Chapter IV (Continued) - Medication and Diet Therapies
This section reviews the use of medication and diet therapies to treat manifestations of autism in young children. As research on autism has expanded in recent years, it has become the consensus of most researchers that that there is a biological basis for autism. This has coincided with a great expansion in knowledge over the past few decades about the chemical and physiological basis for a variety of neurological and psychiatric conditions and with the development of a large number of new medications to treat these conditions. All of these factors have contributed to an increased interest in the use of medications and diet as possible interventions for autism.
Types of medication and diet therapies
A number of medications and diet therapies have been suggested as possible treatments for autism. These proposed intervention methods are quite different in terms of the amount of scientific evidence supporting their use. For discussion in this section, these interventions are grouped in the following three major categories:
- Psychoactive medications
- Other medications
- Vitamin and diet therapies
The largest part of this section is devoted to reviewing the use of psychoactive medications for young children with autism. Psychoactive medications are those which primarily affect person's behavior, mood or thought processes. Many psychoactive medications that have been used to treat other neurological or psychiatric conditions have also been tried as treatments for autism.
In addition to psychoactive medications, other medications that have been proposed as treatments for autism include hormone medications (growth hormone and secretin), immunologic agents (immune globulin) and anti-yeast medications. The use of these other medications as treatments for autism is controversial and not generally accepted by the scientific community either because they have been shown to be ineffective or they have been insufficiently evaluated.
Therapeutic vitamins and special diets are also discussed in this section because they are sometimes suggested as possible treatments for autism. These interventions are also considered controversial.
|Some interventions evaluated
Some of the interventions for autism evaluated in this section are controversial and may not be generally accepted by the scientific community. However, information about the scientific evidence, or lack of evidence, about the efficacy and safety of these possible interventions for autism is included in this guideline because parents and professionals caring for young children with autism often have questions about them.
Quality and amount of research evidence
Over the past several decades, a large number of well-designed research studies have evaluated the efficacy of using various psychoactive medications for treating autism in both children and adults. Many of these studies were randomized controlled trials that used double-blind and placebo-controlled designs.
Some of the non-psychoactive medications and diet therapies reviewed in this section have been evaluated in a few adequately designed research studies in terms of their efficacy as treatments for autism. However, for many of the medications and diet therapies reviewed in this section, no adequately designed studies were found that evaluated the efficacy of these intervention methods for treating autism.
This section includes the following topics:
- General Approach for Using Medication or Diet Therapies as Interventions for Autism
- Psychoactive Medications
- Hormone Therapies
- Immunologic Therapies
- Anti-Yeast Therapies
- Vitamin Therapies
- Diet Therapies
Definition of psychoactive medication
Psychoactive medications are drugs that exert significant effects on mental functioning or behavior by altering the chemical makeup of the central nervous system. These medications have been developed primarily to treat a variety of neurological and psychiatric conditions.
Some types of psychoactive medications are intended to produce sedation, others to reduce agitation, and others to increase alertness or attentiveness. Still other types of psychoactive medications are intended to treat depression or disturbed thought processes. Most psychoactive medications can exert several of these effects to different degrees, and there is a certain amount of variation in their effects between individuals. As with all medications, psychoactive drugs have the potential for side effects and toxicity.
In addition to being used as possible treatments for autism, psychoactive medications are sometimes used to treat other conditions frequently seen in children with autism. While some of these uses are discussed briefly, an in-depth review of the use of psychoactive medications to treat conditions associated with autism was beyond the scope of the guideline.
Use of psychoactive medications to treat children with autism
At the current time, psychoactive medications are infrequently used in practice settings to treat autism in children under the age of 3 years. However, over the past few decades, several psychoactive medications have been evaluated in research settings to see if they are effective for treating some of the core manifestations of autism. Several psychoactive medications have been studied to determine if they can reduce maladaptive behaviors in young children with autism. A smaller number of psychoactive medications have been evaluated to see if they can increase social interaction in children with autism.
Psychoactive medication to treat maladaptive behaviors or social withdrawal
Several psychoactive medications have been proposed as possible treatments for reducing maladaptive behaviors in children with autism. Neuroleptics (often called major tranquilizers or antipsychotic drugs) and mood stabilizers (such as lithium) have been suggested as treatments to reduce agitation, tantrums, and aggression.
