Wednesday, December 07, 2005

Autism and Drugs

This kind:

...not this kind:
Like many parents, I would rather not use drugs on my child unless absolutely necessary. On the other hand, I believe they might be useful with some children in augmenting behavioral intervention programs, sensory integration techniques, and occupational or physical therapy. Temple Grandin, a high-functioning autistic herself, has some great advice on the use of drugs for the treatment of autism: http://www.autism.org/temple/meds.html

During James’s first visit with the neurologist, back when he was four, we discussed ADHD medication. James’s neurologist mentioned that a lot of his PDD patients that had speech delay also had ADHD characteristics; on the other hand, he thought James was too young, and I also wanted to give James a break and wait. (See the blog on “Dr. Kendal Stewart” for our experience with Valtrex and Strattera.)

Last December, when he was five, James began to exhibit more aggressive behavior. Today James is in a “Functional Life Skills” program, and we are still working on his behavior issues. Although he can academically do most of the work assigned to him, he is impulsive, “testy” or defiant, often refuses to work, needs constant redirection, and hits other children on a regular basis—behaviors that are keeping him out of the mainstream classroom.

Because I was hesitant to jump right into ADHD medications, I went to a nutritional oncologist who recommended nutritional supplements often used for increasing serotonin levels. This did not work so well. I stopped his supplementation after five months.

A few months ago James’s neurologist and I discussed using a norepinephrine antagonist, Catapres (Clonidine), as a safer, milder alterative to ADHD medication; something to take the edge off of his tantrums and aggressive behaviors. After trying Clonidine for a month, we met again and looked at James’s aggressive behavior and obsessive-compulsive tendencies.

The clonidine seemed to help a little bit. We also discussed two other stronger classes of drugs, neuroleptics for aggression and antidepressants for obsessive-compulsive tendencies. For the time being we’ll stick with Catapres because of the lower risk.

I’ll go into a bit more details on these five classes of drugs. Here they are, as grouped by lower-risk, higher risk:

Lower Risk :
Nutrients affecting Methylation, Serotonin Production
Norepinephrine Antagonist

Higher Risk:
Neuroleptics
Serotonin-Selective Re-uptake Inhibitors (SSRI), or “Antidepressants”
Stimulants (ADHD drugs)


Nutrients affecting methylation of Serotonin
TMG (tri-methyl-glycine)
DMG (di-methyl-glycine)
5-HTP (5-hydroxy-tryptophan),
SAMe (S-adenosylmethionine)

Serotonin (5-Hydroxytryptamine, 5-HT) is an important neurotransmitter that affects mood, hunger and sleep. TMG breaks down into DMG and SAMe. TMG, DMG, 5-HTP, and SAMe are nutritional supplements (therefore not regulated by the FDA) commonly used to enhance the methalation of serotonin.

Companies that sell 5-HTP claim that it “passes into the brain immediately” or “easily crosses the blood-brain barrier”, while tryptophan “must compete with other protiens [sic; amino acids] to be transported across the blood-brain barrier.” But there seems to be challenges to this claim (see http://www.ceri.com/rev-sero.htm), which makes me skeptical.

Nevertheless, after meeting with a nutritional oncologist for a couple of hours, I put James on daily regimen of TMG, 5-HTP, and “pharmaceutical grade” lecithin supplements for over five months. (Extremely low risk.) Unfortunately, I observed no significant changes. When I discussed this with our neurologist, his opinion was that 5-HTP and tryptophan simply does not work because increasing serotonin levels isn’t enough for many people. Instead, establishing the correct ratio of serotonin at the brain synapses is what is important.

Although I’m sure many people have benefited from 5-HTP, DMG, TMG, and SAMe (I’ve talked to some that swear by it), James does not seem to fall into this category.


TMG, DMG
http://www.autism.org/dmg.html

5-HTP
http://www.vanderbilt.edu/AnS/psychology/health_psychology/5htp_myth.htm

SAMe
http://www.biopsychiatry.com/sameart.html

Tryptophan, 5-HTP and Serotonin
http://www.ceri.com/rev-sero.htm

James does take two types of liquid vitamins which certainly don't hurt:
Liquid Health™ Children's Multiple and
Liquid Health™ Children's Attention



Serotonin-Selective Re-uptake Inhibitors (SSRI), or “Antidepressants”
In contrast to 5-HTP and SAMe, which work by increasing the overall amount of serotonin in the body, Serotonin-Selective Re-uptake Inhibitors (SSRI), or “antidepressants,” such as Prozac and Zoloft, work by changing serotonin ratios within the brain. Only one or two percent of the serotonin in the body is in the brain, and that amount is independently synthesized from tryptophan transported across the blood-brain barrier. SSRIs raise serotonin levels within the brain by inhibiting the reuptake (recycling) of serotonin.

