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Pharmacological treatment options for autism, Part 2. (EP On Autism).

Overview of Medications

In the first part of this series, we focused on using neuroleptics to treat autism spectrum disorders. In this part, we will examine three other major groups of medications: anti-depressant/ anti-anxiety agents, stimulants and anticonvulsants.

Anti-Depressant and Anti-Anxiety Agents

Serotonin re-uptake inhibitors, such as fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (LUVOX), and clomipramine (Anafranil) have been of great interest in autism over the past 10 years because of their effectiveness in treating obsessive-compulsive symptomatology. Repetitive, ritualized, seemingly "compulsive" behavior has been recognized as a major part of autism since its earliest description by Leo Kanner in the 1940s.

Modern diagnostic criteria for autism includes repetitive and stereotyped body movements such as arm-flapping, spinning, and running back and forth (motor stereotypes). Simple rituals such as lining up objects, opening and closing doors, insisting on objects being in a particular place or daily procedures being carried out in a specific way, also form part of modern diagnostic criteria. In addition, more classic "obsessive-compulsive" rituals such as hoarding, washing, counting and touching rituals are frequently seen in autism. These repetitive behavior patterns can be associated with severe anxiety, tantrums and aggressive behavior toward self and others. They may also be highly time-consuming and disruptive to learning.

This group of medications also held interest for autism researchers because of the consistent finding of elevated levels of serotonin in the bloodstream in approximately one-third of individuals with autism. Although this group of medications exerts effects on multiple neurotransmitter systems, these agents are potent blockers of serotonin re-uptake into cells and could potentially reverse some of the serotonin dysregulation in autism.

The three serotonin re-uptake blockers that have been primarily studied in autism are clomipramine (Anafranil), fluvoxamine (LUVOX), and fluoxetine (Prozac). Studies report these agents can reduce the frequency and intensity of repetitive, ritualized behaviors including motor stereotypies and more classic compulsions. In addition, improvements in other autistic symptoms have also been noted. For instance, some children show improvements in eye contact, social initiation and responsiveness. Others show decreased withdrawal and expanded repertoire of interests. Decreased irritability, tantrums and aggression toward self and others have been noted. Improvements in initiating, shifting and sustaining attention are also observed, with improvements in "connectedness" to the environment and therefore less internal preoccupation. Many of these associated benefits may relate to the potent anti-anxiety effects of these medications, although there may also be a direct "alerting" effect related to improvements in certain aspects of joint attention.

These three medications differ in their side effect profiles, with clomipramine (Anafranil) having a greater frequency and severity of adverse effects compared to fluoxetine (Prozac) and fluvoxamine (LUVOX). The most common side effects of all three agents are hyperactive, impulsive behavior and sleep disturbance. Both of these side effects are dose-related and can be minimized with careful and conservative dose titration. Clomipramine (Anafranil) may also cause dry mouth, dizziness and constipation (so-called anti-cholinergic side effects) as well as heart rhythm changes (baseline EKG monitoring is necessary) and a lowering of the seizure threshold (making it a more problematic medication in individuals with seizures). However, in healthy patients without seizures and with normal heart functioning, clomipramine is generally safe and well-tolerated. Each of these three medications have been studied in children and have been found to be safe, with side effect frequency and severity being similar to that seen in adults. Generally, fluoxetine (Prozac) or fluvoxamine (LUVOX) are tried before clomipramine (Anafranil) because of the side effect differences.

A trial of a serotonin reuptake blocker might be considered whenever compulsive behavior, anxiety symptoms, or poor joint attention (severe self-directedness) is significantly impeding developmental, educational, or social progress. A good trial takes 10 to 12 weeks, minimizes the dose, and carefully monitors target symptoms as well as potential side effects.

