could no longer live this way. This patient, Karen D. was 34 years old when she presented to me.

The level of mercury measured during each of Karen D.’s tests was inversely proportionate to the amount of mercury remaining in her system. The answer to the question of why some people are able to effectively release mercury and/or show absolutely no manifestations of mercury toxicity despite having lived in the same exact environments and had the same level of exposure to metals while others are severely affected with serious clinical manifestations, is not as difficult to answer as one would initially believe when the multiple variables are considered, which include the type of exposure, biological individuality and genetic predisposition. Drs. Michael Godfrey, et al, reported one such variable explaining the variability of individuals in detoxifying mercury in a landmark paper published in the Journal of Alzheimer’s Disease in 2003, entitle “Apolipoprotein E Genotyping as a Potential Biomarker for Mercury Neurotoxicity”.

Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon 4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer’s disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E e 4 groups was found in the patients (…0 001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3, dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.

We started treating children with Autism first in 1996. By 1997, we were being referred patients by a paediatric neurologist, who was following a mutual patient and observed significant changes in the child’s behavior after implementation of our treatments.

However, by the end of 1998, taking care of children with special needs proved more than I wanted to handle. Although we had far better success than the traditional approach, our treatments had not been responsible for “normalizing” any children. The emotional component was also overwhelming, just having to deal with the pain and frustration of the parents of these children. As a result, we stopped accepting new patients with the diagnosis of Autism or any type of developmental delay in early 1999.

On January 25, 1999, my son Abid Azam Ali Buttar was born. By the time he was 15 months old, he was saying “Abu” which means father in Arabic, and a few other words such as “bye bye”. But by the age of 18 months, my son had not only failed to progress in his ability to speak, but had also lost the few words he had been saying. At the age of 36 months, he had absolutely no verbal communication except for the one syllable that he would utter, “deh”, on a repetitive basis. As he grew older, I began to worry more and more than he was suffering from a developmental delay. He exhibited the same characteristics that so many parents with children that have developmental delays have observed, such as stemming, walking on tip toes, and lack of eye contact. Sometimes I would call to him but his lack of response would convince me there must be something wrong with his hearing. Certain sounds would make him cringe and he would put his hands on his ears to block the obvious discomfort he was experiencing. He would spend hours watching the oscillation of a fan. But through all this, when he would make eye contact with me, his eyes would say, “I know you can do it Dad”. The expression he would give me, for just an instant, would be that of a father encouraging his son.

The oceans of tears that I cried and the hours that I spent trying to figure out what was happening to my son are no different than that of any other parent in the same situation. The only difference was that I was one of only a 190 doctors through out the US board certified in clinical metal toxicology. And if this was metal related, I should know how to fix this problem. I tested him and re-tested him and tested him again, searching for mercury.

Slides # 23 to 27 show the results of my son’s test and how his system showed no appreciable levels of mercury. But the older he became, the more obvious it became that my son was not developing as he was meant to be developing. My son was not meant to be this way and that was the only one thing that I knew for certain.

About the same time while desperately searching for the cause of the same ailment that had afflicted so many of my own patients previously, I had been invited to present a lecture regarding some of our research on IGF-1 and the correlation with cancer. I had notified the conference that I was too busy to present this lecture but when I learned that Dr. Boyd Haley was also scheduled to present at this conference, I changed my schedule and agreed to lecture just so I could meet and discuss my son’s situation with Dr. Haley. That meeting turned out to be one of the key elements which resulted in our development and subsequent current protocol for treating children with autism, autism like spectrum and pervasive developmental delay. My son was the first one who went through this protocol once safety had been established. Dr. Haley told me of a study that had at the time, not yet been published

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Just before the turn of the century, Holmes, Blaxill and Haley did a study assessing the level of mercury measured in the hair of 45 normally developing children versus 94 children with Neurodevelopmental delays diagnosed as Autism using DSM IV criteria. The finding showed that the Autistic children had 0.47 parts per million of mercury in their hair where as the normally developing children had 3.63 parts per million, more than 7 times the same level of mercury as the Autistic children.

Opponents of the mercury-neurodegeneration camp used this opportunity to state that this study clearly showed that mercury had NOTHING to do with Autism or any other neurodegenerative condition.

However, they completely missed the point of the study. For the reader, the conclusion of the study is obvious, and in part, is reproduced below.

“The reduced levels of mercury in the first baby haircut of autistic infants raise clear questions about the detoxification capacity of a subset of infants. Despite hair levels suggesting low exposure, these infants had measured exposures at least equal to control population, suggesting that control infants were able eliminate mercury more effectively. In the case of autistic infants, those in our sample were exposed to higher levels of mercury during gestation, through dental amalgams or Rho D immunoglobulin injections in the mother. The addition of multiple postnatal exposures to mercury in childhood vaccines would have more severe consequences in infants whose detoxification capacity is reduced or who may be closer to a dangerous threshold exposure. In the case of control infants, mercury hair levels were strongly affected by exposure levels, suggesting that detoxification and excretion played an important role in ensuring normal development in children with elevate toxic exposure relative to peers. If reduced overall mercury elimination is related to hair elimination, then autistic infants will retain significantly higher levels of mercury in tissue, including the brain, than normal infants. In light of the biological plausibility of mercury’s role in Neurodevelopmental disorders, our study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.”

These findings were published in the International Journal of Toxicology in 2003.

Understanding these findings, along with my clinical experience with the case of Karen D. as previously detailed, led me to the conclusion that a more aggressive method of treatment was necessary compared to the DMSA and various other treatments I had to date employed in the attempt to document high levels of mercury in my son, which up to this point, had not been successful. The first two attempts with DMPS as a challenge treatment were unsuccessful, the first due to difficulty catching the urine since Abie was only 2 years old at the time, and the other due to loss of the urine specimen while being delivered to the laboratory. The third try with DMPS, which represented the 6th test we did on my son with all previous tests showing no appreciable levels of mercury, resulted in the findings on slide #29, the results that were reported to me on his 3rd birthday. His mercury level was over 400% that of safe levels. It is important to note that this level was only indicative of what we were able to “elicit or sequester” out of him. His actual levels were far greater.

I started his treatments on his 3rd birthday, using a rudimentary version of the current TD-DMPS (DMPS in a transdermal base) that my partner, Dr. Dean Viktora and I had played around with a few years previously. By the age of 41 months, 5 months after initiating treatment with the TD-DMPS, my son started to speak, with such rapid progression of his speech that his speech therapist was noted to comment how she had never seen such rapid progress in speech in a child before. Today at the age of 5, Abie is far ahead of his peers, learning prayers in a second language, doing large mathematical calculations in his head, playing chess and already reading simple 3 and 4 letter words. His attention span and focus was sufficiently advanced to the point of being accepted as the youngest child into martial arts academy when he was only 4. His vocabulary is as extensive as any 10 year old’s, and his sense of humour, power to reason and ability to understand detailed and complex concepts constantly amazes me. This was the preliminary basis for our study that we initiated, which came about as a result of the extraordinary results obtained in the treatment of my son, Abie.

