Medications on the market are approved by the Food and Drug Administration (FDA; www.fda.gov) for a specific purpose: depression, anxiety, schizophrenia. Once a medication is on the market, health care providers can use it for purposes other than those for which it was approved. The term off-label use refers to the practice of using the drug for a condition outside of the approved use. In other words, once a drug has been approved by the FDA, it is up to the people who prescribe medications to use good judgment in prescribing. Off-label use of medicines is very common—possibly 50% or more of medicines used in pediatrics are given for off-label uses. This is a real problem in pediatrics in general, and in autism in particular, and reflects several different problems—difficulties in doing research in children, particular difficulties in doing research with children with disabilities, and a lack of incentives and/or requirements for testing medications in these populations. Thus, given the lack of research on medications for children with autism, it is often the case that the medicines being used are “off label.” In contrast to off-label uses, in 2006 the FDA approved the use of risperidone for the treatment of tantrums, aggression, and self-injury in children with autism. However, many of the drugs commonly given to children with autism for behavioral and emotional problems may not have been studied or approved by the FDA for use in children with autism (or in any children, for that matter).

The doctor may discuss the complexities of all this with you, but you should realize that “off-label” use of medications is quite common—really the rule, rather than the exception. Discussion with the care provider should focus on matching the target problem with the medication.

RESEARCH ON MEDICATIONS

DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES

Groups of individuals are studied with careful attention to scientific controls, such as randomly dividing individuals into groups. One group (the control group) might receive a placebo or nonactive substance, while the other group might receive the active medication. Neither the child, parents, nor doctor giving the medicine know what group the child is in, hence the term double-blind). There are many advantages to this kind of study.

• The data that are collected can be analyzed free from the potential bias that goes with an unblinded study.

• In the variation on this method called the crossover design, children might be treated with a placebo for some weeks and then started on the active medicine or vice versa, giving all participants the opportunity to try the treatment being studied.

• Limitations: Although controlled studies are the most effective ways for giving us good information, they are the most costly to do.

OPEN-LABEL STUDIES

In these studies, the treatment is administered to many people, and everyone involved knows what medication is being studied, hence the term open-label.

This kind of study has some advantages, particularly when a medicine is first being used.

• Groups of individuals are studied (more powerful than studying just a few people).

• The study may provide information about who does and doesn’t respond and what the side effects are.

• Limitations arise because the study is open (or technically what is termed nonblinded), so things like the placebo effect can cloud the results. Placebo effects can be substantial; for example, sometimes up to 20% or 30% of patients will improve on placebo.

CASE REPORTS

These are written accounts of individual patients’ responses to a treatment; sometimes results are collected and reported with objective, scientific rigor, but sometimes the report may be more casual or even biased, whether intentionally or unintentionally.

• Studies of this kind often provide the first clues that a drug may be effective for a problem.

• They are severely limited by:

• Concerns about whether the children studied actually had the disorder (e.g., autism) to begin with

• The possibility that lack of a good control group/condition and the “placebo effect” may make the medicine look more effective than it will be in subsequent studies

• The possibility that gains made may not last

What Is the Placebo Effect?

The placebo effect refers to the many important benefits of being involved in research, whether or not the child is receiving the treatment being studied or a placebo (inactive medication). These effects all can make a major change (for the better) in the child. The first question to ask is why children get better on placebo. There are several answers to this question:

• Research involves high levels of clinician, parent, and teacher involvement, and more attention and interest may help the child improve.

• Every effort is made to provide high-quality care during a study.

• Symptoms change over time (often, people try something new, such as volunteering for a research study, when things are at their worst and the only way for things to change at that point is for them to get better).

• The effects of expecting a change for the better can be important; for example, expectations for improvement change how a parent or teacher observes and interacts with the child.

Developing a Treatment Plan

If you plan to pursue drug treatment for the child’s behavioral or emotional problems, you should work with a physician or other health care provider who is knowledgeable about the use of these medicines (and their side effects). This provider (who may be a psychiatrist or child psychiatrist or sometimes a pediatrician or neurologist, or nurse practitioner) will want to meet with you and the child. During this meeting, the doctor, or sometimes another health care provider, will take a history of the problem as well as a more general history of the child. This will typically include the child’s birth and developmental history, results of any previous evaluation, the child’s medical history, previous drugs used (if any), and the child’s response, as well as any relevant family history. This history may be important, because conditions such as depression and other mood disorders can run in families. Any history of unusual responses to medication, drug allergies, and similar information will also be reviewed. The doctor will want to spend some time with the child and may want to see the child in his classroom or talk with school staff (obviously, with permission from the parents).