Stimulants (amphetamine-like drugs) and other medications used to treat children with attention deficit disorder (ADD) have been suggested as methods to treat hyperactivity and inattentiveness in children with autism. The opiate antagonist, naltrexone, has been proposed as a treatment to reduce self-injurious behavior. In addition, the selective serotonin re-uptake inhibitors (SSRI's), which are used to treat depression and obsessive-compulsive disorder, have been evaluated as possible methods to reduce maladaptive behaviors, especially perseverative behaviors.
There are fewer psychoactive medications that have been studied as methods to reduce social withdrawal and increase social interaction in children with autism. In the past, it had been hoped that the opiate antagonist naltrexone might reduce social withdrawal. Some newer atypical neuroleptics (like risperidone and olanzepine) may increase social interaction in some children with autism.
Psychoactive medications for conditions associated with autism
Psychoactive medications are sometimes also used to treat other associated conditions that are not part of autism but are frequently seen in children with autism. A variety of sedating medications are used to treat sleep disorders, which are often seen in children with autism. Associated mood disorders in children with autism are sometimes treated with antidepressants or mood stabilizers depending on whether one is treating depression or manic tendencies. Psychoactive medications are also sometimes used to treat anxiety disorders and tic disorders in children with autism.
Basis for These Recommendations
In evaluating the use of psychoactive medications in children with autism, the guideline panel reviewed only the evidence on the efficacy of these medications or treating the core manifestations of autism. Recommendations on the use of these medications to treat conditions co-existing with autism are based on panel opinion rather than a systematic review of the scientific literature. However, the panel felt that these recommendations were consistent with the current scientific research on these topics.General Approach for Using Medications or Diet Therapies as Interventions for Autism
|Evidence Ratings: [A] = Strong [B] = Moderate [C] = Limited [D1] = Opinion/No evidence meeting criteria [D2] = Literature not reviewed|
Evaluating potential benefits and risks of using medication or special diets
- It is recommended that careful consideration be given to the potential risks as well as the potential benefits of using medications or special diets to treat manifestations of autism in young children. [A]
- It is recommended that a decision to use a medication or special diet be guided by evidence of its effectiveness and safety in scientific studies using adequate research designs. [D2]
- In general, medication and diet interventions are not recommended as treatments for autism in young children until such intervention methods have been shown to be effective and safe for use in this age group. [D2]
- When discussing the use of medications or special diets for autism, it is important that professionals explain the potential harms and benefits to the child's parents. [D1]
Monitoring children taking medications or using special diets
- If professionals prescribe a medication or recommend a special diet to treat autism in a young child, it is important that they regularly monitor the child to:
- assess the effectiveness of the medication or special diet for improving targeted behaviors
- look for signs of adverse behavioral or health effects that may be related to use of the medication or special diet [A]
- If a child is receiving medication or a special diet for autism, it is important that parents and others caring for the child be able to recognize signs of potential side effects (including possible medication toxicity or nutritional deficiencies) and to know what to do if these occur. [A]
- After an adequate trial period of a medication or special diet, it is recommended that its continued use be periodically reevaluated. It is also recommended that a decision about whether or not to continue the medication or special diet be based on its demonstrated effectiveness in improving targeted behaviors in the child, balanced against concerns about side effects. [D1]
Evaluating potential benefits and risks of psychoactive medication to treat autism
- It is recommended that the use of psychoactive medication to treat maladaptive behaviors, social withdrawal, or other manifestations of autism in young children be considered only for children with severe or difficult behavior problems, and only if other interventions have not been effective. [A]
- It is recommended that careful consideration be given to the potential risks as well as the potential benefits of using psychoactive medication to treat manifestations of autism in young children. [A]
- It is important that physicians prescribing psychoactive medication for manifestations of autism in a young child discuss the potential risks and benefits with the child's parents. [D1]
Using a trial of psychoactive medication to treat autism in young children
- Psychoactive medication may be useful in some young children with autism who have severe behavioral problems that have not responded to behavioral techniques. Types of medications that can sometimes be useful include:
- mood stabilizers
- opiate antagonists
- selective serotonin re-uptake inhibitors (SSRIs)
- stimulants [A]
- In carrying out a trial of psychoactive medication to treat manifestations of autism, it is recommended that selection of a specific medication be guided by evidence of its effectiveness and safety in scientific studies using adequate research designs. [D2]