SSRIs are commonly prescribed as a treatment for Obsessive/Compulsive Disorder (OCD). Many PDD and autistic children exhibit obsessive-compulsive behaviors, such as impulsiveness, repetitive preoccupations, and perseveration. James’s speech and physical/occupational therapists have noted that his obsessive/compulsive tendencies are strong, even when compared to other autistic and ADHD children they have encountered in their practice.

Unfortunately, the side effects associated with Prozac and Zoloft can be rather severe. Because of James’s age and other factors, I’m not going to try SSRIs at this point but have not ruled them out for future evaluation.

Neurotransmitter Primer
http://www.benbest.com/science/anatmind/anatmd10.html

Autism and SSRIs
http://www.childadvocate.net/autism_and_SSRI.htm



Stimulants
According to James’s neurologist, a lot of kids that are autistic/PDD with speech delay tend to exhibit ADHD characteristics. Many of these children are on ADHD drugs (stimulants) such as Ritalin and Adderall.

Although ADHD children are hyperactive, stimulants at the dosages used for ADHD can appear to calm many hyperactive children. Although how stimulants exactly do this still isn’t exactly known, many studies and a lot of research indicates that stimulants work primarily by increasing dopamine levels in the brain. Dopamine helps regulate inhibitions but also promotes feelings of well-being and satisfaction. Stimulants also enhance levels of the neurotransmitters serotonin and noradrenaline (norepinepherine), which can help regulate impulsiveness. Stimulants have been also shown to increase the blood flow in the brain and neural activity in the frontal lobes.

I have known several children and adults who have taken these drugs, and their experience varies. For example, James’s uncle said it would always have him feeling “sick” or “not right,” so he would spit the pills out; on the other hand, my nine-year-old neighbor is doing great on it. Some of these variances may be due to quality of dosing and appropriate “matching” of the drug to the individual: you’ve got to remember, except for Strattera, most ADHD drugs are stimulants. Cocaine and methamphetamines are stimulants and share some of the same pharmacological effects as ADHD medication; then again, so does caffeine.

I’ve also noticed that some of the people who complain about ADHD drugs the most are parents or kids who felt coerced somehow by school districts. Schools can no longer do this. ADHD medication isn't for everyone and should always be used in conjunction with therapy, not as a substitute for it. I haven’t had this type of experience with the school so far; they’ve been helpful in providing me with observational data and seem to respect the parents’ choices. James’s neurologist did warn me that ADHD drugs are often hit-or-miss, and it may take a few tries to find one that works at the proper dosage. We still don’t know if ADHD medication would help James or not.

Even some ADHD kids don’t respond well to any ADHD stimulant; those kids may have to try the family of tricyclic antidepressants (TCA’s) instead. (Antidepressants will be discussed later in this posting—specifically, the family of atypical antidepressants.) Another alternative to stimulants is Strattera (atomoxetine): unlike stimulants, which works primarily by increasing dopamine levels, Strattera works by increases norepinephrine levels in the brain. While under the care of Dr. Kendal Stewart, James tried Strattera for two weeks because of a study linking Strattera with improved speech. It had no effect. When I mentioned this to my neurologist, he urged me to stop for three reasons: James was only four at the time, the study wasn’t compelling enough, and Strattera was very new. Several months later the liver damage lawsuits came to light, so we won’t be trying Strattera again.

The last thing I want to do is turn James into a zombie or stress his body out at a young age. I have mixed feelings about going down the ADHD drug route, and many people have strong feelings both ways. I do not believe it is necessary for us at this time, but I have not ruled it out for future use. As James matures and progresses in school I’ll keep re-evaluating, and do a bit more research in this area. The day may come when we will have to try ADHD medication, but only for the right reasons.

http://www.pbs.org/wgbh/pages/frontline/shows/medicating/drugs/
http://www.pbs.org/wgbh/pages/frontline/shows/medicating/adhd/
http://www.pbs.org/wgbh/pages/frontline/shows/medicating/backlash/
http://kidshealth.org/parent/emotions/behavior/adhd.html
http://www.kidsmentalhealth.org/Stimulants.html
http://www.wildestcolts.com/mentalhealth/stimulants.html
http://www.ablechild.org/
http://groups.msn.com/psychbusters/addadhd.msnw



Neuroleptics
Atypical Neuroleptics (a.k.a. Atypical Antipsychotics) target dopamine and serotonin receptors, which control behavioral problems such as self-injury, aggression, hyperactivity, and tantrums. Common side effects include weight gain. Rare but serious side effects include neuroleptic malignant syndrome (very rare but serious neuro-muscular rigidity symptoms, sometimes life-threatening) and tardive dyskinesia (motor dysfunctions, such as tongue movements, facial tics).

Of the following Atypical Neuroelptics:
Risperdal (risperidone),
Seroquel (quetiapine),
Zyprexa (olanzapine),
Zeldox (ziprasidone), and
Clozaril (clozapine),

James’s neurologist recommended that if we were to try a neuroleptic, consider Seroquel because of reduced side effects. James does exhibit some aggressive behavior at school, but a lot of it can still be controlled simply through redirection and discipline. The milder Clonidine (a norepinephrine antagonist, not a neuroleptic) that James is taking seems to be helping, so I’m going to wait before going to something stronger—again, the side-effects are a big concern for me. I’m also still trying to figure out if his aggression is more related to his obsessive-compulsive traits, environment, or other social factors.