The doctor will tell you about the pros and cons of various options and develop a treatment plan. Depending on the kinds of medicines that are being discussed, some baseline lab tests (e.g., of the blood or urine) might be obtained. Before beginning some medicines, the doctor might want the child to have an electrocardiogram (ECG). For other medicines, periodic blood tests might be needed to monitor the level of the medication or to look for possible negative side effects. If the doctor prescribes medication for the child, he or she should tell you:

• The name or names of the medication

• What the expected benefit is

• What the possible adverse effects and risks are

• How the medicine is monitored and the dose is adjusted

• When you should see a change, and what to do when you see a change

Some clinicians may ask you to sign something to document, for the record, what you have actually discussed. If appropriate, the child (particularly if an adolescent or young adult) should be involved in this discussion.

The child’s primary care physician should always be kept informed about the child’s medication(s). This is important because it is this person who knows the child’s medical history best. In some cases, you may see a specialist some distance away for a consultation, but the local primary care provider may be willing to prescribe the medications as long as the specialist is available for backup. Depending on the nature of the child’s problems and other aspects of the situation, it may also be advisable to inform school staff such as the classroom teacher and school nurse that the child is receiving medicine. This is mandatory if the child is to receive medicines during the day at school. Schools may have their own requirements about documenting medicine, and the staff may be helpful in documenting how well the medicine is working and in observing side effects.

Understanding Potential Side Effects

All drugs have at least some potential adverse effects. This is true for medications as simple as aspirin! Sometimes side effects are related to dose and are more likely at higher doses. Other times, side effects may occur regardless of the dose, as is the case with true allergies to medications. Side effects vary from medicine to medicine. Sometimes side effects can be something that may help; for example, some medicine might have some sedative side effect that might help with getting to sleep. Technically, the term adverse effects is more frequently used to refer only to side effects that are unwanted. In the discussion of medicines later in this chapter, we mention some of the main side effects seen with different groups of medicines. A child may not have any of these side effects. However, the child may have some side effects we don’t list. Sometimes side effects are seen right away; other times, they can take a while to develop. Some side effects might be seen early on but then tend to go away with time.

All of this means that when parents discuss medicine for behavioral or emotional problems with the doctor, they should be sure to get a good sense of the more common possible side effects, as well as the rare but more worrisome side effects. Based on the side effects reported to the doctor, she or he may want to change the dose, switch to a new medicine, or even add a medicine that will help with the side effects or further strengthen a positive response.

DO’S AND DON’TS FOR PARENTS

Parents play an integral role in working with the prescribing clinician to ensure their child is benefiting from medication and receiving the optimal dose. Here are some do’s and don’ts to pay attention to, whenever the child starts taking a new medication.

DO:

• Have a detailed discussion with the doctor prescribing the medication about exactly what you can expect: the possible benefits and risks, how long it might take to see results, how the doctor will monitor the medicine, how often you will see the doctor.

• Ask why the doctor favors one medicine over another and what form the medicine is in (pills, capsule, liquid).

• Make sure you understand when to administer the medication and what to do if the child misses a dose.

• Ask if there are reasons to call the doctor right away and how you can get hold of him or her if there is an emergency.

• Ask how you can help determine whether the medication is helping the child. Is there specific information you (or the school) can collect? What kind of information should you track, and how often should you record it? How can you best record this information and get it to the doctor?

• Be sure the child’s primary health care provider is “in the loop” and knows why the medicine is being prescribed and what the side effects might be.

• Ask the primary care provider if you need any blood tests or other medical tests before you start the medication. Remember, your child may be much more comfortable having blood taken in a familiar office than a strange place.

• Use the same pharmacy for all the child’s prescriptions. This helps ensure that the pharmacist will notify you and the doctor if there is any potential for medicines to interact with each other.

• Let the doctor and pharmacist know if the child is taking vitamin supplements, herbal treatments, or any other nonprescription remedies that could affect the way medication works.

• Be a careful observer of the child; often, you’ll notice changes before other people do.

DON’T:

• Pretend to be a doctor—ask for help if you need it.

• Stop the medication without asking the doctor first. Many medicines must be slowly discontinued (tapered) and not stopped abruptly.

• Give up too quickly. Some medicines can take weeks or months to work.

• Stop behavioral or educational interventions when you begin a new medication.

• Try to do a lot of new things at the same time as beginning a new medicine. This complicates figuring out what accounts for any improvement.

MEDICATIONS USED IN AUTISM AND RELATED CONDITIONS

The following sections provide some basic information on the major classes or groups of medication sometimes used in treating the behavioral difficulties of children with autism and other pervasive developmental disorders. In each section, there is a short description of what we know about how the medication works and what it seems most useful for. The most common adverse effects of the medications are discussed, and we give some examples of medications in this group. Please remember that this is a selective and not an exhaustive list of medications. Also keep in mind that we provide only a short description of some of the more common side effects and that many others are possible. If you are considering a trial of medications, you need to have a detailed discussion of the potential benefits and risks as they apply to the child. That is, the discussion should take into account all the information relevant to the child such as his medical history, family history, previous response to medications, and so forth.