Using psychoactive medication to treat health problems associated with autism
- For some young children with autism who have severe sleep problems, a trial of sedating medications may be useful for inducing sleep. Such sedating medications include diphenhydramine, chloral hydrate, and the benzodiazepines. [D1]
- For children with autism who regress in their level of development, psychoactive medication may sometimes be useful for treating associated medical conditions suspected of precipitating the regression. [D2]
Monitoring children taking psychoactive medication for autism
- It is important that professionals prescribing psychoactive medication to treat manifestations of autism in young children regularly monitor the child in order to:
- assess the effectiveness of the medication for decreasing targeted behaviors
- look for signs of medication side effects or toxicity [A]
- If a child is receiving psychoactive medication for autism, it is important that parents and others caring for the child be able to recognize signs of potential medication side effects or toxicity and know what to do if these signs occur. [A]
- After an adequate trial period of the psychoactive medication, it is recommended that its use be reevaluated. It is also recommended that a decision about whether or not to continue the medication be based on its demonstrated effectiveness in decreasing the targeted behaviors in the child, balanced against concerns about side effects. [D1]
Experience and expertise of physicians
- It is recommended that physicians evaluating a young child with autism for possible use of psychoactive medication have:
- expertise treating young children with autism
- knowledge about the use of both medication and non-medication interventions for autism in young children
- knowledge of the potential benefits and risks of psychoactive medications that are considered
- experience in monitoring young children with autism on psychoactive medication, including:
- assessing the child's progress on the medication
- recognizing signs of side effects or toxicity
- making appropriate increases and decreases in dosage [D2]
- It is recommended that, when appropriate, early intervention programs facilitate consultation with a physician who has expertise in the use of psychoactive medication to treat autism in young children. [D2]
Hormones are complex chemicals naturally produced in the human body that aid in regulating many normal physiological functions, including digestion, metabolism, growth, temperature, and immune functions.
Several health problems in both children and adults are associated with deficiencies of particular hormones. Some hormone replacement therapies have been proposed as possible treatments for autism. In particular, adrenocorticotropin hormone (ACTH) and secretin (a hormone that helps regulate digestion) have been suggested as possible treatments for autism.
How hormones affect metabolism and growth
Hormones act primarily as chemical messengers that regulate metabolism, growth immune function and other physiological processes. A variety of hormones are produced by different endocrine glands in the body, including the adrenal, pancreas, pituitary, thymus, and thyroid glands. A number of hormone deficiency states that result in specific diseases have been identified in both children and adults.
In adults, the most common diseases involving hormone deficiencies are hypothyroidism and diabetes. In children, it is most common for hormone deficiency states to be associated with problems with retarded growth. Several medications have been developed to treat hormone deficiency states. Often these are slight chemical variations of the hormone, which are referred to as chemical analogs.
The role of ACTH
Adrenocorticotropin hormone (ACTH), one of several hormones produced in a part of the brain known as the pituitary gland, is also referred to as the growth hormone because it is involved in regulating growth and a variety of other processes in a normally growing child. When ACTH is circulating in the blood stream, it causes release of other chemical messengers from the adrenal glands and influences a variety of metabolic and immune processes in the body. A deficiency of ACTH in a child will result in stunted physical growth that can be treated with ACTH replacement therapy. ACTH has been suggested as a possible treatment for autism.
The role of secretin
Secretin is a polypeptide hormone secreted by the pancreas that plays a role in digestion. Secretin causes increased production of bicarbonate in the small intestine, helps to neutralize acid from the stomach, and aids in normal digestion.
A pharmaceutical preparation of secretin has been available for several years. The only approved medical use for secretin is as a diagnostic aid to evaluate normal functioning of the pancreas and digestive tract. This test is done by injecting a small amount of secretin into the blood and then measuring the level of bicarbonate in pancreatic secretions. At this time, secretin has not been approved as a treatment for any medical conditions.
Recently, secretin has been suggested as a possible treatment for autism in children. Interest in using secretin to treat autism developed after publication of case reports that purported to see an improvement in manifestations of autism in two children who had received secretin injections as part of diagnostic evaluations for gastrointestinal problems.
This treatment has received a great deal of recent media attention, but at this time no controlled studies have been done on the use of secretin for treatment of autism. The theoretical basis for a proposed link between secretin and a neurological disorder such as autism has not been clearly defined.