Other types of antidepressant medications have been studied very little in autism. Tricyclic anti-depressants such as desipramine (Norpramin), imipramine (Tofranil), nortriptyline (Pamelor), amytripty- line (Elavil) as well as buproprion (Wellbutrin), a dopamine reuptake blocker, are sometimes used to treat depression as well as inattention, impulsivity and hyperactivity (attention deficit hyperactivity disorder symptoms-ADHD) in the non-autistic population. They occasionally have a role for treating these symptoms in individuals with autism, but variable clinical response and side effects limit their utility.

Anti-anxiety agents such as buspirone (Buspar) and benzodiazapines (Valium, Klonapin, Ativan and Xanax, for example) have been studied little in autism. They are sometimes useful, particularly as an adjunct to a serotonin reuptake blocker, in the treatment of anxiety. However, behavioral side effects such as disinhibition, crying and irritability limit the use of benzodiazapines.

Stimulant & Other ADHD Medications

Despite the widespread use of stimulant medications for the treatment of inattention, impulsivity and hyperactivity in children diagnosed with ADHD, these agents have been studied very little in individuals with ASD, although clinicians frequently prescribed them. Methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and a dextroamphetamine/amphetamine composite (Adderall) are the most commonly prescribed stimulants. Indeed, they can improve focus, decrease distractibility as well as decrease impulsivity and hyperactivity in autism, but their use is frequently limited by behavioral side effects including increased perseveration, increased repetitive behaviors, and irritability. In my experience, they are better tolerated and more useful in the Asperger' s population. Dosage needs to be carefully titrated because behavioral side effects are often dose-related and can be often avoided if dose is minimized.

A second group of frequently prescribed medications for ADHD are the norepinephrine blockers (alpha-2-agonists) clonidine (Catapress), and guanfacine (Tenex). These agents have less direct effect on focusing than the stimulants but are useful in treating impulsivity and hyperactivity as well as sleep difficulties, which are frequently present in the ADHD population. To date, they have been studied little in the autistic population. In my experience, they can be useful in treating hyperactivity and impulsivity in some autistic individuals with sedation and irritability being the most common side effects. Clonidine is also useful for treating insomnia in autism.

Mood Stabilizers

The most commonly used medications for treating intense, rapid mood shifts are anti-seizure medications such as valproic acid (Depakene or Depakote), carbamazepine (Tegretol), gabapentin (Neurontin) and lamotragine (Lamictal). Lithium is also an effective mood stabilizer. These medications are most commonly used in children and adults with bipolar disorders and other conditions with prominent mood swings. They have been studied very little in terms of their effect on autism, but in my experience are quite helpful for treating severe mood swings, outbursts, and episodic aggressive behavior. Side effects vary from mild to potentially severe depending upon the agent, and blood monitoring is required for many of these agents, which sometimes limits their use. However, overall they are generally well-tolerated and helpful with this group of target symptoms.

Conclusion

We currently have available to us a number of medications which can help improve the quality of life for individuals with autism and their families. Most of these medications address associated behaviors frequently present in autism such as outbursts, aggression, anxiety, inattention, hyper-activity and insomnia. However, "core autistic symptoms" such as repetitive behaviors and "self-directedness" can also be reduced in some cases. There are no medications that directly address cognitive impairments such as language difficulties or deficits in abstract thinking and social understanding, although the medications may enable individuals with autism to better handle educational, behavioral, or other psychosocial interventions that address these deficits.

We are living in an age in which our understanding of brain development and genetics is literally exploding. New psychopharmacologial agents are entering the market each year, and many of these agents can be borrowed by clinicians treating autism. Funding for psychopharmacologial research in autism has dramatically risen, and the number of interested researchers is on the rise. As we gain a better understanding of the basic underlying causes of autism, more specific treatments can be developed. Autism treatment has a very bright future.

C.T. Gordon, III, M.D., is a child psychiatrist in private practice in Bethesda, MD and a founding trustee of the National Alliance for Autism Research (NAAR). He is also the father of a child with autism and currently serves on NAAR's Medical Affairs Committee.
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Author:Gordon, C.T., III
Publication:The Exceptional Parent
Geographic Code:1USA
Date:Jan 1, 2003
Words:1348
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