The reading list at the end of the chapter provides some reference to fairly detailed books on medications written for parents, teachers, and other nonphysicians. You may want to look at these. Some excellent books (written specifically for medical professionals) are also available, and some of these are included in the reading list as well. Given that this is an area where, fortunately, more research is going on now, parents and others may wish to check online resources like PubMed (www.pubmed.gov) as well.

With a few notable exceptions (discussed later), most of the information available to us on medications for treating behavior problems is, unfortunately, rather limited. Mostly, we are relying on case reports and studies of series of cases rather than on well-controlled, double-blind studies. Fortunately, more research is now being done on these medicines, and new knowledge will be coming out at an increasingly rapid pace. Although the information we provide here is up to date at the time of our writing, keep in mind that new studies are always being conducted and information may change—another reason to work with a professional who keeps up with new developments.

Major Tranquilizers (Antipsychotic Medications)

The medications most often prescribed to treat behavior problems in autism are called major tranquilizers. These medicines were some of the first medicines developed 50 years ago in psychiatry specifically for treating schizophrenia, hence the name antipsychotic. There is more research on them than on other classes of drugs. Some newer, second-generation antipsychotics in this group have been developed in recent years and lack some of the side effects of the older medicines in this group. These medicines are often used when children have significant problems with self-injury, stereotyped behaviors, aggression, and irritability. They are sometimes used for children with high levels of activity or behavioral rigidity.

The antipsychotics seem to have a major effect on the brain systems that involve dopamine, one of the messengers (neurotransmitters) between nerve cells. To varying degrees, these medications act in some way to block the effects of dopamine in the brain. They also have effects on other chemical systems in the brain. These various effects account for the desired—or positive—effects, as well as the adverse effects of medication. The brain chemical dopamine appears to be involved in some way in certain behavior problems in autism, for example, the self-injurious behavior and stereotyped or purposeless repetitive movements. Sometimes low doses of antipsychotics effectively increase the attention span of children with autism and help them to learn more effectively. This is not usually why antipsychotics are prescribed for children with autism. But it is an example of how side effects can actually be a good thing once in a while.

Usually, the dose is started at a very low level and gradually increased. The effects of the medicine can be relatively rapid. Occasionally, a higher dose may be used to start. This is mostly done in emergency situations.

We’ll start our discussion with the newer of these medications; these are the ones most commonly used today. Then we’ll discuss some of the older medications in this group; these are now less commonly used.

Second-Generation Antipsychotics Second-generation antipsychotics (see Table 15.1) are a relatively new group of medicines, which have attracted much attention because of their greatly reduced risk of a side effect called tardive dyskinesia. This term literally means a slow to develop movement disorder and is a side effect that occurred more frequently with the first generation of drugs. These newer medicines, sometimes called atypical antipsychotics, also seem to be more effective in helping with the social withdrawal and lack of motivation in adults with schizophrenia (which may or may not have much to do with the social problems in autism). Additionally, these medicines seem to help with agitation, temper tantrums, aggressiveness, self-injury, high activity levels, and impulsivity—the same problems that the older “first-generation” neuroleptics were used for. One large, double-blind, placebo-controlled study of these medications has shown them to be effective in children with autism.

TABLE 15.1

SELECTED SECOND-GENERATION (ATYPICAL ANTIPSYCHOTICS)

The atypical neuroleptics are largely replacing the older, first-generation medications, in part because of the lower risk of serious side effects. Still, there is a variety of side effects, which can include sedation, movement problems, weight gain (with the possible exception of ziprasidone), changes in the ECG, and possibly diabetes.

One of the first drugs in this group, clozapine, can have some major side effects, including reducing the white blood count. Consequently, it is not used as frequently as the others and has not been as intensively studied in autism.

Another of these medicines, risperidone, has been very well studied and is now approved by the FDA for the treatment of aggression, tantrums, and self-injury of children with autism ages 5 to 17 years. One of the studies that contributed to approval of risperidone was a trial by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. In this study, children with autism and serious behavioral problems were randomly assigned to an 8-week double-blind trial of either risperidone or placebo. The children in the risperidone group had a large and significant reduction in these serious behaviors and were more likely to be rated as much or very much improved by clinicians who did not know whether the child was on the active medicine or placebo. There were some minor side effects of risperidone (fatigue, drooling, drowsiness), most of which passed quickly. The major side effect was weight gain (2.7 kg or almost 6 pounds on average).

In a second part of the study, children were followed over time in an open-label study (i.e., there was no longer any attempt to keep up the double-blind part of the study). Children who responded well to risperidone continued to do so at a low to medium dose level. After 6 months, children were then randomly assigned to a discontinuation trial (some children stayed on the active medicine; others gradually switched over to placebo). As with the first phase of the study, the discontinuation was double-blinded. Only a few children tapered off the medicine successfully; most had the return of behavioral difficulties and went back on the risperidone. The response to risperidone in this study was larger than the response to the first-generation antipsychotics in older studies. Although there were many fewer side effects overall, weight gain emerged as a common problem. It is worth noting that sometimes weight gain can be substantial, and it may not be easy for a child to lose the extra weight even after the medicine is stopped.