Evaluation of the use of hormone therapies in children with autism
There are multiple studies in the scientific literature on the use of hormone therapies to treat both hormone deficiency states and other types of diseases in children. This literature on the use of hormone therapy to treat conditions other than autism was not reviewed since this was considered beyond the scope of the guideline. However, a literature search was done on the use of hormones to treat autism in young children. Specific searches were also done on the use of ACTH and secretin, since these are the two types of hormone therapies that have been suggested as possible treatments for autism.
|Evidence Ratings: [A] = Strong [B] = Moderate [C] = Limited [D1] = Opinion/No evidence meeting criteria [D2] = Literature not reviewed|
- The use of hormone therapies (such as ACTH or secretin) is not recommended as a treatment for autism in young children, until such methods have been shown to be effective and safe for use in this age. [D1]
Immune or immunologic therapies, including treatment with intravenous immune globulin, have been suggested as a possible treatment for children with autism. Proponents of these therapies suggest that a subset of children with autism have abnormalities of their immune systems and state that for these individuals immunologic therapy may be useful as a treatment for autism. The use of immunological testing for children with autism is reviewed in Chapter III.
Immune globulin therapy
The only immunological therapy that is described in detail in the scientific literature as a treatment for autism is the use of intravenous immune globulin (IVIG). Pharmaceutical grade immune globulin is prepared commercially by separating immunoglobulin fractions from pooled human blood specimens. Several steps in the process are added to ensure that any live viruses or bacteria in the specimens are inactive so that these infections are not transmitted when IVIG is given.
Human immunoglobulin essentially consists of antibodies, which are complex chemical structures formed by a person's immune system that aid in fighting infections. The proponents of IVIG as a treatment for autism have not proposed a specific theory to explain why this treatment might be effective. Instead, IVIG has been proposed as both a replacement therapy for individuals with immune deficiency states and as a way to modulate the immune system (immunomodulary therapy) as a treatment for auto-immune and inflammatory diseases.
Special diets eliminating milk products and gluten have been suggested as a treatment for autism in children with food allergies. Even though allergies do involve the immune system, the use of special elimination diets is discussed in a separate part on Diet Therapies (at the end of this section) rather than in this part on Immunologic Therapies.
|Evidence Ratings: [A] = Strong [B] = Moderate [C] = Limited [D1] = Opinion/No evidence meeting criteria [D2] = Literature not reviewed|
- It is recommended that immune or immunologic therapies not be used for the treatment of autism in children. [D1]
- It is strongly recommended that intravenous immune globulin therapy not be used as a treatment for autism in children because of substantial risks and lack of proven benefit associated with this intervention. [D1]
- Immunological testing is not useful for guiding interventions for autism in children. Immunological tests provide no information that is either helpful in determining appropriate treatment for autism, or useful for predicting or measuring functional outcomes for children with autism. [D1]
Various anti-yeast therapies have been proposed as interventions for children with autism. These interventions typically involve administration of oral anti-fungal medication or special diets that include foods purported to have anti-fungal properties (such as garlic and grapefruit seed extract).
Where yeast is found on the body
Yeast, a type of fungus, is a common microorganism found widely in the environment. Candida is a common type of yeast that is normally found in humans on the skin, in the mouth, and in the intestinal tract (where it is considered part of the normal intestinal flora along with certain bacteria). In healthy individuals, there is a normal balance between the yeast and bacteria in the intestinal tract and mouth, so that the presence of these microorganisms does not result in any adverse health effects.
Common yeast and fungal infections and relationship to antibiotic use
When individuals take systemic antibiotics for bacterial infections, this can sometimes lead to an imbalance of the microorganisms in the intestinal tract or mouth, sometimes leading to an overgrowth of yeast. Such an overgrowth of yeast in children can have some temporary effects, such as loose stools, but the normal microbial balance in the gut usually returns on its own after a few days with no ongoing health effects. Yeast infections in other areas of mucous membranes, such as peri-anal or vaginal areas, can also sometimes occur after antibiotic use.
Occasionally, a child may develop thrush, a yeast infection of the mouth or throat that may require treatment with anti-fungal medications. In addition, young children can frequently develop fungal skin infections, especially under diapers or in moist skin folds, which may require topical fungal medication.
Except for these instances, health effects from yeast or fungal infections are uncommon for otherwise healthy children. Persons with significant immune suppression, such as persons with acquired immune deficiency syndrome or those receiving chemotherapy, can develop a number of more serious fungal and yeast infections, but such serious fungal infections are rare in persons with competent immune systems.
