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Ritalin Associated Heart Deaths: In the U.S. since 1999, 51 children and adults with ADHD have died while on methylphenidate. Another 9 have died in the United Kingdom. The FDA is finally requiring a black box warning. Adderall was briefly banned in Canada in 2005 for the same reason. http://www.guardian.co.uk/frontpage/story/0,,1707535,00.html Stimulants Cause Hallucinations: An FDA panel recommended parents and doctors be warned that stimulants many cause hallucinations including visual ones of worms, snakes, or insects and this may occur in up to 5%. New Scientist 4/1/06. Bipolar disorder may also be caused by such treatments and may account for why bipolar disorder is so high in American children, compared to those of other developed countries. 28% of ADHD Children Became Bipolar: In a 6-year, prospective study of only 81 ADHD children ages 6-12, the rate of switching from attention-deficit/hyperactivity disorder (ADHD) to a prepubertal and early adolescent bipolar I disorder phenotype (PEA-BP-I) was 28.5%. Significant predictors of switching were more severe baseline CGAS, paternal recurrent MDD, and less stimulant use. BP I in first-degree relatives, antidepressants, psychosocial measures, and life events were not predictive. Controlled study of switching from attention-deficit/hyperactivity disorder to a prepubertal and early adolescent bipolar I disorder phenotype during 6-year prospective follow-up: Rate, risk, and predictors. Tillman R, et al. Washington University, St. Louis. Developmental Psychology 2006 Fall;18(4):1037-53. Ed: This is a frightening result. There is the concern that such a switch is increased by the use of stimulant medications. Stimulants Probably Don't Help School Performance While stimulants are definitely the favorites of many teachers, parents, students, pediatricians, and psychiatrists, I prescribe them only with hesitation. I prefer to try non-medication approaches first, then non-stimulant medications, and then, lastly, stimulant medications. Stimulants definitely help with concentration and on-task behavior for short periods of time. However, how much of the extra learning is retained long-term is an important question. With addictive drugs, some memory is state-dependent, i.e., it tends to be forgotten more readily that material learned while not on addictive drugs. The only review I have found on the issue is that little or no long-term academic benefit actually occurs. The National Institute of Health also makes a clear statement. National Institute of Health Consensus Panel Concludes the Evidence Shows Little Academic Improvement: "Of concern are the consistent findings that despite the improvement in core symptoms, there is little improvement in academic achievement or social skills....There is no information on the long-term outcomes of medication-treated ADHD individuals in terms of educational and occupational achievements, involvement with the police, or other areas of social functioning." Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder. NIH Consens Statement 1998 Nov 16-18; 16(2): 1-37. Only Lowest Ritalin10 mg Dose Associated with Academic Improvement in Two Studies: A 6-week PC DB study of 45 ADHD children given 10 mg, 20 mg, and 30 mg per day found that overall academic improvement occurred with the lowest dose but no additional improvement came with increasing doses. Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD. Evans SW, Pelham WE, et al. Exp Clin Psychopharmacol. 2001 May;9(2):163-75. A replication with 36 children ages 5-6 found the same thing at 0.3 and 0.6/mg/kg. J Am Acad Child Adolesc Psychiatry. 2005 Mar;44(3):249-257. Ed: This study focused on short-term learning on daily quizzes and in-class behavior. Whether there is any long-term learning boost remains to be seen. Review of 78 Studies Finds No Impact on Academic Improvement: A McMaster University review of the research looked at the most scientific studies that have been done on the treatment of ADHD. Few differences were found between the various stimulants. Research comparing stimulants and tricyclics was inconclusive. Non-drug interventions didn't do as well as stimulants and didn't add much to medications when combined. Stimulants may have behaviorally, but they have no positive impact on academic achievement. Treatment of attention-deficit/hyperactivity disorder. Jadad AR, Boyle M, et al. Evid Rep Technol Assess (Summ). 