There have been studies of other atypical antipsychotics as well, although they have not been as well studied as risperidone. In particular, olanzapine has shown some potential to reduce irritability, aggressiveness, overactivity, and obsessiveness in open trials. Weight gain seems to be an even bigger problem with olanzapine. Some parents don’t mind the weight gain (particularly if their child is on the thin side). However, substantial weight gain can be a problem for many children with autism, who may not get enough exercise anyway.

First-Generation Antipsychotics Because these medicines have been around longer, they are often called first-generation antipsychotics. These medicines are often used for treatment of severe behavioral difficulties such as aggression and self-injury, as well as agitation and stereotyped movements. Some of these medicines have been studied in controlled, double-blind trials in autism. A few trials have followed children for several months. Improvements have been documented in such areas as agitation, withdrawal, and self-stimulatory movement. Many children respond well to these medicines.

In general, children should be prescribed the lowest possible dose of these medications, as some of the side effects occur more often at higher doses. (See the section on side effects later in the chapter.) These medications are more likely to make the child feel drowsy or sleepy (some cause more sedation than others). Sometimes sedation is mistakenly viewed as a positive response. That is, the child is no longer making much trouble. However, the child may also not be doing much learning!

There are a number of medicines in this group. Haloperidol (Haldol) is one of the more potent members of this group and is the most well studied in children with autism. It can be effective in reducing high levels of activity, agitation, and stereotyped or self-injurious behavior. Studies of Haldol have demonstrated that it works quite well in children affected with moderate to severe autism. Significant behavioral improvement may occur at relatively low doses. Side effects are observed but are not usually common at low doses. It is usually started at a low dose and gradually increased. When effective, usually there are periodic attempts to lower the dose of medication. It is important that such drug “holidays” be planned to ensure that children receive the lowest effective dose of medication. At very low doses, haloperidol is not usually very sedating, but at higher doses, it can be.

Another medicine sometimes used in treating children with autism is chlorpromazine (Thorazine). Thorazine is a low-potency antipsychotic; that is, a higher dose needs to be taken to achieve the same effects as with a high-potency medication such as Haldol. For example, about 100 mg of Thorazine equals about 1 mg of Haldol in terms of effectiveness. It’s important to realize that the differences in potency in this and other groups of medications can make it difficult for anyone other than a professional to evaluate how high or low a dose of medication actually is. Thorazine is much more sedating than Haldol. This can be a benefit for some children; however, sedation is often a problem, but sometimes this can be avoided by giving a larger dose before bedtime, when it may help the child get to sleep.

In between Haldol and Thorazine, there are a number of other medications (see Table 15.2). These tend to be intermediate in terms of potency and their side effect profile. Some of these medicines come as capsules or tablets and some are available in liquid form; this can be important if the child has trouble taking pills.

TABLE 15.2

SELECTED FIRST-GENERATION ANTIPSYCHOTIC MEDICATIONS

Adverse Effects Side effects of antipsychotics include a group of neurological abnormalities. These symptoms can include stiffness in arms or legs, shaking of the fingers or hands, restlessness (akathisia), stiffness of the neck, and unusual movements of the head and eyes. These problems often appear in the first weeks or with dose increase. These neurological adverse effects are called dystonias (muscle stiffness), and dyskinesia (disordered movements). These can sometimes also be seen when the medicine is discontinued or reduced (withdrawal dyskinesia).

The restlessness and some of the motor movements associated with these medications can be treated with other medications such as benztropine (Cogentine) or diphenhydramine (Benadryl), which can be given along with the major tranquilizer. Some doctors use these additional medicines almost routinely to try to prevent any of the acute movement problems.

Sometimes, a movement problem called tardive dyskinesia occurs. This movement disorder usually develops after months or even years of treatment, but sometimes more quickly. It takes the form of various involuntary movements of the body extremities; neck; or the face, mouth, and tongue, and may be associated with what appear to be grunts or tics. This condition can be confusing because at times it resembles the kinds of motor mannerisms frequently seen in autism. It is important to note that reducing the dose of medication may seem to make the tardive dyskinesia even worse.

Because tardive dyskinesia is sometimes reversible, doctors should screen for it when they begin treatment with antipsychotics and as they follow a child who is treated over time. That way, if there are early signs suggesting tardive dyskinesia, the medicine can be stopped. There are specific rating scales that doctors and nurses can use to monitor the unusual movements sometimes associated with these medications.