Proposed theoretical basis for using anti-yeast therapy
The use of anti-fungal therapies for autism is based on a theory that manifestations of autism in some children are either caused or aggravated by an overgrowth of yeast in the intestinal tract. The theory also suggests that yeast overgrowth in the intestines occurs after a child has been treated with antibiotics. The fact that some children who take antibiotics are affected and others are not is attributed by proponents to some unexplained underlying differences between children, perhaps relating to their immune system.
Proponents of this theory have suggested several possible mechanisms by which overgrowth of yeast in the intestinal tract may contribute to autism. One possible mechanism proposed by this theory is that the chemical metabolites produced by yeast in the intestinal tract are then absorbed into the blood stream and cause or aggravate a variety of medical conditions including autism. The purported mechanism of action is that that the yeast metabolites circulate throughout the body and interfere with normal metabolic processes, including the metabolism of glucose.
Description of proposed types of anti-yeast therapy
Some proponents of using anti-yeast therapy for autism suggest first testing urine for certain types of organic acids purported to be related to increased yeast growth. If an overgrowth of yeast in the intestinal tract is suspected, then proponents suggest treating this with oral anti-fungal medication. Proponents suggest that no specific optimal length of treatment has been established for persons taking oral anti-yeast medications for autism.
Proponents of anti-yeast therapies also suggest that eating certain foods (such as garlic and grapefruit seed) can inhibit the growth of yeast in the intestinal tract.
- Anti-yeast therapies, including the use of oral anti-fungal medications and special diets, are not recommended for the treatment of autism in children. [D1]
- Testing for specific organic acids (as a proposed marker for underlying yeast infection) provides no information that is either helpful in determining appropriate treatment for autism or useful for predicting or measuring functional outcomes for children with autism. [D1]
Oral administration of a high dose of Vitamin B6 (pyridoxine) combined with magnesium has been suggested as a possible treatment for children with autism. According to a recent review article on controversial therapies for autism (Nickel, 1996), vitamin B6 (pyridoxine) with magnesium was the vitamin therapy most frequently reported to be used as a treatment for autism in children.
In humans, pyridoxine is involved in the formation of several neurotransmitters, and deficiency of pyridoxine or magnesium can lead to significant neurological problems, including seizures and peripheral neuropathies. Documented vitamin B6 or magnesium deficiencies are typically treated by administering therapeutic doses of vitamin B6 or magnesium. Pyridoxine also has been proposed as a treatment for various problems in persons who do not have vitamin B6 deficiencies, including for treatment of autism. The clinical results of such treatments are variable.
- Administering high doses of vitamin B6 (pyridoxine) and magnesium is not recommended as an intervention for autism in young children. [C]
- Administering high doses of any type of vitamin or trace mineral is not recommended as a treatment for autism in young children. [D1]
- If a child with autism has a documented vitamin or trace mineral deficiency, it is recommended that this be treated as appropriate. [D2]
The proposed theory for linking autism to food allergies
Diet therapies, especially those that involve the elimination of cow's milk products (containing casein) and/or wheat products (containing gluten) from the diet, have been proposed for the treatment of autism in children. Proponents of these diets suggest that autism in some children is related to allergies to specific foods, and that eliminating these foods from the diet can result in an improvement in manifestations of autism.
Diet therapies are not generally accepted as standard forms of treatment for autism and are considered experimental by many experts. The theory that food allergies might cause or contribute to autism is controversial. It is also controversial whether food allergies are more common in children with autism compared to children without autism.
One theory why certain food may contribute to autistic manifestations suggests that certain food proteins break down in the stomach to chemicals that resemble opiates (that is, morphine-like chemicals). Proponents of this theory suggest that children with specific food allergies will develop higher blood levels of these morphine-like chemicals after eating foods they are allergic to. This in turn is postulated to cause an increase in autistic behaviors and other manifestations.
- The use of special diets that eliminate milk-products, gluten products, or other specific foods from the diet is not recommended for the treatment of autism in children. [D1]
- If food allergies are documented in a child using standard allergy testing methods, then appropriate dietary changes or other treatment may be needed, but this would be unrelated to the child's autism. [D2]
- Allergy testing (using either intradermal testing or blood tests for specific antibodies) provides no information that is either helpful in determining appropriate treatment for autism or useful for predicting or measuring functional outcomes for children with autism. [D1]