The Autism study consisted of 31 patients with the diagnoses of autism, autism like spectrum, and pervasive developmental delay. Inclusion criteria was simple, including an independent diagnosis of the above mentioned conditions from either a neurologist or paediatrician, and the desire of the parent to try the treatment protocol using TD-DMPS. All patients were enrolled sequentially as they presented to the clinic and only those who did not wish to participate in the TD-DMPS were not included.

All 31 patients were tested for metal toxicity using four different tests: urine metal toxicity and essential minerals, hair metal toxicity and essential minerals, RBC metal toxicity, and fecal metal toxicity, all obtained from Doctor’s Data Laboratory. These tests were performed at baseline, and repeated at 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, and then every 4 months there after. All 31 patients showed little or no level of mercury on the initial baseline test results. Slide #37 shows an example of a baseline test result of one participant in the study showing very little mercury. In addition, all study patients had chemistries, CBC with differentials, lipid panels, iron, thyroid profiles and TSH drawn every 60 days. Further specialized testing also included organic acid testing (OAT test) from Great Plains Laboratory and complete diagnostic stool analysis (CDSA) from Doctor’s Data Laboratory. If indicated, IgG mediated food allergy testing was also obtained but was not routinely performed.

Compared to the baseline results all 31 patients showed significantly higher levels of mercury as treatment continued. Slide #39 shows significantly higher mercury levels in this same study patient after two months of treatment with the TD-DMPS, with results showing approximately a 350% increase from previous baseline levels. The improvements in the patients in the study correlated with increased yield in measured mercury levels upon subsequent testing. Essentially, what was noted was that as more mercury was eliminated, the more noticeable the clinical improvements and the more dramatic the change in the patient.

The manifestations of this evidence for clinical improvements included many observations but were specifically quantifiable with some patients who had no prior history of speech starting to speak at the age of 6 or 7, sometimes in full sentences. Patients also exhibited substantially improved behavior, reduction and eventual cessation of all stemming behaviour, return of full eye contact, and rapid potty training, sometimes in children that were 5 or 6 but had never been successfully potty trained. Additional findings reported by parents included improvement and increase in rate of physical growth increased, as well as the child beginning to follow instructions, becoming affectionate and social with siblings or other children, seeking interaction with others, appropriate in response, and a rapid acceleration of verbal skills. The results in many of these children has been documented on video and other physicians involved with this protocol have been successfully able to reproduce the same results.

DMPS, or dimercaptopropane – 1 sulfonate, is a primary chelator for mercury and arsenic.
Slide 42 shows the chemical structure of DMPS. DMPS has pitfalls as well as advantages.

The pitfalls include oral dosing which is the usual recommended dosing because it is approximately 50% to 55% absorbed by the gastrointestinal mucosa. As a result of already compromised gastrointestinal function and dysbiosis noted in most of these children, there is also be a decreased absorption of the DMPS when dosed orally, and with the severe gut vacillations prevalent in our society, DMPS by mouth becomes impractical. Most of the children that have taken the DMPS orally for more than 1 week continuously, begin complaining of abdominal pain, cramping and other GI distress. We tried the oral DMPS for almost 6 weeks before eliminating it as a possible therapeutic method. Intravenous methods of application were not an option in children so young, although is the preferred method I have used in my clinical practice for my adult patients with mercury toxicity.

All study patients were also monitored for renal function, and mineral depletion. The key to success with this study was the constant and continuous “pull” of mercury by being able to dose it every other day and the compliance of patient and parents. Each patient was put on a protocol consisting of the transdermal DMPS (TD-DMPS). Transdermal DMPS is DMPS conjugated with a number of amino acids, delivered in highly specialized micro-encapsulated liposomal phospholipid transdermal base with essential fatty acids. The frequent dosing is one of the most important components of the TD-DMPS. It is important to note that DMPS is highly oxygen reactive and is very unstable when exposed to air.

This and many other issues of delivery, stabilization, and oxidation have all been successfully identified and resolved over the last two years with the final result now pending patent. In addition, certain other components have been added to the TD-DMPS to potentiate the efficacy of treatment, such as the addition of various amino acids and glutathione. There are a number of agents that have been demonstrated to have clinical utility in facilitating the removal of mercury from someone who has demonstrated clinical signs and symptoms of mercury toxicity. The most important part of this systemic elimination process, however, is the removal of the source of mercury. Once this has been completed, treatment for systemic mercury detoxification can begin. The following is a summary of the most effective agent as well as the most commonly used agent that have been documented in the peer-reviewed literature.

• DMPS
  • The chemical name is Sodium 2,3 dimercaptopropane-1-sulfonate, this water soluble dimercaprol has 2 active sulfhydryl sites that form complexes with heavy metals such as zinc, copper, arsenic, mercury, cadmium, lead sliver, and tin.
  • The chemical structure of DMPS is:
    CH2 – CH – CH2 – S – O3 – NA | |SH SH
  • DMPS was developed in the 1950’s by the Soviets as an antidote for the chemical warfare agent Lewisite.
  • It became commercially available in 1978, being produced by the German pharmaceutical company Heyl.
  • There has been extensive research in both safety and effectiveness of this drug in the 50 years of its existence and it is now considered to be the most effective therapy for the treatment of mercury toxicity, as mercury is bound to sulfur groups throughout the body and is therefore difficult to remove. The sulfur groups on this compound readily unseat the mercury from its attachment to sulfur in our tissues, then this compound is excreted through the kidneys unchanged.
  • DMPS is widely available throughout the United States as a compounded bulk drug and has been recognized by the FDA in that capacity.
  • DMPS is very safe when used properly. Side effects are very rare, but may include allergic reactions such as skin rashes. Most important is to monitor and supplement with appropriate doses of zinc and copper as these minerals are bound readily by DMPS in the same way as it binds mercury. This should be done prior to commencement of any DMPS treatment regimen, then periodically throughout the process.
  • DMPS can be taken orally, as over 50% is absorbed. Most trained chelation physicians in the United States utilize intravenous challenges, whereas most European physicians will challenge with oral DMPS.
  • Currently, the only professional medical organizations that teach and certify physicians in chelation therapy are the International College of Integrative Medicine and the American College for Advancement of Medicine. Both of these organizations periodically conduct workshops on mercury toxicity specifically with emphasis on both basic science knowledge and clinical evaluation and treatment.
  • With the increased concern of mercury toxicity as an environmental health threat and in recognition of the need to increase basic science research and clinical treatment of heavy metal toxicity, the American Board of Clinical Metal Toxicology was recently formed as an evolution of the American Board of Chelation Therapy. This Board will now expand greatly the educational opportunities for physicians interested in this health problem and offer certification procedures that will expand even further the work that has already been done.
  • As a result of the work of these organizations, a general protocol for the use of DMPS has been established which most certified physicians follow.
• DMSA
  • 2,3 dimercaptosuccinic acid is also a dithiol, like DMPS, and therefore is more effective that EDTA in removing mercury.
  • Structure: HOOC – C – C – COOH | | SH SH
  • This chelator is an oral agent that is reportedly effective in removing both lead and mercury and is used frequently to treat children.
  • DMSA removes mercury both by way of the kidneys, though urine, and the liver, through bile and then the intestines.
  • DMSA has several disadvantages but also some advantages relative to DMPS:
    • DMPS remains in the body for a longer time than DMSA, therefore it is able to more thoroughly bind to mercury and eliminate greater amounts per treatment.
    • DMPS acts more quickly than DMSA.
    • DMPS is given intravenously, intramuscularly, or orally while

    DMSA is strictly an oral preparation.