Occasionally, when a medication is discontinued or reduced, withdrawal dyskinesias occur; that is, the child begins to exhibit some unusual movements. These usually persist for only a few weeks but may be disturbing to parents and children. Adolescents and adults appear to be more likely to have these than young children. The risk of withdrawal dyskinesia increases if the medication is stopped abruptly rather than being slowly tapered.

Other side effects sometimes observed in first-generation antipsychotics include true allergic reactions (not just motor side effects), which can cause serious medical problems. True allergic reactions can include breathing problems, hives, and other skin symptoms, and are a serious medical problem. Sometimes parents will say that their child had an “allergy” to a medicine when what they really mean is that he or she didn’t do well with it or had some other side effects (not really allergy). It is important for parents not to call other types of side effects allergies. Sometimes you can inadvertently confuse a doctor by telling her the child had an allergy to a medicine when you really mean he had a side effect of some kind, and not a true allergic reaction.

As a group, these medicines tend to have some of the same side effects as “cold pills,” such as dry mouth, constipation, and so forth. Because these drugs are metabolized in the liver and other parts of the body blood tests are periodically used to monitor liver, kidney, and other functions. In addition, many of these medicines in this group have a tendency to increase the likelihood of seizures in children with epilepsy (Chapter 12). Thus, their use should be considered carefully in a child with a seizure disorder. Furthermore, many of these medications can cause some degree of weight gain. Finally, individuals taking these medications (especially in high doses) need to be careful not to become too hot. A rare condition (malignant hyperthermia) can occur in children whose temperature increases dramatically. Children on these medications should be encouraged to drink a lot of fluids, particularly in the summer.

Again, it’s important to keep in mind that adverse effects are often dose related; that is, they are more likely with higher doses of medicine, but sometimes they can occur at low doses.

Medications for Attentional Problems

Stimulant medications are very widely used in the United States for treatment of attention deficit hyperactivity disorder (ADHD). It appears that these medicines work by increasing levels of a brain messenger chemical called dopamine. (Note that this is different from antipsychotics, which block dopamine in the brain.) Stimulants help the child to focus, attend, and be less restless. These medicines are very effective in individuals with ADHD; probably helping about 75% of those diagnosed with the disorder (see Table 15.3). There are also some nonstimulant medications used to treat attentional problems although the stimulants are still the most widely used.

TABLE 15.3 SELECTED MEDICATIONS FOR TREATMENT OF ADHD

There are many different types of stimulant medications. They differ from each other in some ways. For instance, some are longer acting than others, and some tend to be associated with different side effects. Side effects of these medicines in children with ADHD include irritability, occasional worsening of hyperactivity, sleep problems, and decreased appetite. Occasionally, children have problems with dizziness and sometimes seem to become more moody or agitated. Children taking these medications sometimes develop tics (rapid, repetitive movements often involving the head and neck and upper body), or, if they have very mild tics, these can get worse. Other side effects can include other habit problems (picking their skin) or, more rarely, hallucinations.

Stimulant medications are among the more commonly used in children with ASDs for the same reason they are used in children with ADHD: to help increase attention and decrease hyperactivity and decrease impulsivity.

Until recently, there were few studies of stimulant medications in children with ASDs. The few studies that were done included only small numbers of children. As is often the case, results of these small studies don’t agree simply because the samples were not comparable. The RUPP Autism Network completed a large-scale trial using three different doses of methylphenidate (Ritalin) and placebo. The trial used a so-called crossover design so that each child took the low dose, the medium dose, the high dose, and placebo in alternating weeks. The medication was disguised to make sure that each dose and placebo was blinded. Parents and teachers scored the behavior every week. The results showed that each active dose was better than placebo. But only about 50% of the children showed improvement. This rate of positive response is much lower than the positive response rate in the 75% of children with ADHD but not autism. The adverse events were similar to what we see in children with ADHD, but these adverse events were more common in the children with ASDs. The RUPP group looked closely in order to identify which subjects were more likely to show a positive response. There is some evidence that children with normal or near normal intelligence quotient (IQ) are more likely to show a positive response. But no other subgroups (e.g. autism, Asperger’s, or PDD-NOS) were more or less likely to show a positive response to methylphenidate. Although stimulant medication can help to reduce hyperactivity and improve attention, these medications may not help other problems, such as anxiety, depression, or compulsive routines or rigidities. Then the question of adding a second medicine to deal with those problems may come up (we’ll return to this topic toward the end of this chapter).

When stimulant medications do work, they should be monitored over time. Given the medications’ potential to decrease appetite, the pediatrician will want to monitor the child’s height and weight every 4 to 6 months or so. If there are problems with growth and weight gain, you can try lowering the dose, using drug holidays, or switching to a different class of medicine. Medications such as atomoxetine (Strattera) or guanfacine (Tenex) can also be used to treat hyperactivity. As the child grows older (and if the medicine is still needed), the dose can be adjusted. It is also important to make sure the child still really needs the medication by occasionally having a drug holiday—planned periods off medication to reevaluate the benefit. These trials off medication should be done in close collaboration with the primary care provider or mental health clinician.