1999 Nov;(11):i-viii, 1-341 No Academic Benefit Found with Inattentive ADHD Stimulant Treatment: Although psychostimulants showed a short-term decrease in symptoms in students diagnosed with predominantly inattentive ADHD, they did not significantly improve grade-point averages. In a 1-year study of 32 students put on methylphenidate, the GPA of only 5 students improved. When compared to the GPA changes in the previous year, this was not a significant change (p = .174). ADHD treatment and academic performance: a case series. LH McCormick, J Fam Prac Aug/03. Ed: Obviously, this was not controlled research. Uncontrolled studies traditionally find more favorable results and then over-interpret these results. Methylphenidate and Adderall Said to Help Academically But No Measures: A PC DB crossover study by SUNY-Buffalo for only 6 weeks with only 25 children report that the two stimulants "produced dramatic improvements in rates of negative behavior, academic productivity, and staff/parent ratings of behavior." There were two different dosages of the two medicines which changed daily in random fashion over a total of just 24 days. The only measures of academic productivity were ratings by teachers and no standardized testing or academic testing showing improved performance in comparison to non-ADHD peers. And 25% were called non-responders. There was a concurrent uncontrolled behavioral intervention. A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pelham WE, Aronoff HR, et al. Pediatrics. 1999 Apr;103(4):e43. (Ed: The authors draw powerful conclusions that seem inappropriate based on their very small and very brief study with many variables and limited measures. I don't know why they use the brandname for methylphenidate, since it is widely available as a generic, unless it is a favor to the pharmaceutical company who supplied the medicine and possibly the funding.) Intensive Academic and Psychotherapy Program No Benefit: In a 2-year study of 103 ADHD children ages 7-9, (1) methylphenidate alone, (2) methylphenidate plus psychosocial treatment that included academic remediation, organizational skills training, and psychotherapy as well as parent training and counseling and social skills training, or (3) methylphenidate plus attention control treatment were compared academically and for depression and self-esteem. There was no advantage was found on any measure of academic performance or emotional status for the combination treatment. There are a handful of short term studies that report academic benefit, but I have not found many one-year plus studies that carefully address this issue. I have not done any in depth evaluation as was done by Jadad et al above in his review of 78 studies in which the researchers carefully examined 41 different factors in many studies, so I have to assume that his conclusion is a reasonable one. Also, I did find this old 1981 study below to be interesting and troubling in its conclusion. Are Benefits Short-Lived? Methylphenidate Said Effective in Beginning But Little Long-Term Benefit: 62 children were reevaluated four years after their initial screening. They had been treated with varying durations of stimulant medication for ADHD ranging from 6 months to 4 years. After four years, behavioral and social difficulties tended to improve, but not academic ones. There were no group differences on outcome measures. Based on these findings, the researchers concluded that the main benefit of methylphenidate occurred during the first month and that there was no measurable long-term effect apparent four years later. A four-year follow-up study of the effects of methylphenidate on the behavior and academic achievement of hyperactive children. Charles L, Schain R. J Abnorm Child Psychol. 1981 Dec;9(4):495-505 Although the modern tendency is to speak of hyperactivity as being a life-long disorder continuing from before age seven until well into adulthood, very few stimulant medication studies follow youth for more than a couple months. Of the few studies lasting one year or longer, the results are very mixed with most agreeing with the above study. I am a bit perplexed. If the available evidence doesn't show any clear long-term academic benefit and if even behavioral benefits may be minor, it certain weakens the case for the treatment in the first place. I see very few physicians using well proven vitamin and mineral therapy to increase childhood intelligence, although this is very well proven with a modest but real benefit. I can't get myself to accept that there are no significant harmful benefits from many years of stimulant medication, although I haven't seen reports of any. Huge companies are making billions on stimulants and buying lots of influence in major teaching centers and physician offices, but the independent proof of benefit is lacking. Stimulants should be used much more sparingly in my opinion. Do Stimulants Cause Mania? Stimulants May Cause Mania in Many ADHD Children: The onset of mania was linked temporally in 21% of 82 juveniles to the starting stimulant medication. Faedda GL, Glovinski IP, Austin NB et al. Treatment emergent mania in pediatric manic depressive illness: role of antidepressants and stimulants. Presented at the 1st annual Pediatric Bipolar Disorder Conference; March 21-22, 2003; Washington, DC. (Ed: This is a preliminary report, but its findings are very worrisome.) Anti-Depressants May Be Worse: Researchers reviewed all consecutive admissions with a diagnosis of bipolar disorder to a university-affiliated children's hospital, and collected information regarding previous exposure to antidepressants and stimulants. The mean age of diagnosis of bipolar disorder in our cohort was 12. Children who received prior antidepressant and/or stimulant treatments had an earlier bipolar diagnosis (age 10.7) than children never exposed to these medications (12.7; p = .099). Stimulants appeared to be tolerated for a longer duration than antidepressants (55 months vs. 6.7 months, p = .0001). Children exposed to antidepressants appear to be diagnosed with bipolar disorder earlier than those never exposed to these medications. Antidepressant exposure in bipolar children. Cicero D, El-Mallakh RS, et al. University of Louisville School, Kentucky. Psychiatry. 