  • DMSA is now thought to be potentially harmful if used in patients with excessively high levels of mercury. Therefore, DMSA is recommended for use only late in the mercury elimination process after the peripheral tissue load of mercury has been reduced by DMPS.

  In our observation, DMSA did not show efficacy in removing mercury. Slides #26 and #29 show a comparison in the effect of pulling out mercury, completed less than 30 days apart in my son’s case. The yield of DMPS compared to DMSA for removal of mercury in this example was 10 to 1. There is an intriguing explanation provided by Boyd Haley, DSc, to support my clinical observations to the lack of efficacy observed with the use of DMSA in treating children with autism and developmental delays. DMSA stands for dimercapto-succinic acid. Succinic acid is a major substrate in the citric acid cycle and DMSA is an analog of succinic acid.

  Therefore, DMSA would most likely act as an inhibitor of the enzyme in the citric acid cycle that uses succinic acid as a substrate. This would result in DMSA actually acting as a competitive inhibitor of succinic acid and in turn, would lead to a slowing down of, or inhibition of the citric acid cycle. Succinate produces FADH2 which is directly coupled to the electron transport chain and leads to ATP production. The competitive inhibition of this succinic acid by DMSA would thus, eventually result in an inhibition of ATP production leading to decreased energy utilization causing a significant burden and impaired ability of the physiological system to function correctly.

  In our clinical experience, the only effective method that has resulted in the consistent removal of mercury resulting in the elimination of this “spark” in the pediatric population is the TD-DMPS that was originally formulated only for the purposes of treating my son’s developmental delay. Since it’s implementation, we have now successfully treated scores of patients, many of whom have completely recovered but all of whom have improved since the implementation of this treatment. These results have been duplicated by other physicians involved with the care of patients with neurodegenerative disease processes.

  Children with Autism (mercury toxicity) have many resulting imbalances in their systems, including but not limited to significant allergies, systemic candidiasis, hormonal imbalances, gastrointestinal dysbiosis, immune dysfunctions, nutritional deficiencies, etc. However these are what I refer to as the “fires” of autism. All these, and other “fires” of autism result from one “spark”. Mercury! Successfully addressing many or all of these “fires” will accomplish transient improvement but until the “spark” that constantly re-ignites these “fires” has definitively been eliminated, any improvement will be short lived at best. Mercury is NOT the fire. It is however, the spark that ignites and constantly re-ignites these “fires”. In addition, this particular patient population seems to have antibodies to mercury binding fibrillarin, confirming the fact that mercury is the cause. But it’s the spark, not the fire. Until the spark is eradicated, the fire will continue to re-start and damage the brain and other vital areas such as the immune system. Mercury is the underlying common denominator of all the problems from which these children suffer.

  Children diagnosed with autism suffer from acute mercury toxicity secondary to huge exposure while in utero (maternal amalgam load, dietary factors, maternal inoculations, Rhogam injections, etc.) and early on in life (vaccinations preserved with thimerosal, etc.).

  Adults diagnosed with Alzheimer’s suffer from chronic, insidious mercury toxicity secondary to exposure over a long time (amalgam load, inhalation of mercury vapors, combustion of fossil fuels, dietary factors, etc.). By addressing and eliminating the mercury “spark”, these secondary “fires” become far easier to manage clinically and the improvements realized from treatment of the resulting imbalances become easier to maintain.

  Mercury directly causes damage to the neuronal cell resulting in denudation of the neurofibrils. In addition, mercury results in secondary problems as discussed such as immuno-suppression, allowing for opportunistic infections, allergies, GI dysbiosis, etc.

  Addressing all other issues such as immuno-suppression in children with Autism without addressing the issue of mercury, is analogous to attempting to put out multiple fires without addressing the arsonist. The fire will keep re-igniting unless the “spark” is eliminated. It is the elimination of this “spark”, i.e. mercury, for which we now have an easy and effective solution. Along with some supportive therapies, autism and certain other neurodegenerative diseases can be fully and permanently reversed. This is NOT a theory but rather, a protocol that has already been clinically validated and the evidence is irrefutable.

  The reason for some individuals to have severe damage from mercury where others do not have serious adverse neurological deficits extends due to various factors which include biological individuality and genetic predisposition. In addition, what type of toxicity exposure the individual was exposed to, was it inhaled, ingested, or exposed on their skin?

  What type of mercury exposure did the individual receive? Was it organic or inorganic mercury? If it was organic, was it ethyl mercury or methyl mercury? How frequent was the exposure to the source of toxicity? Was there a significant maternal load present prior to birth? Was the situation exacerbated by the mother being inoculated, or having Rhogam administration. How many administrations took place and over what period of time? What about the diet? How about the proximity to industrial sites, and exposure to combustion of fossil fuel? As you can see, the variables are extensive. But the treatment is essentially the same. The only difference is the extent of continuity of treatment.

  Slide 47 shows a newspaper article in the Charlotte Observer with a picture showing one of my patient’s mother administering transdermal DMPS to her son’s forearms. Slide 48 gives more information on metal toxicity and represents the focus of the majority of my post graduate medical career revolving around the issue of the effective clinical treatment of heavy metal toxicity.

  

  Summary:

  The underlying common denominator in chronic neurodegenerative disease seems to be either decreasing vascular supply (less blood to the brain) or accumulation of heavy metals, specifically mercury. The inability of an individual to eliminate toxic metals, especially mercury, is directly related to the level of neurodegeneration experienced. In the young patient population suffering from Autism or Pervasive Developmental Delay, the vascular supply is not an issue. The underlying pathology of children with autism and the geriatric population with Alzheimer’s is of the same etiology, specifically mercury toxicity.

  Both these patient populations suffer from the inability to excrete mercury as a result of a genetic predisposition resulting from the Apo E allele. This allele appears to be associated with the inability to get rid of mercury from the system. If these patient populations inhabited a complete mercury free environment, they would not have the problems associated with autism or Alzheimer’s. When the mercury is successfully removed from their systems, these individuals begin to significantly improve due to a cessation of the destruction and denudation of the neurofibrils, as evidenced by steady improvement in cognitive function.