Antidepressants and Selective Serotonin Reuptake Inhibitors

Antidepressants and the chemically related SSRIs were originally developed for the treatment of depression and/or obsessive-compulsive disorders (OCDs). There are several antidepressant medications on the market (see Table 15.4). These medications differ according to the brain chemical systems they affect. The most common type is the so-called selective serotonin reuptake inhibitors (SSRIs), which prevent (inhibit) the reabsorption (reuptake) of serotonin after it is produced in the brain, thereby increasing the level of serotonin in the brain. SSRIs are quite selective in how they act on serotonin; that is, they have little, if any, effect on other brain chemical systems such as norephinephrine and dopamine. There is also one medicine in the group (clomipramine [Anafranil]) that is less selective but still a potent reuptake inhibitor of serotonin (technically an SRI rather than an SSRI). Because SSRIs are used more frequently, we’ll discuss them first.

SSRIs have attracted much interest for autism based on the assumption that these medicines could be useful in treating the prominent behavioral rigidity, ritualistic behaviors, and rituals commonly seen in autism spectrum conditions.

TABLE 15.4

SELECTED ANTIDEPRESSANTS AND SEROTONIN REUPTAKE INHIBITOR MEDICATIONS

A number of studies, not always well controlled, have looked at how well the SSRIs work in autism. In general, these early studies have been encouraging, with many individuals responding positively, but research is still in the early phases. One complication is that—for some reason we don’t understand—there seems to be a lot of variability in how individuals with autism respond. Some children respond well to a lower dose than a slightly higher dose; others to one of these medicines but not another. It does seem that adolescents and children who are nearing adolescence respond better than younger children.

Although initial studies and clinical experience showed some promise for SSRIs on these outcomes, more recent studies have not been so positive. The earlier studies were small and the clinical target(s) for the medicine not always so clear. A recent federally funded study with a large sample of children (5 to 17 years of age) was conducted at six different medical centers. One of the SSRIs was studied in terms of its effects on repetitive behaviors and other symptoms. In this placebo-controlled study, after 16 weeks the group treated with the SSRI was no better than the placebo group but did have more adverse effects: sleep problems, overactivity, talkativeness, and impulsivity (this combination of adverse effects is often called activation and is sometimes seen with SSRI treatment). The results of this study have challenged the widespread use of SSRIs, although, clearly, other conditions such as depression or clear-cut OCD might be improved.

If the child is prescribed an SSRI, you will need to work fairly closely with a psychiatrist or other health care provider. First, because of the variable response in children with ASDs, the first SSRI you try may not be the most effective one. Second, it takes a relatively long time (weeks) to get the dose to a reasonable level and determine how effective the medication is for the child. When stopping these medications, they should generally be gradually tapered. This is because some children may have a kind of withdrawal reaction to stopping too quickly, which can include nausea and vomiting, abdominal pain, headache, and other reactions. Before starting either SSRIs or antidepressants, the child should have a medical history and physical exam. As noted earlier, treatment with clomipramine requires an ECG before and during treatments, as well as blood tests for drug levels. The antidepressant bupropion (sold as Welbutrin, Zyban, and Budeprion) should not be used in individuals with epilepsy (seizure disorder).

Another important consideration with the use of the drugs is the possibility of drug interaction. This can happen several different ways. For example, fluoxetine (Prozac) and citalopram can slow down the metabolism of other medications; this can actually result in an increase in levels of medicines (e.g., risperidone, and may increase the likelihood of adverse effects). To deal with this possibility, clinicians usually move even more slowly than usual if combining medications. Other antidepressants, notably clomipramine, are vulnerable to drug interaction. Because high levels of clomipramine can be toxic, it is important to be very careful. Commonly used medications such as erythromycin or even grapefruit juice can retard the metabolism of clomipramine and cause levels to rise. The important point is that all the prescribing care providers need to be aware of the medicines the individual is taking and to warn about possible drug interactions.

Mood Stabilizers

As you would expect from the name, the medications in this group all help to level out or stabilize mood disorders. The classic example of a mood disorder is something called manic-depressive illness or bipolar disorder. Individuals with bipolar disorder have major swings in mood. For instance, they may have periods (weeks to months) of serious depression followed by periods of having a normal mood and then by periods of elation and mania. The adult forms of the mood disorders are more straightforward to diagnose than the forms seen in children. In children, irritability, overactivity, and aggressive behaviors may signal a mood disorder or reflect severe disruptive behavior. The up-and-down cycle of mood disorders can be a bit more difficult to see in children.

There has been some speculation that mood disorders may be increased in children and adolescents with PDD. These issues are somewhat controversial, given that, for example, irritability and overactivity are often seen in children with PDD.

