FIRST things first: Children, Drugs, and Over-Medication
Before we begin, I must say that regardless of whether or not Risperdal can help alleviate the symptoms of autism--or perhaps just effectively tranquilize the children--the point still remains that drugs (particularly anti-psychotics) are powerful and possibly harmful to young children; and Americans love over-medicating themselves and their children. According to [adrugrecall.com], "Children Advocates find the over prescribing of drugs like Risperdal to children is a form of drug abuse in children that has become a national epidemic." Children are DYING needlessly from side-effects of drugs they should not be taking in the first place. Drugs have become the lazy, quick-fix option for every problem, to the point where "only one in 10 children who visit a child psychiatrist's office leaves without a psychiatric drug prescription" [A Prescription for Disaster // www.salon.com].
Even when a child might actually NEED an anti-psychotic, its use can still be dangerous. In an article [The Last Word: Pediatric Drug Research and Mental Illness // www.fda.gov], Floyd R. Sallee, MD and PhD, states that "While the atypical neuroletpics are intended for treating schizophrenia, pediatric practitioners and child psychiatrists are using these agents for early forms of disorders that have not yet reached full expression. These mental health professionals rarely see children who meet full criteria for schizophrenia." Schizophrenia usually does not appear until young adult-hood, so it's really difficult to diagnose it (or bipolar mania) in such young children. Even if the child does have the disease, "Children may indeed be at greatest risk from the atypical neuroleptic drug class, not just because of a rapidly developing brain, but also potential sensitivities to certain cardiac arrythmias and the well-documented weight gain assosicated with this drug class." Pumping a child full of drugs while that child's brain is still growing can cause damage that will last a life-time, and possibly cause more problems than it temporarily solves.
Finally, even admitting that some drugs might be safe and effective for children who might need them... their use is highly risky and experimental. Only two of the newer psychotropic drugs (Paxil and Luvox) have been sufficiently tested and FDA approved for children (for OCD) [salon.com]. The rest are prescribed off-label under the faulty assumption that children are mini-adults, despite research proving that "adult drug studies do not necessarily correspond to effects in children" [salon.com]. Even when kids are tested, the studies are notorious for inaccuracy. Evaluation criteria are often incredibly vague and subjective, for example. Much is made of single case studies, parent comments, and hear-say. Sadly, few studies fork out the cash to run the best test possible - a double-blind randomized control study (DBRCS), in which "neither the family nor doctor knows whether the child is getting the medication or [the placebo]" [salon.com]. This eliminates doctors and parents "seeing" results that are not really there just because they want to see them, and most accurately reflects REAL efficacy and side effects. Yet even when DBRCS's are done, it is often with the minimum possible number of the kids. In short, pediatric clinical trials have much room for improvement.
With that in mind, here is some info about the few-and-far-between clinical pediatric trials of Risperdal.
THE CLINICAL TRIALS
Risperdal's label states that it has not been established as safe for children under eighteen. I scoured the web and found evidence of five clinical trials involving children. Three of the trials were hardly credible (among other things, they only involved around 10-20 children) and all but one were to test the efficacy of Risperdal in treating random behaviorial problems, or autism, but never schizophrenia or bipolar mania, the mental diseases it is approved for treating. (One study actually investigated the tolerability of Risperdal in children, which is a good thing.) I do not have a lot of info about these trials, and it was hard enough to find what little I did. Sources are provided.
For comparison purposes (since it is sometimes interesting how insignificantly little or how disturbingly much of the drug is given to the children in these trails, or how dangerously quickly the children's dosages are increased), you can find at the bottom of this page the label info about proper dosing. I may refer to it while critiquing the trials.
1988 Study
Published: Journal of Child and Adolescent Psychopharmacology 1988;8(1):49-59 Schreier HASubjects: 11 children and adolescents, aged 5-16, mean age of 9.8 years. The children "had mood disorder symptoms, aggressive and violent behavior, and marked management problems."
Doses: Low (0.75-2.5 mg daily)
Results: "8/11 children responded within 8 days. The improvement was judged to be moderate to marked in 7 of those 8." Side effects included weight gain and mild sedation.