  Mercury is the “spark” that causes the “fires” of Autism as well as Alzheimer’s. Autism is the result of high mercury exposure early in life versus Alzheimer’s is a chronic accumulation of mercury over a life time. A doctor can treat ALL the “fires” but until the “spark” is removed, there is minimal hope of complete recovery with most improvements being transient at best. However, once the process of mercury removal has been effectively started, the damage is curtailed and full recovery becomes possible and enhanced by utilizing various additional therapies including nutrition, hyperbarics, etc.

Risperidone is a drug used in Psychiatric Medicine to treatment cases of Schizophrenia, a form of insanity. It acts on certain specific receptors on the brain that help to modify the behavior of persons so afflicted.

Autism is a developmental disability of unknown etiology, initiated by at least 6 to 7 major genes and about 3 to 4 times that number of minor genes, causing a wide variety of medical pathologies. One of those genes that may have something to do with the presence of the HOXA1 gene coupled with the presence of mercury in the body. the metal gets incorporated into the neural proteins to cause their dysfunction. This causes the characteristic abnormal dissociated behavior patterns seen in children with Autism Spectrum disorder.

Now comes an unusual trial report that Risperidone may have at least short-term benefits in Autism, when used at a low dosage.

The Report

Risperidone is well-tolerated and effective at treating behavioural symptoms associated with pervasive developmental disorders (PDD) and autism, according to the results of a randomised trial published in the November issue of Pediatrics.

“As yet, there are no pharmacological interventions that specifically target the core deficits of the PDD profile,” write Sarah Shea, MD, from IWK Health Centre and Dalhousie University in Halifax, Nova Scotia, Canada, and colleagues. “Risperidone is an antagonist of both dopamine (D2) and serotonin (5HT2A and others) receptors. Particularly when used at lower doses, risperidone proved to be relatively free of the extrapyramidal symptoms (EPSs) that had limited the use of conventional agents.”

In this eight-week, double-blind trial, 79 children, aged five to 12 years with PDD, were randomized to receive risperidone (0.01 to 0.06 mg/kg/day) or placebo solution. Mean risperidone dosage was 0.04 mg/kg/day (1.17 mg/day). Outcomes included behavioral scores on the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form (N-CBRF), and Clinical Global Impression-Change (CGI-C), as well as safety assessments including vital signs, electrocardiogram, EPSs, adverse events, and laboratory tests.

Compared with the placebo group, children in the risperidone group had a significantly greater mean decrease on the irritability subscale of the ABC, which was the primary endpoint. By study termination, improvement over baseline in the irritability score was nearly twice as high in the risperidone group as in the placebo group (64% vs 31%).

The risperidone group also fared significantly better on the other four subscales of the ABC; on the conduct problem, insecure-anxious, hyperactive, and overly sensitive subscales of the N-CBRF (parent version); and on the Visual Analog Scale (VAS) of the most troublesome symptom. Global improvement occurred in 87% of subjects treated with risperidone and in 40% of the placebo group.

Somnolence was the most frequently reported adverse event, occurring in 72.5% of subjects treated with risperidone and in 7.7% of the placebo group. However, this adverse effect responded to dose-dose-schedule modification. Compared with the placebo group, subjects treated with risperidone had statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure, but EPS scores were comparable between groups.

The main limitation of this study is the relatively short duration of treatment.

“Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children,” the authors write. “Risperidone was significantly more effective than placebo at alleviating irritability, hyperactivity/noncompliance, inappropriate speech, lethargy/social withdrawal, stereotypic behavior, conduct problems, hyperactive, insecure/anxious, and overly sensitive behaviors and the symptom identified as most troublesome….The encouraging efficacy outcomes achieved with this agent offer new hope for the management of behavioral symptoms exhibited by children with PDD.”

Summary: Secretin is a controversial enzyme therapy of AUTISM with some anecdotal reports of unexpected success but no standard well-controlled clinical trial proof of efficacy as yet. We include some reports and opinions on this subject.

Description

Secretin is an enzyme, administered intravenously, that is claimed to confer some benefits in selected cases of autism.
Trial report

A study on Secretin was reported in The New England Journal of Medicine of December 1999, one of the most respected medical journals in the world.
The study compared the effect of administration of Secretin to that of placebo (false /inert drug in identical looking formulation, to avoid bias) in patients of autism.

The study did not find any benefit in using the drug in Autism since it worked no better than a placebo in its first two rigorous studies, The authors suggest that there seems to be a significant placebo effect, but no difference between Secretin and placebo.

The authors suggest that the agent, Secretin should not be recommended to treat autism until the results of other ongoing studies are known, even though some children who participated in the study, did benefit from all the intensive care given to all.

Trial Protocol

Intravenous doses of Secretin – a digestive enzyme that costs $180 per vial – are used since anecdotal reports claimed benefit from the drug. Such reports prompted these studies where the drug is given to some children and the benefits compared to another group of children who are given a similar inert substance. Both groups are evenly matched in all parameters and given the same intensive care. Both batches of drug are packed in similar way and code marked. The identity of the drug is kept a secret and put in a sealed envelope, to be opened after the trial is over. Thus, neither the doctor actually handling the child and administering the drug knows the identity of the drug, nor does the patient.

Two studies are now published: (a) New England Journal of Medicine, December 1999, and (b) Medscape Internet site in October 1999 (by Dr.Edwin Cook, Univ. of Chicago). Neither found any benefit from Secretin.

The only benefit, seen in both groups (active drug and placebo) was due to the attention from doctors, parents and others. The actual benefits thus seemed to come only from long, painstaking work with behaviour or speech problems.

The other side of the coin for Secretin

Secretin is advocated by its patent holders: Bernard Rimland, Head of the Autism Research Institute in San Diego, and Victoria Beck, who first called attention to the enzyme after her son’s improvement. She has a 43-year-old autistic son, who is claimed to have improved significantly with Secretin.

Summary: Autism remains one of the enigmas of diagnosis and management. Theories of causation, pathology and remedies are thicker than flies. But, still we keep searching for the answer. This one concerns use of a very potent antibiotics to alter gut bacterial populations to decrease productions of some alleged neurotoxins that cause or aggravate autistic behavior, though for a short time only.

VANCOMYCIN

Vancomycin is a distinct class of antibiotics unrelated to the family of penicillins, streptomycin, cephalosporins, quinolones, sulfonamides, erythromycin, etc. that we use routinely in medical practice. Its use in medicine is reserved for the treatment of multi-drug resistant Staphylococcal infections that are life threatening. It is a toxic drug and its usage is best left to medical specialists.

AUTISM

What is autism and what causes it? We wish we knew more.

There are many useful bacteria in our gut that, by competition for food, inhibit the growth of many harmful bacteria in our gut. The extensive use of broad spectrum antibiotics therapy kills these normal and useful bacteria, and allow overgrowth of harmful intestinal infection, a condition called Super-Infection. Some of these harmful bacteria, so goes the theory, can produce nerve-killing toxins that enter the brain of a susceptible autistic child, to trigger, cause or aggravate autistic behavior. Oral Vancomycin could kill that infection, without being absorbed into systemic circulation (hence unlikely to cause immediate harm to the child).