Antipscyhotics/Neuroleptics,
SRIs (Selective Seratonin Reuptake Inhibitors)/Antidepressants,
And Stimulant Use in Autism:
http://www.autismlink.com/info/autism_medications.php

Seroquel (quetiapine):
http://www.seroquel.com/



Norepinephrine Antagonist
Since norepinephrine agonists such as amphetamines or methylphenidate have been shown to worsen autistic behaviors, one rationale for using a norepinephrine antagonist such as Catapres (clonidine hydrochloride USP) is that it could reduce autistic behaviors. Several double-blinded placebo-controlled studies in the 1990s appear to confirm this.

Catapres (clonidine) is commonly used for reducing hypertension and is an extremely safe drug, easy on the liver and kidneys. Clonidine basically has a mild calming effect, and has been demonstrated to be effective also as a sleeping agent (mild sedative). The effects are short (four to five hours), so it is typically dosed early in the morning and at noon.

Although clonidine is not as strong as stimulants (ADHD medication), neuroleptics (antipsychotics), or antidepressants, the negative side effects are generally mild and low risk. (They are “easy on the organs.”) It has to be taken at reduced dosages for a couple of weeks at the beginning and end of treatment; otherwise, blood pressure will drop at the beginning or rise when abruptly stopped. It also has to be taken regularly for similar reasons. Blood pressure and heart rate should be monitored regularly, especially during the two weeks or so it takes to come on and off the drug. Other than low blood pressure, the main side effects are fatigue and sleepiness. Since the body can get used to it, its effectiveness may be reduced over time.

James has been on clonidine for over a month now (started on October 30th). Although it hasn’t given anyone a “Wow!” effect, I’ve seen a few mild positive changes: he sleeps longer at night, and goes to bed earlier; he is a little bit easier to redirect; his tantrums are shorter, milder. The change is subtle but noticeable also by his teachers, therapists, and myself. Although feedback from his therapists has been positive, his teacher at school (where he spends the most time) did say that although the intensity of his behaviors has decreased slightly, and his tantrums are milder, he is misbehaving more often. He is also coming up with progressively worse negative behaviors, such as throwing objects at the window (used to throw at wall), picking up computers (rather than just pushing them).

Oh well, medication isn’t going to solve everything.

For now, I’m going to stick with it a little longer. Even a 10% improvement is worth it, since the risks with this drug are low. Also I’ve noticed that around this time of the year—when it gets darker and the temperature drops—he can work himself into these giddy, manic fits where he won’t stay still, can’t be held still, gets into everything, and won’t make eye contact even if you’re right up in his face. It’s similar to but not quite a “glazed” look. His speech therapist summed it up rather well: “it’s as if he isn’t with us today.” Two weeks or so before we started clonidine he had a few episodes like this, and I thought, “Oh no, not again.” But this hasn’t happened since. I’m not sure if it is the clonidine, or if it’s just on his own. I’ll probably stick with it at least a few more months, until it gets warmer, with longer days (early Spring). Last Winter was especially bad.

http://www.psyweb.com/Drughtm/jsp/clonid.jsp
http://www.vh.org/adult/provider/psychiatry/CPS/41.html
http://www.pslgroup.com/dg/221262.htm
http://www.remedyfind.com/rem.asp?ID=5435
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1548248&dopt=Abstract

http://www.rxlist.com/cgi/generic/clonidin.htm
http://www.rxlist.com/cgi/generic/clonidin_cp.htm
http://www.rxlist.com/cgi/generic/clonidin_ids.htm
http://www.rxlist.com/cgi/generic/clonidin_ad.htm
http://www.rxlist.com/cgi/generic/clonidin_wcp.htm
http://www.rxlist.com/cgi/generic/clonidin_od.htm
http://www.rxlist.com/cgi/generic/clonidin_pi.htm



Other Links:

Overview of antidepressants, anti-anxiety drugs, antispasmodic medications, stimulants, neuroleptics, and other medications used in the treatment of PDD:
http://www.patientcenters.com/autism/news/meds.html

Overview of clinical trails for drugs used in the treatment of autism:
http://www.vh.org/adult/provider/psychiatry/CPS/41.html

Temple Grandin on Prozac and Zoloft (SRIs/Antidepressants) and drugs in general:
http://www.autism.org/temple/meds.html

Specific drug mongraphs
http://www.healing-arts.org/children/ADHD/medications.htm
http://www.rxlist.com/



DISCLAIMER: I am a NOT a physician and do not work in any medical profession. I’m just a parent; a layman. You should talk to as many qualified doctors as you can about drug options and decide based on your own child’s needs.