Additional info: 7/8 who responded were taking either lithium, Tegretol, or Depakote in low doses. Performed at the Dept. of Psychiatry at Children's Hospital in Oakland, California
Online Source: [biologicalunhappiness.com/AskDoc...]
My Comments: Why are the children taking other medications at the same time? Of what value is this study when 7/8 children who respond positively were also taking other medications at probably similiar dosage levels? Yet, a second source [biologicalunhappiness.com/RisprKid.htm] seemed to further downplay this statistic, merely stating that "The use of Risperdal alone or with mood stabilizers ... showed significant improvement." Furthermore, I wouldn't be surprised if the 1 child who responded but did not respond positively enough for the improvement to be considered "moderate to marked" was not also the only 1 out of the 8 responders who was not on other drugs. Since the Risperdal dosage was low too, I do not see how this study actually tests Risperdal. Other things I noticed were the extremely low # of subjects, the fact that even at such a low dosage Risperdal still sedated the children and caused weight gain, and that this study was not designed to test ANY mental condition in particular, instead testingchildren with a random hodge-podge of mood/behavioral problems. The children were never even said to have actual mood disorders, only "mood disorder symptoms."
1996 Study
Published: Journal of American Child Adolescent Psychiatry 1996 Nov (Hardan A, Johnson K, Johnson C)Subjects: 20 children, aged 8-17 "with developmental problems unresponsive to previous treatments."
Doses: ranged from 1.2-10.0mg daily.
Results: "8-15 month follow up showed 13/20 were doing well. Most had no side effects, three had marked weight gain, and breast milk formation developed in two adolescent girls."
Online Source: [biologicalunhappiness.com/Risprkid.htm]
My Comments: What does "doing well" mean? Seems vague, with no quantified results. Percentages make things clearer: Only 65% (13/20) supposedly improved. 15% (3/20) gained weight, and 10% (2/20) developed breast milk. Assuming half were girls, then 20% of preadolescent girls developed breast milk, which is kind of disturbing. Even more alarming is the dosage levels. Children were being given up to 10mg daily even though, according to the label, "The safety of doses above 16 mg/day has not been evaluated." Everything on the label refers to dosages for an adult, not a child, and it can be assumed that children should take less. Keeping that in mind... for QD (daily) dosing, all the label says is that studies have proven that 8mg/day is more effective than 4mg/day. For BID (bidaily) dosing, the label says "Doses above 6 mg/day for BID dosing were not demonstrated to be more efficacious then lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are not generally recommended." I'm glad the children got out of this study alive.
2000 Study
Published: unsure; presented at the 49th Annual Mtg. of the American Academy of Child and Adolescent PsychiatrySubjects: 79 children, ages 5-12, with PDD (pervasive developmental disorders) - 56 had autistic disorder, 1 had childhood disintegrative disorder, 12 had Asberger's disorder, and 11 had PDD "not otherwise specified".
Doses: ranged from .01 - .06 mg/day, with average of .04 mg/kg/day
Additional Info: Investigators assessed the children's behavioural sumptoms with the ABC (Abberant Behavioural Checklist, the N-CBRF (Nisonger Child Behaviour Rating form), and the CGI (Clinical Global Impression scale. "They assessed medication safety by vital signs, electrocardiogram, documentation of extrapyramidal symptoms (EPS), incidence of adverse events, and laboratory tests."
Results: Dr. Sarah E. Shea claimed that "we found risperidone to be significantly helpful for addressing a variety of difficult behavioral sumptoms assosicated with PDD ... Key among these were behaviors associated with irritability, such as self-abuse, tantrums, and aggression." The children taking risperidone had "a significant decrease on the ABC irritability subscale (p<0.001) as well as other ABC subscales (p<0.05) and the N-CBRF Conduct Problem subscale (p<0.01), in contrast to those in the placebo [group]. The treatment group also had an 85 percent increase in the CGI, while the placebo group's CGI improved a mean of 42 percent."
Side effects: included a 72.5% rate of somnolence, compared to only 10.3% of placebo subjects. More than 20% in the treatment group also experienced "upper respiratory infection, rhinitis, increased appetite, abdominal pain, and weight gain." Ten developed extrapyramidal symptoms, compared to four in the placebo group.