2003 Winter;66(4):317-22. Ed: Unfortunately, I don't know how many children were in this study. Small, retrospective studies are much less reliable. Stimulants for ADHD Appear to Have Made Later Mania Worse: In a small retrospective study of 80 adolescents hospitalized with Bipolar disorder, manic or mixed, assessed severity of hospital course, and compared groups according to current/past stimulant or antidepressant treatment, the lifetime ADHD rate was 49%; 35% of patients had exposure to stimulants and 44% to antidepressants. Stimulant-exposed patients were younger than non-exposed (13.7 vs. 15.1, P=0.002). Only stimulant exposure was associated with worse hospitalization course (P=0.02). Stimulant-exposed BP-adolescents may have more severe illness course not fully explained by ADHD comorbidity. Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment. Soutullo CA, DelBello MP, et al. University of Cincinnati. J Affect Disord. 2002 Aug;70(3):323-7. Amphetamines Used on Bipolar Children: An 8-week open-label trial of divalproex (Depakote) to control manic symptoms in 40 bipolar children ages 6-17 with mania and ADHD symptoms was followed by a 4-week DB PC crossover of added mixed amphetamine salts was safe and effective for treatment of ADHD symptoms. With divalproex sodium, 32 subjects achieved > or =50% reduction in Young Mania Rating Scale baseline scores, but only three participants had significant improvement in ADHD symptoms. For the 30 subjects who entered the placebo-controlled crossover trial, mixed amphetamine salts was significantly more effective than placebo for ADHD symptoms. No significant side effects or worsening of manic symptoms was observed. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Scheffer RE, Kowatch RA, et al. University of Texas Southwestern Medical Center at Dallas. Ed: I am very skeptical of this brief 4-week study of amphetamines for bipolar children. First of all, I would not have used Depakote in view of its higher suicide rates vs. lithium. Then I would have tried non-medication interventions for ADHD, at least initially. Amphetamines can certainly increase psychotic symptoms and 4 weeks might not be long enough to detect the damage. Since stimulants don't help academic achievement in carefully done studies, their benefits may not be as great as commonly believed. Case: Acute Psychosis Associated with Therapeutic use of Dextroamphetamine: A 7-year-old given Adderall for ADHD became agitated with visual hallucinations. Calello DP, Osterhoudt KC. Pediatrics. 2004 May;113(5):1466. (Letter). Cherland and Fitzpatrick, Canadian Journal of Psychiatry, 44:811-813, 1999, reported that 6% of 98 children treated with methylphenidate developed psychotic symptoms during treatment for ADHD (these children were probably very carefully interviewed for any symptoms. However, hallucinations was one symptom reported). A 24-year old was acquited after killing his five- week old daughter and being found not to be criminally culpable due to an Adderall-induced psychotic state (AP,October 25,1999). Amphetamine Can Cause Psychosis in Primates: Repeated amphetamine (AMPH) exposure in nonhuman primates produces a chronic state of monoamine dysregulation and long-lasting changes in behaviors elicited by acute AMPH (including tracking, grasping "at thin air," manipulating nonapparent stimuli, and hypervigilance) that bears a marked resemblance to symptoms of amphetamine psychosis. The pre-frontal cortex was found to be malfunctioning. Castner SA, et al. Yale, Biol Psychiatry. 2003 Jul 15;54(2):105-10. Amphetamine Cause Mania in Rats via Oxidative Stress: Previous studies have suggested that oxidative stress may play a role in the pathophysiology of bipolar disorder (BD). Lithium and valproate exert neuroprotective effects against oxidative stress. Adult male Wistar rats received d-amphetamine (to cause mania) or saline for 14 days, and between the 8th and 14th days, they were treated with lithium, valproate or saline. In the second model (prevention treatment), rats were pretreated with lithium, valproate or saline, and between the 8th and 14th days, they received d-amphetamine or saline. Lithium and valproate reversed (reversal treatment model) and prevented (prevention treatment model) amphetamine-induced hyperactivity and reversed and prevented amphetamine-induced TBARS formation in both experiments. However, the co-administration of lithium or valproate with amphetamine increased lipid peroxidation, depending on the brain region and treatment regimen. No changes in protein carbonyl formation were observed. SOD activity varied with different treatment regimens, and CAT activity increased when the index of lipid peroxidation was more robust. Lithium and valproate exert protective effects against amphetamine-induced oxidative stress in vivo, further supporting the hypothesis that oxidative stress may be associated with the pathophysiology of BD. Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. Frey BN, et al. Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. J Psychiatry Neurosci 2006 Sep;31(5):326-32. Case: Acute Psychosis in 12-year-old from Adderall: A 12-year-old girl with symptoms of ADHD and a family history of ADHD but no other mental illness became psychotic after 5 weeks on Adderall. She did not sleep for 2 days with agitation, would not eat or drink, displayed bizarre behavior, and would not groom herself. She was evaluated and admitted having visual hallucinations (bugs crawling on the walls). Her speech was slow and her thought was tangential. She was hospitalized and found intermittently oriented to person, place, time, and situation. She had flight of ideas, tangential thought, a flat affect, psychomotor retardation, loss of short-term memory, and extremely poor hygiene. She also displayed magical thought, describing a personal acquaintance with characters from Greek mythology, and described visual hallucinations: disembowelment of her baby brother and bugs crawling on the walls. She had command auditory hallucinations instructing her to “stab holes in [her] brother,” she had tactile hallucinations of bugs crawling under her skin, and she displayed waxy flexibility. Adderall-induced psychosis in an adolescent. She recovered at 7 days. Surles LK, May HJ, Garry JP. Brody School of Medicine at East Carolina University, J Am Board Fam Pract. 2002 Nov-Dec;15(6):498-500. Case Reports on FindLaw Website: One mother reports her 3-year-old son was prescribed Adderall and after the first dose of 5 mg. developed severe visual hallucinations treated with an anti-psychotic risperidone. Patricia Bonnell 6/25/03; ; http://boards.lp.findlaw.com/cgi-bin/[email protected]%[email protected]/528 Cases of Adderall Psychosis in Children Reported by Family on www.ablechild.org : One grandfather reports his grandson, whom he was apparently raising, after taking only 6 doses once a day of Adderall caused him to complain of feeling like a statue. Shortly thereafter, the grandson stated that he was heard voices, feels like he was someone else, like in a dream, and was seeing things. The reaction appears to have resolved slowly. Posted by Jim Paicos on Aug 11 2004. http://www.ablechild.org/board/?topic=topic1&msg=6425 Methylphenidate (Ritalin) Low Dose Treatment Best for Teen Academics: 45 ADHD students DB PC crossover during 6 week study with three different dosages of methylphenidate. 10 mg methylphenidate did better than higher dose or placebo in teen students with ADHD. Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD. Evans SW, Pelham WE, Smith BH, Bukstein O, Gnagy EM, Greiner AR, Altenderfer L, Baron-Myak C. Exp Clin Psychopharmacol 2001 May;9(2):163-75 Methylphenidate Helps Conduct Disorder with or without ADHD: 6-15yos 83 pt. 31% conduct disorder alone, 69% conduct disorder plus ADHD. 74 completed trial 5 weeks. Considerably better by parents, teachers, psychiatrists, and trained classroom observer on nearly all measures of conduct disorder. Less cruelty, less obscene language, less property destruction, less stealing. Mothers rates 78% globally improved vs. 27% placebo. Similar differences for other groups. Improvement of aggressive behavior not associated with level of initial ADHD. Klein R, et al: Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Arch Gen Psyc 97;54:1073-80. NIMH funded Long Island Jewish. Methylphenidate Helps School Behavior of MR-ADHD: 24 pt DB PC crossover at 0.15, 0.30, and 0.60mg/kg/d. Average age 11. The most significant improvements occurred at the 0.60 mg/kg methylphenidate dose for teacher ratings of inattention ( =.024), hyperactivity ( <.001), aggression ( <.001), and asocial behavior ( =.009). No significant improvements, relative to placebo, occurred at the 0.15 mg/kg dosage. Of interest, nearly all significant medication-related behavioral improvements were detected by teachers. However, parents were sensitive raters of side effects, noting more sleeping problems and loss of appetite at the 0.60 mg/kg. Treatment Effects of Methylphenidate on Behavioral Adjustment in Children With Mental Retardation and ADHD. Pearson DA, Santos CW, Roache JD, Casat CD, Loveland KA, Lachar D, Lane DM, Faria LP, Cleveland LA. J Am Acad Child Adolesc Psychiatry 2003 Feb;42(2):209-216 DNA Damage Caused by Methlphenidate; May Cause Cancer!: In 12 children on methylphenidate, peripheral blood lymphocytes were obtained before and three months after starting the drug. In all