A lady in Illinois had an autistic child. The child screamed for hours. He even chewed drywall from the walls. Complicating matters were severe diarrhea and other gastrointestinal problems. He had recurrent ear infections, for which antibiotics were prescribed shortly before he became autistic at 19 months. Based on her extensive studies in medical libraries, the mother theorized those drugs killed Andrew’s normal gut-protective bacteria and allowed an intestinal infection that can produce nerve-killing toxins to enter his brain. Vancomycin, she thought, could kill that infection.

Based on that hope, she managed to persuade a scientist to try oral vancomycin in her child to see if it might help her son’s severe autism. To their surprise, the child got better. He was not cured, but all of a sudden he started saying words and became toilet-trained. The scientists were intrigued as that was not expected to happen.

So the treatment was extended to eleven more autistic children who, like about a third of children with this serious brain disorder, also suffer painful gastrointestinal problems. Neuropsychological testing concluded that 10 children improved, though only for a while.
All the children worsened after just a few months. However, a little bit of the improvement remained, making it a little easier to manage them, though the remnant improvement was variable.

Dr. Michael Chez of Chicago plans to compare vancomycin to a dummy drug in a “Placebo controlled study” to find out if the improvements are genuine or merely the result of increased attention and care given to the children during the trial.

Scientists are trying to study whether there is a cause and effect association between gut bacterial problems and brain function. At present, intense behavior therapy is autism’s only proven treatment. The famous secretin therapy of autism already seems to be falling by the wayside. Some other nutritional aids and vitamins provide some help though they are not curative. Will vancomycin or an allied antibiotics hold a future therapeutic key ? Only more research will answer the question.

About vancomycin

Vancomycin is a macrolide glycopeptide class of antibiotics. It interacts with many drugs and may cause kidney, hearing, or balance dysfunction. Its adverse effects also include the following: skin rash, red neck, flushing, drug fever, low white blood cell count, increased eosinophil count in blood, allergic shock, low blood pressure, wheezing, and skin eruptions. Most of these reactions are seen only during injectable treatment.

Vancomycin is one of our main-stays against multi-drug resistant life threatening infection with Staphylococcus aureas or antibiotics induced large gut infection. If it is misused by indiscriminate oral therapy as above, then the bacteria may become resistant to vancomycin also, and we will have lost another important battle against drug resistant bacteria.

The July 1998 issue of Annals of Neurology, Joel Trugman et al described the use of a drug, commonly used in Parkinsonism, called Levo Dopa, in a 3 year old girl with symptoms similar to that of CP.

This girl could neither speak nor sit up or roll over on her own. The authors were able to treat the girl with an existing medicine, Levodopa (or L-dopa), that gave her the use of her muscles.

The mother had a clinical picture that was consistent with a disease called dopa-responsive dystonia. The mother’s symptoms included dystonia (slow muscle spasms that can involuntarily contort the body) and muscle cramps. It was discovered that the girl’s grandmother and great-grandmother also had similar symptoms. It was suspected that the child’s relatives suffered from an inherited form of dystonia that responds to L-dopa therapy: hereditary progressive dystonia/dopa-responsive dystonia (HPD/DRD).

However, that girl had been given one dose of L-dopa at the age of 18 months and had suffered a strong adverse reaction to the drug, and she flopped like a fish for four days. However, the authors decided that was a sign that she was perhaps responding to the medicine.

Despite misgivings, the mother allowed Trugman to give her daughter tiny doses of L-dopa in the hospital.

The girl tolerated the medication and the doses were gradually increased. During the following months, she began to develop simple speech and the ability to sit up and reach for things with her arms.

One of Trugman’s collaborators brought a similar patient to his attention: a 17-year-old boy who had walked a bit as a small child and learned to talk almost normally, but lost these abilities by the age of six. He also had reacted adversely to L-dopa. In his family tree there were no clinical signs of dystonia, though a great-grandfather had been diagnosed with Parkinson’s disease. Like the three-year-old girl, the boy improved dramatically — regaining speech and the use of his arms and hands — with low doses of L-dopa. Still, Trugman was unwilling to assign a diagnosis of HPD/DRD to these cases. Though they were responding to the L-dopa, both patients’ symptoms had been much more severe than those usually seen in HPD/DRD. They had also included unusual symptoms like eye-rolling and they had begun at a much earlier age.

Later the same year, 1994, other researchers provided another clue, finding that mutations in the gene that produces an enzyme called GTP-cyclohydrolase I (GCH) causes HPD/DRD. Significantly, mutations in the GCH gene are also the culprit in a hereditary form of a disorder called hyperphenylalaninemia. In hyperphenylalaninemia, excessive amounts of the chemical phenylalanine in fetuses and newborns are tied to neurological problems such as severe mental retardation and movement disorders, with symptoms that include eye-rolling.

Trugman and his colleagues noted that the young girl had mild symptoms of hyperphenylalaninemia, but didn’t have elevated levels of phenylalanine. Using more sophisticated biochemical tests, however, they found subtle problems with phenylalanine. When the girl later developed overt hyperphenylalaninemia, they were able to treat the condition and even accelerate her progress, with an experimental drug called tetrahydrobiopterin

.

Trugman’s collaborators at the Clarke Institute of Psychiatry in Toronto, Yoshiaki Furukawa, M.D., and Stephen Kish, Ph.D., then examined the DNA from these two families in search of mutations in the GCH gene. In the case of the girl, they found that the relatives with the mild form of HPD/DRD all had the same mutation in the GCH gene.

The key to the girl’s disease came from the father’s DNA. The researchers found that he also had a mutation of the GCH gene, though a different change to the gene and not one that had caused him any obvious neurological damage.

The girl then possessed two different defective GCH genes, one from each parent. The combined effect of the two mutant genes was to produce a disease that neither mutation could produce on its own. The boy’s genetic profile was similar; he also had received two different mutant GCH genes from his parents.

Thus, a new hereditary disease had been identified, with biochemical and clinical signs intermediate between the more severe hyperphenylalaninemia and the milder HPD/DRD, but related to the same gene as these diseases. And it can be treated with existing drugs.

The more personal ending to this medical detective story is that the girl, now seven years old, is walking and talking. She wears leg braces but has normal mental function and is doing better than ever expected in school. The boy walks with braces and functions well in a regular school classroom.

Summary: Children with brain damage severe enough to cause cerebral palsy, mental retardation, hydrocephalus, microcephaly, etc., may have concomitant epileptic fits originating from the damaged areas of brain. Such children may be given carbamazepine for control of their fits. This section discusses a few guidelines for the parent/caregiver of the disabled child. This section is a simplified account of that given in USP DI, and is included here only as a guide and with no commercial interest.