TABLE 15.5 SELECTED MOOD STABILIZERS

In strictly diagnosed autism, the general response to mood stabilizers is not usually positive. However, these medications may be helpful if the child has symptoms suggesting that an additional diagnosis of bipolar disorder or other mood disorder is justified, particularly if there is a family history of mood disorders. Children with cyclical patterns of mood problems and irritability associated with insomnia and overactivity may also be candidates for mood stabilizers. We have seen a few patients who have responded positively to mood stabilizers. These children had clear evidence of cyclicity in behaviors (swings from good weeks to weeks when the child’s behavior was more out of control), and often there was a member of the immediate family who also had a mood disorder.

Medications used to treat mood disorders (see Table 15.5) include lithium and some of the same medicines used to treat seizures (anticonvulsants). The precise way these medicines work is not known. Lithium is probably the most well known of the mood stabilizers used with adults, although anticonvulsants are more frequently used now and are more likely to be used in children.

There are some studies of anticonvulsants for mood problems in children with autism, but these are mostly reports of single or a few cases and tend not to be of the most rigorous quality. More research is clearly needed. Some of the medicines used to deal with cycles in mood associated with overactivity and insomnia include carbamazepine and valproate (valproic acid), and also sometimes lamotrigine. In children with ASDs, problems that have reportedly improved on such mood stabilizers include mood problems, impulsivity, and aggression.

When anticonvulsants are used as mood stabilizers, levels of medicine are monitored through regular blood tests, to be sure that both an effective or therapeutic level of the medicine is reached and the level does not get too high. Typically, a child is put on a medicine for several days, before the first blood level is taken. The blood level is usually taken about 12 hours after the last dose (usually first thing in the morning before the child takes the morning medication).

Various medical tests are usually done before starting treatment with mood stabilizers. Depending on the medication, these may include tests of the kidney and thyroid (particularly if lithium has been prescribed), as well as tests of the liver and blood counts for some of the other medicines.

Side effects of mood stabilizers can include sedation, changes in the blood count, and liver toxicity. Lithium can affect thyroid and kidney function and lead to a fair amount of weight gain over time. (Because of concerns about lithium’s side effects, it is used less often than some of the other mood stabilizers but can still be used for children with major mood problems.) The doctor should discuss all the potential side effects with you.

Medicines to Reduce Anxiety

All of us have experienced anxiety. Anxiety can serve a useful function, such as reminding us of dangerous or risky situations. Sometimes, however, anxiety becomes a problem that needs treatment, for example, if someone is immobilized by chronic anxiety or has panic attacks or specific fears that make it difficult to function in the day-to-day world.

Children with ASDs also can have problems with anxiety. Sometimes this seems similar to the kinds of anxiety that others of us experience in confronting frightening or stressful situations. Other times, the anxiety in autism is highly unusual and may be more related to difficulties in dealing with new situations or certain problem situations.

The medicines used in treating anxiety problems for typically developing children, adolescents, and adults can sometimes be successfully used in treating serious anxiety problems in children with autism spectrum conditions. However, as we will discuss shortly, there has not been much research on using these medicines in autism. In addition, sometimes the same medicines that seem to help the rest of us relax can make children with autism worse, that is, more agitated and disorganized.

Several different groups of medicine can be used to reduce anxiety (see Table 15.6). Some of them may be familiar to you because you or someone else in the family has used them for anxiety (e.g., lorazepam [Ativan]). Others in this group may be less familiar. We’ll discuss each group briefly.

Benzodiazepines The benzodiazepines have been widely used in adults and typically developing children to help deal with anxiety specific to situations, for example, before the person goes for dental work. However, these medicines have not been well studied in children, and even less so for children with ASDs, but they can be useful at times. Common benzodiazepines include diazepam (Valium) and (lorazepam) Ativan.

TABLE 15.6 SELECTED ANTIANXIETY MEDICATIONS

Occasionally, children including those with developmental problems become somewhat more agitated on these medicines (this is called paradoxical agitation). If, for example, the dentist suggests that you try one of these medications to help calm the child during a dental procedure, you may want to try a test dose at home first to judge the child’s response. There are some alternatives for sedation when these medicines don’t work. For instance, occasional Benadryl works well in some children. You can also discuss other alternatives with the health care provider.

The benzodiazepines are habit forming and should not be used in an open-ended way. However, if these medications do work for the child, they can be valuable when used on an occasional basis for situations you know will make the child very anxious. They should not be mixed with alcohol, since they each can make the effects of the other stronger. As when trying any new medicine, discuss with the doctor and/or pharmacist the other medicines the child is taking.

Beta Blockers Another group of medicines called beta blockers are sometimes used for children with autism and related conditions. These medicines were originally used as blood pressure medicines, but are now also used to deal with anxiety and irritability. There have been some open-label studies and case reports of beta blockers in the treatment of anxiety, but good double-blind studies are not available.

