|
|
|
Treatment research of autism disorder is lacking. Some of the few research appears industry-funded studies of newer medications with higher profit margins. All studies are small. Many of the reports are unethical promotional "open-trial" reports, which have no scientific validity, e.g. the expensive and patented Ramelteon in two children, the very expensive patented Alzheimer's medicines: galantamine (J Child Adoles Psychopharm 2006 Oct;16(5):631-6) and Namenda (Psychopharmacol (Berl) 2006 Oct 3), and Strattera, a very expensive patented ADHD medication (J Child Adoles Psychopharm 2006 Oct;16(5):599-610). SSRI anti-depressants and atypical anti-psychotics such as risperidone are most often used. Very few studies exist for Asperger's syndrome, even though it may be an altogether different group of disorders from autism. I urge all autistic patients be given a multivitamin with minerals daily and an extra 400 mcg of folic acid, an adequate source of omega-3 fatty acids (e.g. 2-5 fish or flax oil capsules per day), and melatonin (6-12 mg/night). If an anti-psychotic is used, I prefer to try Geodon, perphenazine, or Abilify in order to avoid weight gain. Treat ADHD or depressive symptoms only if present in significant quantity. Amantidine, vitamin C and carnosine have favorable studies. ADHD: Pervasive Developmental Disorder ADHD Helped Less with More Side-Effects: In a DB PC crossover study of 66 drug-free children, ages 5 to 14, with pervasive developmental disorders accompanied by moderate to severe hyperactivity, methylphenidate from 7.5 mg/d to 50.0 mg/d was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54. 49% were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 18%. The magnitude of response was less than that seen in typically developing children with ADHD. Adverse effects were more frequent. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Research Units on Pediatric Psychopharmacology Autism Network. Arch Gen Psychiatry 2005 Nov;62(11):1266-74. Amantidine Helped Some in Short Study: In a 3-week DB PC study of 39 autistic children of amantadine (5.0 mg/kg per day), the mean parent-rated placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in clinician-rated hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. King BH, Wright DM, et al. Dartmouth. J Am Acad Child Adolesc Psychiatry. 2001 Jun;40(6):658-65 Atomoxetine Helped ADHD Symptoms in Small DB: In a DB PC crossover 6-week each phase study of 16 autism spectrum disorder children ages 5-15 with ADHD symptoms using the Hyperactivity subscale of the Aberrant Behavior Checklist, ATX was superior to placebo (p =.043, effect size d = 0.90). It was also superior on a 0 to 3 rating of nine DSM-IV ADHD hyperactive/impulsive symptoms (p =.005, d = 1.27), but missed significance on nine inattentive symptoms (p =.053, d= 0.89). Nine subjects responded while on ATX, four on placebo (25% improvement). One was rehospitalized for recurrent violence on ATX. Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial. Arnold LE, et al. Ohio State University. . J Am Acad Child Adoles Psychiatry 2006 Oct;45(10):1196-205. Buspirone (Buspar) Said to Help: In a very poor quality report, authors claim that anxiety in 22 children with PDD in an open study who received 15-45 mg/d of buspirone for 6-8 weeks found nine doing much better, and 7 moderately better. Jan Buitelaar, Utrecht, ’98 59:56-9. Ed: Buspar has been a disappointing anti-anxiety agent with many DB studies showing benefit compared to placebo, but other studies, not funded by the manufacturer, finding it inferior to a number of other medications. Carnosine Helped Autistic: A DB PC 8-week study of 31 autistic children half given l-carnosine 800 mg/day found statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. Chez MG, Buchanan CP, et al. J Child Neurol. 2002 Nov;17(11):833-7. These capsules are available for about $20 a month from health food sources. Fluoxetine (Prozac) Claimed to Help Those with Family History of Depression, Hyperlexia: Of children in what was apparently an uncontrolled trial, 22 (17%) did very well while on fluoxetine, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with improvement. Fluoxetine "response" was supposedly "robustly" correlated with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Authors say fluoxetine "response," family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Duke. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. DeLong GR, Ritch CR, Burch S. Dev Med Child Neurol 2002 Oct;44(10):652-9. Ed: This appears to be another very poor quality "open-label" report from Duke. Only with double-blind research is it appropriate to talk of a response. Open trials should not even be published in my open, in view of the disastrous harm they have caused thousands of patients when physicians jump to the conclusion that the open trial proved something and start using the medication on patients. Fluvoxamine (Luvox) Helped in DB: 30 18-53yos DB PC 12 weeks up to fluvoxamine 300/d. CGI high for fluvoxamine by week 4. Eight of 15 on fluvoxamine vs. 0 of 15 placebo were rated much or very much improved. They had reductions in repetitive thoughts and behavior, maladaptive behavior, and aggression, improved language use, less echolalia, better communication. McDougle C, et al: A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psyc 96;53:1001-8, Yale. Haldol better than Clomipramine: 36 DB PC 7 week. Haldol 1-1.5mg/d vs clomipramine 100-150. Equal efficacy with completers but much higher clomipramine dropout with side-effects or lack of efficacy. Intent to rx 70% vs 38%. Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study. Remington G, Sloman L, et al. J Clin Psychopharmacol 2001 Aug;21(4):440-4. Levetiracetam No Benefit: The anticonvulsant levetiracetam in the treatment of children with autism did no better than placebo in a 10-week DB PC study of 20 children ages 5-17 with autism. A previous open-label study in autistic children treated with levetiracetam claimed to have demonstrated effectiveness in hyperactivity, impulsivity/aggression, and mood lability. Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study. Wasserman S, et al. Mount Sinai School of Medicine, New York, NY. . Int Clin Psychopharm 2006 Nov;21(6):363-7. Ed: This study is good evidence as to why it is unethical to publish open-trial reports which have caused hundreds of thousands of patients to be exposed to bogus treatments. Naltrexone Only Suggestion of Benefit in DB: After a 2-week placebo baseline period, 41 autistic children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Naltrexone in autistic children: behavioral symptoms and attentional learning. Campbell M, et al. New York University Medical Center. J Am Acad Child Adolesc Psychiatry. 1993 Nov;32(6):1283-91. Naltrexone (Revia) Didn't Help Autism or Self-Injurious: In a DB PC crossover study of 33 mentally retarded adults with autism and/or self-injurious behavior, active treatment was first a single 100-mg dose of naltrexone hydrochloride. Subsequently, 19 subjects were treated with 50 mg/d and 14 with 150 mg/d of naltrexone hydrochloride for 4 weeks. Naltrexone treatment failed to have therapeutic effects on SIB and autism. On the contrary, naltrexone increased the incidence of stereotypic behavior on the Aberrant Behavior Checklist, and the care staff evaluated the effect of the 50-mg/d treatment as being significantly worse than that of the placebo treatment. Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies. Willemsen-Swinkels SH, et al. University of Utrecht, The Netherlands. Arch Gen Psychiatry. 1995 Sep;52(9):766-73. N,N-dimethylglycine No Benefit: N,N-dimethylglycine, a dietary supplement, has been reported to be beneficial in children with autism and pervasive developmental disorder but not in a previous double-blind study. However, in a 4-week, DB PC study of 37 children ages 3-11 with autism and pervasive developmental disorder, standardized neurologic examinations before and after treatment on 33 children showed no change. An overall improvement on all behavioral measures was observed for both the placebo and the dimethylglycine groups. However, the improvement among the children who received dimethylglycine was not statistically different from the improvement observed among the children who received the placebo. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. Kern JK, et al. University of Texas at Dallas. . J Child Neurol 2001 Mar;16(3):169-73. N,N-dimethylglycine No Benefit in Very Small Study: Although the very influential nonmedical literature cited in the Autism Research Review International Newsletter finds that dimethylglycine (DMG) is regarded as more effective than the usual psychopharmacologic drugs, there have been no studies of DMG using the currently accepted research methodology. In the DB PC i-month crossover pilot study of low dose DMG and placebo of eight autistic males ages 4-30, who completed the full 3 1/2-month study consisting of drug-free baseline periods at the beginning, end, and in-between two, 1-month double-blind trials in which DMG or placebo was given, analysis of three different scales revealed no statistically significant differences, and parent reports were equally distributed. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. Bolman WM, et al. J Autism Dev Disorder 1999 Jun;29(3):191-4. Omega-3 Fatty Acids Tended to Help in Very Small DB: In a DB PC study for 6-weeks with 13 children (ages 5-17) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior, there was an advantage of 1.5 g/day (equal to 5 1 g fish oil capsules/day) of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Amminger GP, et al. University of Melbourne, Australia. Biol Psychiatry 2006 Aug 22. Ed: This was an extremely small study. Flax seed or flour might be easier to get children to take or purchasing special, smaller concentrate omega-3 fish oil capsules, since fish oil capsules are usually too large for children. Omega-3/Omega-6 Help Learning and Behavior: Developmental co-ordination disorder (DCD) affects 5% of school-aged children and is associated with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. A relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. In a 3-month DB PC crossover study of 117 children with DCD ages 5-12, no effect of the omega-3/omega-6 supplement on motor skills was apparent, but significant improvements were found in reading, spelling, and behavior. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress. The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental co-ordination disorder. Richardson A. J., Montgomery P. (2005) Pediatrics, 115, 1360-1366. Porcine Secretin No Benefit: DB PC 64 2-7yos with DSM-IV autism. 2 injections 6 weeks apart. Language, cognition, social and behavioral assessed. No differences. Roberts W et al: Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial. Pediatrics 01;107:e71, Univ. Toronto Pyridoxine and Magnesium No Benefit: A 12-patient DB PC study for 10 weeks of high dose pyridoxine averaging 640 mg/day and magnesium averaging 216 mg/day found no benefit. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. Findling RL, Maxwell K, et al. J Autism Dev Disord. 1997 Aug;27(4):467-78 Atypical Anti-Psychotic Helped Repetitive Autistic Behaviors But Not Communications: Risperidone has been found helpful for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). In a study analyzing the results from a DB PC trial of 101 autistic children and 16-week open-label continuation study of 63, risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. McDougle CJ, Scahill L, et al. Indiana University. Am J Psychiatry. 2005 Jun;162(6):1142-8. Risperidone Claimed Helpful: The manufacturer did a subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. In 55 children given risperidone (n = 27) or placebo (n = 28), risperidone [mean dose 1.37 mg/day] resulted in greater reduction vs. placebo [mean change -13.4 vs. -7.2, P < 0.05]. The most common adverse effect with risperidone was somnolence (74% vs. 7% with placebo). Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial. Pandina GJ, et al. Janssen Pharmaceutica. J Autism Dev Disorder 2006 Oct 4. Ed: This dubious report appears to be a post-hoc analysis of the data by the manufacturer. Risperidone Helps But at Cost of Weight Gain: Only 3 randomised controlled trials were found in a comprehensive search. Some evidence of the benefits of risperidone in irritability, repetition and social withdrawal were apparent. These must however be considered against the adverse effects, the most prominent being weight gain. Risperidone for autism spectrum disorder. Jesner O, et al. Risperidone Helped in DB: In a 6-month DB PC study of 40 children with autism, ages 2-9, risperidone in 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism. Risperidone in children with autism: randomized, placebo-controlled, double-blind study. Nagaraj R, et al. Chandigarh, India. J Child Neurol 2006 Jun;21(6):450-5. Risperidone Helped Autism and Pervasive Developmental Disorders: In an 8-week DB PC study of 79 children ages 5-12 with autism and other pervasive developmental disorders (PDD), risperidone (0.01-0.06 mg/kg/day) led to a significant decrease in irritability (64% vs. 31% for placebo). Significantly greater decreases were also found on conduct problems, insecure/anxious, hyperactive and overly sensitive test subscales. More risperidone-treated subjects showed global improvement (87% vs. 40%). Somnolence was noted in 72% vs. 8% of children. Risperidone led to more weight gain (6 pounds vs. 2 pounds), pulse rate and systolic blood pressure. Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disorders. Shea S, Turgay A, et al. (2004) Pediatrics, 114, e634-e641. Ed: If using an atypical anti-psychotic, ziprasidone (Geodon) might be a better first choice in view of its lack of weight gain and much lower cost. Risperidone Helps in DB; Maybe Fluvoxamine and Clomipramine: 31 adults with autistic or Pervasive Developmental Disorder were treated for 12 weeks in a DB PC study. There were 57% responders at average dose of 3 mg. risperidone. There was decreased repetitive behavior, aggression, anxiety, nervousness, depression, irritability, and overall functioning. No change social or language. Chris McDougle, Indiana Univ, Arch Gen Psychiatry 7/98 55:633-41. One prospective long study found 34% autistic kids had dyskinesia from haloperidol. Fluvoxamine for adults did better than placebo. Clomipramine for kids did better than desipramine or placebo. Risperidone Helps in DB: 101 children treated by Yale in a DB PC study found 69% improved considerably while on risperidone vs. 12% with placebo. NEJM 8/2/02 Vitamin C Might Help: In a 10-week/phase double-blind, placebo-controlled crossover trial of 18 children with autism, ascorbic acid (8g/70kg/day), there was a reduction for total scores and also abnormal sensory motor scores associated with the ascorbic acid treatment. A preliminary trial of ascorbic acid as supplemental therapy for autism. Dolske, MC, et al. University of Alabama at Birmingham. Prog Neuropsychopharm Biol Psychiatry 1993 Sep;17(5):765-74. Ziprasidone (Geodon) Helped in Poor Quality Open Trial: In a very poor quality report, 6 of 12 children given ziprasidone were at least much improved while on ziprasidone. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. McDougle CJ, Kem DL, Posey DJ. J Am Acad Child Adolesc Psychiatry 2002 Aug;41(8):921-7 (Ed: Open trials are of little value due to the dangers of observer bias. I do like ziprasidone, since it doesn't cause the weight gain of risperidone.) Thomas E. Radecki, M.D., J.D. |