Brands available in India include Tegretol and Majetol, in strengths of 100, 200 and 400 mg tablets as well as oral suspensions for smaller children.

What is it ?

Carbamazepine is an anti-epileptic drug, used for various purposes by the doctor, which includes control some types of seizures and relieving pain due to some types of nerve diseases. In a CP/MR child, the only uses likely will be control of seizures.

Is it safe for your child ?

No drug on earth is absolutely safe. Not every doctor writes this drug. The few that do, usually know about its uses and risks. It is given only when the benefits of the drug outweigh the potential risks of NOT giving the drug.

How to make it easier for the doctor to decide about its use ?

• Be sure to inform the doctor about any history of allergy or drug intolerance, especially to carbamazepine use in the past, antidepressants of tricyclic family, or to any other substances, such as food items, cosmetics or other chemicals and household goods.
• Pregnancy: Most drugs are absolutely contraindicated in the first three months of pregnancy, and relatively contraindicated in the next six months, because we do not know for sure whether it is safe, nor can we do clinical trials in pregnancy since it is ethically not permitted. Hence we rely on animal usage data. As per animal data, carbamazepin can cause a wide variety of birth defects in off springs when given to the pregnant animals. Hence, be sure to tell the doctor if there is pregnancy or a chance of pregnancy in near future.
• Lactation: Carbamazepine is excreted in breast milk, and may therefore drug the baby. This is undesirable, hence the drug is best avoided during lactation. If that is not possible, then lactation should be avoided.

Unwanted effects

• Children: The drug is a brain acting drug, and may cause behavioral changes in children
• Adults: Even adults may suffer from confusion, restlessness, nervousness; palpitation or irregular or slow heart beats, chest discomfort, etc.

Drug to drug interaction

Anticoagulants to thin the blood: their effects may be decreased. Regular monitoring of the blood thinning effects is needed.

Clarithromycin, a popular antibiotic for respiratory and other infections: increases the blood levels of carbamazepine to cause adverse effects described earlier.

Corticosteroids, may be used for severe inflammations, asthma, severe allergies, etc. Carbamazepine decreases the effects of corticosteroids.

Diltiazem, Verapamil, Erythromycin or Propoxyphene : These drugs increase the blood levels of carbamazepine to increase sedation and other such adverse effects.

Estrogens (female hormones) or Birth Control pills containing estrogen or Quinidine : Carbamazepine decreases the effects of these drugs and may lead to hormonal disturbances, failure of birth control, or loss of control of heart rhythm, respectively.

Isoniazid is a common anti-TB drug., whose liver side effects may be increased.

Itraconazole or Ketoconazole are systemic anti-fungal drugs, whose effects may be decreased.

Monoamine oxidase inhibitors, furazolidone, selegiline, etc.: Use of carbamazepine within 2 weeks after these drugs may cause sudden high temperature, high BP, fits, etc.

Other drug interactions involve

• Other Anti-epileptic drugs
• Risperidone
• Alcohol abuse
• Anemia or other blood problems
• Behavioral problems
• Glaucoma
• Heart or blood vessel disease
• Urinary obstructive disorders
• Diabetes mellitus
• Kidney or Liver disease

How to use this drug

• Take after food to avoid stomach upsets
• Long acting preparations do not have the above limitations. However, these preparations should not be broken into two parts unless there is a dividing line provided by the manufacturers.
• Carbamazepine is not an ordinary pain reliever, but a critical brain-acting drug. it must be taken at the exact dose prescribed, and exactly at the times advised, for the exact duration advised. Never suddenly stop taking this medicine without first checking with the doctor .
• Store this medicine in a cool dark dry place, away from the reach of children. Store away from heat and direct light. Do not freeze the liquid form of this medicine. Discard outdated medicine or medicine no longer needed.
• Make regular follow up visits to the doctor at prescribed intervals, as he may want to adjust the dose or do some blood tests and check-ups to ensure that there are no adverse effects.
• Stay out of direct sunlight, and wear protective clothing, hat, sunglasses, sunscreens, etc.

When to make emergency calls to doctor

When any of the following occur: Black, tarry stools; blood in urine or stools; bone or joint pain; cough or hoarseness; darkening of urine; lower back or side pain; nosebleeds or other unusual bleeding or bruising; painful or difficult urination; pain, tenderness, swelling, or bluish color in leg or foot; pale stools; pinpoint red spots on skin; shortness of breath or cough; sores, ulcers, or white spots on lips or in the mouth; sore throat, chills, and fever; swollen or painful glands; unusual tiredness or weakness; wheezing, tightness in chest, or troubled breathing; yellow eyes or skin.

How to know that there is an overdose

Brain related: Body spasm in which head and heels are bent backward and body is bowed forward; clumsiness or unsteadiness; convulsions (seizures)—especially in small children; dizziness (severe) or fainting; drowsiness (severe); large pupils; nausea or vomiting (severe); overactive reflexes followed by under active reflexes; poor control in body movements (for example, when reaching or stepping)

Heart / B.P. related: fast or irregular heartbeat; high or low blood pressure (hypertension or hypotension); irregular, slow, or shallow breathing

Body function related: sudden decrease in amount of urine; trembling, twitching, or abnormal body movements

Miscellaneous:

• More common: Blurred vision or double vision; continuous back-and-forth eye movements
• Less common: Behavioral changes (especially in children); confusion, agitation, or hostility (especially in the elderly); diarrhea (severe); headache (continuing); increase in seizures; nausea and vomiting (severe); skin rash, hives, or itching; unusual drowsiness
• Rare: Chest pain; difficulty in speaking or slurred speech; fainting; frequent urination; irregular, pounding, or unusually slow heartbeat; mental depression with restlessness and nervousness or other mood or mental changes; muscle or stomach cramps; numbness, tingling, pain, or weakness in hands and feet; rapid weight gain; rigidity; ringing, buzzing, or other unexplained sounds in the ears; sudden decrease in amount of urine; swelling of face, hands, feet, or lower legs; trembling; uncontrolled body movements; visual hallucinations (seeing things that are not there)

Other side effects that are often self limiting and do not usually require medical remedial action include:

• Common: clumsiness or unsteadiness; dizziness (mild); drowsiness (mild); light-headedness; nausea or vomiting (mild)
• Less common or rare: aching joints or muscles; constipation; diarrhea; dryness of mouth; headache; increased sensitivity of skin to sunlight (skin rash, itching, redness or other discoloration of skin, or severe sunburn); increased sweating; irritation or soreness of tongue or mouth; loss of appetite; loss of hair; sexual problems in males; stomach pain or discomfort.
• This is not a full list of side effects. If any side effect not listed above is noted, inform the doctor.

Summary: Brain damage that can cause cerebral palsy may also cause epileptic fits. Such children need an effective anti-epileptic like valproic acid to control the fits along with management of CP This section is a simplified account of that given in USP DI, and is included here only as a guide and with no commercial interest.