These medicines have a number of potential side effects, and it is important to weigh the pros and cons seriously before starting them. Side effects can include low blood pressure and problems with heart rate. These medicines can also make asthma worse. You have to be careful to take the medicine as prescribed and taper when the child is through with it. In general, these medicines have to be taken chronically (all the time) to work.

Alpha-Adrenergic Agonists Another group of medicines that were first used to lower blood pressure are sometimes used to treat behavioral problems. These medicines, called alpha-adrenergic agonists, work through a different system than beta blockers and can help in the treatment of tics (unusual, recurrent impulsiveness and distractible movements). For some children, they can also improve problems with overactivity. They are sometimes recommended for children with autism, particularly for children who are hyperactive and impulsive. The data on using these drugs for ASDs are limited, but they are commonly used in children with other conditions such as Tourette’s syndrome and ADHD.

Clonidine (Catapres) has been used to treat tics as well as attention problems; a similar medicine is guanfacine (Tenex). The medicines are given in divided doses by mouth. (Clonidine also comes in a patch formulation.)

Because these medicines are also used to control blood pressure, they can lower blood pressure (hypotension) and heart rates. Occasionally, children may develop what is called orthostatic hypotension, or low blood pressure when standing up, which can cause dizziness. In addition, these medications can cause sedation, either at the start or over the long term. If sedation is a problem, the medication can be given mostly at night to help with sleep. Some children may fall asleep without difficulty, but may wake up during the night. This can usually be handled by adjusting the dose. It is particularly important that they be given as prescribed and tapered off slowly if they are discontinued. (Blood pressure can rapidly increase if these medicines are stopped too quickly.) Sometimes tolerance to the medicine seems to develop.

Opiate Blockers There has been some speculation that some of the self-injurious behaviors in autism may be designed to induce the release of opiate-like compounds in the brain. The theory runs like this: Perhaps when individuals hit themselves or engage in other self-injurious behaviors, they generate a kind of natural “high” (similar to a “runner’s high”) because their bodies are producing a kind of internal opiate (like opium). If so, perhaps the same medicines that are used to block the effects of externally produced opiate (i.e., opiate drugs, such as heroin) might also serve to undercut this effect and thus eliminate or reduce the behavior. Another theory is that individuals with autism have a very high pain threshold and that self-injury is a form of self-stimulation. A small number of studies have raised the possibility that individuals with autism have higher natural levels of endorphins (the opiate-like compounds the body naturally produces). If so, it could be that self-injury is, paradoxically, an attempt by the child to make himself feel better.

Two different drugs that are ordinarily used to help people with opiate drug overdose problems have been used in children with ASDs: naloxone (Narcan) and naltrexone (Trexan). Since naloxone has to be given intravenouly, naltrexone has been more extensively studied in autism. Studies were conducted starting in the late 1980s and continuing through the past 10 years. Initial studies tended to be small case reports. As often is the case early on, initial results were encouraging. Unfortunately, double-blind studies have not shown the same positive picture. Now most of the apparent benefit appears to be in reducing hyperactivity. (Again, this is a reminder of why it is so important to conduct double-blind studies.) There is some suggestion that this group of medicines may cause worsened troubles in children with Rett’s disorder. Side effects of these medicines include, notably, nausea and vomiting. At the moment, these medicines do not seem to have major usefulness in children with autism.

Combining Medications

Children with ASDs often end up being given more than one medicine for their emotional or behavioral problems. This practice, referred to as polypharmacy, is a complicated one. Sometimes two medicines are given because one is controlling side effects of the other. Sometimes a second medicine is added after a first one seems to work a bit but not as much as is wanted. Occasionally, taking two medicines together may mean that a lower dose of each can be used. Sometimes one medicine, which acts more quickly, may be given while a longer-acting medicine is being introduced. Sometimes the doctor will feel that two conditions are really present and consider using two medications to treat them. (We have discussed comorbidity on page 454.) These are just some of the possible reasons for giving more than one medicine at a time.

Unfortunately, there are a number of potential problems with taking multiple medicines. One is in sorting out which medicine is doing what; in other words, how can you tell which medicine is being most helpful? In addition, there is always a trade-off when using more than one medicine. For example, there may be more potential for side effects and more hassle in giving more than one medicine. Furthermore, the potential for drug interaction clearly increases, and it is important that the pharmacist and regular health care provider are aware of all the medicines the child is taking. Finally, some combinations of medicine clearly don’t work and might be more risky than taking one medicine.

Occasionally, we have seen children with autism on many different medicines at the same time (the record is about 10) with the idea that each medicine is treating a different thing—anxiety, depression, attention, and so forth. In these situations, the child’s behavior often deteriorates and it is impossible to figure out why and what to change. In general, with some exceptions, it probably makes sense to start with one medicine.

If the child’s doctor discusses adding a second medicine, you should feel like you understand why he or she is recommending this. If things start to get very complicated and you are giving the child many different medicines, it may be time to step back and think about getting another opinion.