Online Source: [pslgroup.com]
My Comments: At least this was a REAL experiment. The dosage levels were safe (I particularly liked how they listed the average dosage as an amount of mg per kg of each child's body) and, unlike the other experiments, it had actual, specific guidelines for evaluating the children's progress. However, though I like that the dosages were low (making them safe) I wonder how .01mg of a drug that patients (adults) usually take about 4-8 mg a day of can have much of any effect on a disease. I'm concerned by the high rate of somnolence despite these VERY low dosage levels. Also, I do not understand the rating subscales. What does something like (p<0.001) mean, and is that not a very low small improvement? This study seemed very professional though.
2002 Study
Published: "New England Journal of Medicine," August 1, 2002; conducted by the NIMH (National Institute of Mental Health)Subjects: 101 (82 boys, 19 girls) autistic children, aged 5-17 years.
Doses: unsure
Additional Info: Eight week trial.
Results: 69% of the Risperdal children showed "much to very much improvement in aggressive behavior as opposed to only 12% of the placebo group. Investigators analyzing the data say this is the single most effective medication study in regards to the treatment of autism." Side effects included rapid weight gain in some of the children, averaging about six pounds over the eight week trial.
Online Source: [autism.about.com]
My Comments: What does "much to very much improvement" mean? It does not seem the scientists observed the children very carefully, or using any specific criteria, especially when we consider how little side effects were reported. Considering the results of all the other studies - with only 10 or 20 children - I find it hard to believe that the only side effect was weight gain. Consider the carefully done 2000 study (above), which admitted a 72.5% rate of somnolence. Yet here, we are to believe the rate is zero? I would like more info on this study. I am also bothered by the fact that there were only 19 out of 101 subjects were female.
another 2002 Study
Published: unsure; pilot study presented at the American Psychiatric Association, 2002 Annual Mtg.Subjects: 10 hospitalized children, aged 7-10 years.
Doses: administered "gradually to 0.04 mg/kg/day as clinically indicated and only if tolerated"
Additional Info: (1) Notice that no mental disorders or improvements in the children's condition were mentioned (though I would assume they would not just give the drug to healthy children). This is because the study was designed specifically "to determine the tolerability of Risperidone in children". (2) Ten day average study period.
Results/Side Effects: Three (30%) developed "mild degree of loss of appetite," and one of those three also had diarrhea. One (10%) developed mild rigidity, drooling, and slurred speech, and one (10%) had mild sedation. Three gained weight, and one lost weight. This was evaluated as an "unexpected high rate of side effects," and the article suggests that more (and long-term) studies are needed.
Online Source: [childadvocate.net]
My Comments: I commend the study for investigating the SAFETY of Risperdal in children. It is important to determine risk factors before seeing how well a drug cures random diseases. (What good is a "cure" if it kills the patient?) It seemed concerned about the children's safety, mentioned the average doses as mg per kg of the child's weight, and followed safe and proper dosing techniques. However, it only tested 10 children for 10 days, which does not make this experiment very significant. As for evaluating the drug itself... the "unexpected high rate of side effects" in such a small group of children taking healthy dosages speaks for itself.
Label Excerpt on DOSING:
RISPERDAL ... can be administered either on a BID [bi-daily] or a QD [daily] schedule. In early clinical trials, RISPERDAL was generally administered at 1 mg BID initially, with increases in increments of 1 mg BID on the second and third day, as tolerated, to a target dose of 3 mg BID by the third day. Subsequent controlled trials have indicated that total daily risperidone doses of up to 8 mg on a QD schedule are also safe and effective ... Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week ... When dosage adjustments are necessary, small dose increments of 1-2 mg are recommended. Efficacy in schizophrenia was demonstrated in a dose range of 4 to 16 mg/day ... however, the maximal effect was generally seen in a range of 4 to 8 mg/day. Doses above 6 mg/day for BID dosing were not demonstrated to be more efficacious then lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are not generally recommended. In a single study supporting QD dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg/day has not been evaluated in clinical trials. [Risperdal label // fda.gov]
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