Description

Valproic acid and valproate sodium belong to the group of medicines called anticonvulsants. They are used to control certain types of seizures in the treatment of epilepsy. Valproic acid and valproate sodium may be used alone or with other seizure medicine. These medicines are available only with your doctor’s prescription, in the following dosage forms:

Valproic Acid

• Tablets
• Syrup

Before Using This Medicine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This decision is made by the doctor depending upon his judgment and the information you give him :

Allergies

History if any of allergic reaction to valproic acid or valproate sodium, or to any other substances, such as foods, preservatives, or dyes.

Pregnancy

Valproic acid and valproate sodium have been reported to cause birth defects when taken by the mother during the first 3 months of pregnancy. However, these medicines may be necessary to control seizures in some pregnant patients. Be sure to discuss this possibility with your doctor

.

Lactation

Valproic acid and valproate sodium pass into the breast milk, but their effect on the nursing baby is not known. Be sure to discuss this with your doctor.

Children

Abdominal or stomach cramps, nausea or vomiting, tiredness or weakness, and yellow eyes or skin may be especially likely to occur in children, who are usually more sensitive to the effects of these medicines. Children up to 2 years of age, those taking more than one medicine for seizure control, and children with certain other medical problems may be more likely to develop serious side effects.

Senior Citizens

The elderly people are especially sensitive to the effects of these medicines. This may increase the chance of side effects during treatment, hence they need a lower dose

Drug Interactions

It is important that your doctor should be aware if you are taking any of the following commonly used drugs (the actual list is very vast):

• Acetaminophen / Paracetamol (Crocin, etc)
• Amiodarone (Cordarone, etc.)
• Anabolic steroids (Durabolin, etc.)
• Androgens (Testosterone, etc.)
• Barbiturates(Luminal, etc.)
• Carbamazepine (Tegretol, etc.)
• Estrogens (female hormones)
• Methyldopa (Alfadopa, etc.)
• Phenothiazines (promethazine – Phenergan, etc)
• Central nervous system (CNS) depressants (Calmpose, etc.
• Tricyclic antidepressants (Tryptomer, etc.)
• Inflammation or pain medicine, except narcotics (Brufen, etc.)
• Pentoxifylline (Trental, etc.)
• Heparin (increased risk of bleeding)
• Mefloquine (Mefloq, etc.)
• Any other anticonvulsant

Other medical problems

• Blood disease
• Brain disease
• Kidney disease
• Liver disease

Dosage

• Adults and adolescents:

  5 to 15 milligrams (mg) per kilogram (kg) body weight up to a maximum of 60 mg/kg/day.

  Doses above 250 mg/day are given in divided doses.

• Children 1 to 12 years of age:

  15 to 45 mg per kg body weight, up to a maximum of 100 mg/kg/day.

Missed dose

If you miss a dose of this medicine, and your dosing schedule is:

• One dose a day: Take the missed dose as soon as possible. However, if you do not remember until the next day, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
• Two or more doses a day: If you remember within 6 hours of the missed dose, take it right away. Then take the rest of the doses for that day at equally spaced times. Do not double doses.

If you have any questions about this, check with your doctor.

Storage:

To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store the capsule or tablet form of this medicine in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
• Keep the syrup form of this medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

Your doctor should check your progress at regular visits , especially for the first few months that you take this medicine. This is necessary to allow dose adjustments and to reduce any unwanted effects.

Do not stop taking this medicine without first checking with your doctor . Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

Before you have any medical tests, tell the doctor in charge that you are taking this medicine. The results of the metyrapone and thyroid function tests may be affected by this medicine.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine . Valproic acid, valproate sodium, or divalproex may change the time it takes your blood to clot, which may increase the chance of bleeding. Also, taking valproic acid, valproate sodium, or divalproex together with medicines that are used during surgery or dental or emergency treatments may increase the CNS depressant effects.

Valproic acid, valproate sodium, and divalproex will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine .

For diabetic patients:

• This medicine may interfere with urine tests for ketones and give false-positive results.
• Your doctor may want you to carry a medical identification card or bracelet stating that you are taking this medicine.
• This medicine may cause some people to become drowsy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are drowsy or not alert .

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

Less common

Abdominal or stomach cramps (severe); behavioral, mood, or mental changes; continuous, uncontrolled back-and-forth and/or rolling eye movements; double vision; increase in seizures; loss of appetite; nausea or vomiting (continuing); spots before eyes; swelling of face; tiredness and weakness; unusual bleeding or bruising; yellow eyes or skin

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

More common

Abdominal or stomach cramps (mild); change in menstrual periods; diarrhea; hair loss; indigestion; loss of appetite; nausea and vomiting; trembling of hands and arms; unusual weight loss or gain

Less common or rare

Clumsiness or unsteadiness; constipation; dizziness; drowsiness; headache; skin rash; unusual excitement, restlessness, or irritability

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

Summary: Baclofen is a powerful injectible and oral drug that may occasionally be prescribed by a doctor for the relief of muscle spasticity, that includes many causes, one of which may be cerebral palsy. The text of this paper is adapted from the information given by USP DI

Description

Baclofen is used to help relax certain muscles in your body. It relieves the spasms, cramping,and tightness of muscles caused by medical problems such as multiple sclerosis or certain injuries to the spine. Baclofen does not cure these problems, but it may allow other treatment, such as physical therapy, to be more helpful in improving your condition.

Baclofen acts on the central nervous system (CNS) to produce its muscle relaxant effects. Its actions on the CNS may also cause some of the medicine’s side effects. Baclofen may also be used to relieve other conditions as determined by your doctor.

This medicine is available only with your doctor’s prescription, in the following dosage form:

• Oral
• Tablets

Before Using This Medicine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For baclofen, the following should be considered:

Allergies: Tell your doctor if you have ever had any unusual or allergic reaction to baclofen. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes

.

Pregnancy: Studies on birth defects with baclofen have not been done in humans. However, studies in animals have shown that baclofen, when given in doses several times the human dose, increases the chance of hernias and incomplete or slow development of bones in the fetus, and of lower birth weight.

Breast-feeding: Baclofen passes into the breast milk. However, this medicine has not been reported to cause problems in nursing babies.

Children: Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of baclofen in children with use in other age groups.

Older adults: Side effects such as hallucinations, confusion or mental depression, other mood or mental changes, and severe drowsiness may be especially likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of baclofen.

Other medicines: Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary.

When you are taking baclofen, it is especially important that your health care professional know if you are taking any of the following:

• Antidepressants, especially tricyclics family
• Central nervous system (CNS) depressants (medicines that causes drowsiness) since there may be an increased incidence of drowsiness

Other medical problems: The presence of other medical problems may affect the use of baclofen. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes mellitus : Baclofen may raise blood sugar levels
• Epilepsy or
• Kidney disease or
• Mental or emotional problems or
• Stroke or other brain disease: The chance of side effects may be increased

Proper Use of This Medicine

Dosing: The dose of baclofen will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of baclofen. If your dose is different, do not change it unless your doctor tells you to do so.

• • For oral dosage form (tablets):
  • For muscle relaxation:
    • Adults and teenagers: At first, the dose is 5 milligrams (mg) three times a day. Then, each dose may be increased by 5 mg every three days until the desired response is reached. No more than 80 mg should be taken within a twenty-four-hour period.
    • Children: Use and dose must be determined by your doctor.

Missed dose: If you miss a dose of this medicine, and you remember within an hour or so of the missed dose, take it as soon as you remember. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage: To store this medicine:

• • • Keep out of the reach of children.
    • Store away from heat and direct light.
    • Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
    • Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

Precautions

Do not suddenly stop taking this medicine.Unwanted effects may occur if the medicine is stopped suddenly. Check with your doctor for the best way to reduce gradually the amount you are taking before stopping completely.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; other muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using baclofen.

This medicine may cause drowsiness, dizziness, vision problems, or clumsiness or unsteadiness in some people. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert, well-coordinated, and able to see well.

For diabetic patients :

• • • This medicine may cause your blood sugar levels to rise. If you notice a change in the results of your blood or urine sugar test or if you have any questions about this, check with your doctor.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• • • Less common or rare
      • Bloody or dark urine; chest pain; fainting; hallucinations (seeing or hearing things that are not there); mental depression or other mood changes; ringing or buzzing in the ears; skin rash or itching
    • Symptoms of overdose
      • Blurred or double vision; convulsions (seizures); muscle weakness (severe); shortness of breath or unusually slow or troubled breathing; vomiting

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

• • • More common
      • Confusion; dizziness or lightheadedness; drowsiness; nausea; unusual weakness, especially muscle weakness
    • Less common or rare
      • Abdominal or stomach pain or discomfort; clumsiness, unsteadiness, trembling, or other problems with muscle control; constipation; diarrhea; difficult or painful urination or decrease in amount of urine; false sense of well-being; frequent urge to urinate or uncontrolled urination; headache; loss of appetite; low blood pressure; muscle or joint pain; numbness or tingling in hands or feet; pounding heartbeat; sexual problems in males; slurred speech or other speech problems; stuffy nose; swelling of ankles; trouble in sleeping; unexplained muscle stiffness; unusual excitement; unusual tiredness; weight gain

Some side effects may occur after you have stopped taking this medicine, especially if you stop taking it suddenly. Check with your doctor immediately if any of the following effects occur:

Convulsions (seizures); hallucinations (seeing or hearing things that are not there); increase in muscle spasm, cramping, or tightness; mood or mental changes; unusual nervousness or restlessness

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

Summary: Tizanidine is a muscle relaxant drug that is being used to provide useful anti-spasmodic activity in muscles to help persons with Cerebral Palsy achieve a more useful activity from their limbs. This section is a simplified account of that given in USP DI, and is included here only as a guide and with no commercial interest.

Principal Uses

Tizanidine (avaiable as SIRDALUD and a number of combinations with pain-killers) is a drug that relaxes the voluntary muscles of the body. It is used to relieve the muscle spasticity and cramping associated with multiple sclerosis, spinal cord injury, bone and joint diseases causing reflex muscle spasm, and now, muscle spasm in cerebral palsy.

Mode of action

Tizanidine is a short-acting drug that temporarily inhibits nerve activity that causes spasticity. Because of the risk of side effects, it should be taken only at times of the day when reduced spasticity is most important.

Dosage guidance

<p>Initial dose: 4 mg, every 6 to 8 hours. This may be increased as needed in 2 to 4 mg increments to 8 mg every 6 to 8 hours (not exceeding 3 doses in 24 hours), until a satisfactory therapeutic effect is achieved. Maximum dose is 36 mg a day.

Onset of Effect: Within 1 hour.

Duration of Action: Up to 6 hours.

Dietary Advice: It can be taken with or between meals. Dry mouth is a common complaint with such drugs; maintain adequate fluid intake and suck on ice chips if desired.

Missed dose : Take it as soon as you remember. If it is near the time for the next dose, skip the missed dose and resume your regular dosage schedule. Do not double the next dose.

How long to take? : The decision to stop taking the drug should be made by your doctor. Those taking it for a long period should see the doctor regularly for tests and examinations as required.

How to store the drug

Store in a tightly sealed container away from heat and direct light. Precautions

• Adverse reactions may be more likely and more severe in older (aged above 60 years) patients.
  caution is needed for driving or doing hazardous work, as the drug may cause sedation leading to risk of accidents.
• Avoid alcohol when taking the drug due to risk of additive sedation

Pregnancy

In some animal studies, large doses of tizanidine have been shown to cause problems. Human studies have not been done. This drug should be used during pregnancy only if clearly needed. Consult your doctor for advice.

Breast Feeding

Tizanidine may pass into breast milk and sedate the child. Consult your doctor for advice before breast feeding.

Infants and Children

There is no specific information about the use of tizanidine in infants and children.

Special Concerns

Tizanidine is a newly introduced medication, and it is possible that side effects not found in early studies may occur with widespread use. Patients should be alert for the signs of significantly lowered blood pressure (dizziness, faintness, disorientation). In clinical trials of tizanidine, a small number of patients experienced hallucinations that continued after treatment was stopped. Dose-related eye damage (retinal degeneration and corneal opacities) was detected in some animal studies but has not been seen in human clinical trials.

Overdose Symptoms:

Loss of consciousness and respiratory depression have been noted thus far in limited experience with the drug. Other symptoms may occur.
Drug Interactions

Tizanidine may have a variety of drug interactions with many drugs, requiring adjustment of drug dosage to suit an individual patient as per clinical findings. These particularly relate to the following:

• High blood pressure medicine
• Birth control pills
• Phenytoin for epilepsy
• Kidney or Liver disease: Increased chances of side effects due to delay in getting rid of the drug from the body.

Side Effects

More common: Fever; loss of appetite; nausea and/or vomiting; nervousness; pain or burning while urinating; sores on the skin; tingling, burning, or prickling sensations; yellow eyes or skin

Less common: Black, tarry stools; bloody vomit; blurred vision; chills or sore throat; coldness; convulsions (seizures); cough; dry, puffy skin; eye pain; fainting; irregular heartbeat; kidney stones; seeing things that are not there; unusual tiredness or weakness; weight gain

Self limiting side effects not usually requiring medication: Anxiety; back pain; constipation; depression; diarrhea; difficulty in speaking; dizziness or lightheadedness, especially when getting up from a lying or sitting position; drowsiness; dry mouth; heartburn; increased sweating; increased muscle spasms or tone; muscle weakness; pain or burning in throat; runny nose; skin rash; sleepiness; stomach pain; uncontrolled movements of the body. Besides these, less common side effects may include difficulty swallowing; dry skin; joint or muscle pain or stiffness; loss of hair; migraine headache; mood changes; neck pain; swelling of feet or lower legs; swollen area that feels warm and tender; trembling or shaking; unusual feeling of well-being; weight loss

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