participants, treatment caused a significant 3, 4.3 and 2.4-fold increase in chromosome aberrations, sister chromatid exchanges and micronuclei frequencies, respectively (P=0.000 in all cases). There is a well-documented relationship between elevated frequencies of chromosome aberrations and increased cancer risk. Cytogenetic effects in children treated with methylphenidate. El-Zein RA, et al. University of Texas M.D. Anderson Cancer Center. Cancer Lett 2005 Dec 18;230(2):284-91. Drug Abuse: Methylphenidate Said to Reduce Risk: 4 of 6 long-term follow-up studies find less drug abuse later and one found more. That one by Nadine Lambert, a UC Berkeley psychologist, found a later increased usage of cocaine. She followed 492 children for 30 years. They had been treated with stimulants or untreated. In the Wilens meta-analysis, untreated ADHD children have about twice the risk of substance abuse as non-ADHD kids while treated children approached the same level as that of non-ADHD kids. A random-assignment prospective study of the issue is underway in Germany. 1.5 million US kids on stimulants. Timothy Wilens, child psychiatrist at MGH/Harvard, Pediatrics 1/6/03, reviewed six studies of 674 ADHD kids on stimulants and 360 untreated controls followed four or more years into late adolescence or early adulthood and looked at tobacco, alcohol, marijuana and other drugs.; A 7th study was added to the meta-analysis. Authors report a 50% decrease in the risk of substance abuse bringing the expected level down to within the range of the normal population. Does stimulant treatment lead to substance use disorders? Faraone SV, Wilens T. J Clin Psychiatry. 2003;64 Suppl 11:9-13 Drug Abuse: Methylphenidate Said to Reduce Risk: A longitudinal follow-up of 176 children and adolescents found that, after controlling for conduct disorder, that children treated with methylphenidate had no higher levels of substance abuse later and high school students actually had a lower rate of hallucinogen abuse. Childhood stimulant treatment and risk for later substance abuse. U. Wisc. Milwaukee. Fischer M, Barkley RA. J Clin Psychiatry. 2003;64 Suppl 11:19-23 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. Tics: Methylphenidate Didn’t Cause Tics in DB: 91 pt in 1 year DB PC study. Some had non-severe tics in beginning. Many PC patients were switched to MPH during year due to inability continue with placebo. MPH 0.5 mg/kg bid. 19% and 16% developed tics and 33% of those with tics in each group showed progression. Toronto. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? Law SF, Schachar RJ. J Am Acad Child Adolesc Psychiatry 1999 Aug;38(8):944-51 Growth Retardation Half-inch Per Year: A study of 140 ADHD children (age 4.4)(average methylphenidate, 14.2 mg/day) found that during treatment, slopes were significantly (p<.0001) less than zero for z height (-0.304/yr) and z weight (-0.530/yr), indicating reduction of growth rates. For 95 children who remained on medication, annual growth rates were 20.3% less than expected for height (5.41 cm/yr-6.79 cm/yr=-1.38 cm/yr) and 55.2% for weight (1.07 kg/yr-2.39 kg/yr=-1.32 kg/yr). Stimulant-related reductions of growth rates in the PATS. Swanson J, et al. University of California, Irvine. . J Am Acad Child Adol Psychiatry 2006 Nov;45(11):1304-13. Growth Retardation with Methylphenidate: It is still a controversy whether methylphenidate causes any permanent loss of tallness or whether the growth delay is only temporary with catch up during vacations from methylphenidate and its discontinuation in teenage year. This study reports on 84 children who continued to show evidence of growth retardation when compared to their siblings after 2 years of treatment. Yale. Daily methylphenidate use slows the growth of children: a community based study. Lisska MC, Rivkees SA. J Pediatr Endocrinol Metab. 2003 Jun;16(5):711-8 Growth Retardation Not Found in ADHD Girls: A Harvard study of 124 ADHD girls found no growth retardation associated with medication treatment. Of interest, ADHD girls with depression 16.5 pounds more than ADHD girls without depression. Growth deficits and attention-deficit/hyperactivity disorder revisited: impact of gender, development, and treatment. Biederman J, Faraone SV, Monuteaux MC, Plunkett EA, Gifford J, Spencer T. Pediatrics. 2003 May;111(5 Pt 1):1010-6 Treatment Might Lower Smoking Risk: From a community sample of 511 adolescents participating in a longitudinal health study, 27 were identified as having ADHD, and 11 of these were receiving pharmacotherapy. Self-report surveys, electronic diaries, and salivary cotinine all indicated that adolescents treated with pharmacotherapy for ADHD smoked less than their untreated counterparts over 2 years of high school. Univ Calif Irvine. Is there a link between adolescent cigarette smoking and pharmacotherapy for ADHD? Whalen CK, Jamner LD, Henker B, Gehricke JG, King PS. Psychol Addict Behav. 2003 Dec;17(4):332-5 Pre-Schoolers: Benefit Minor: In the DB PC NIMH Preschool ADHD Treatment Study (PATS) of 165 children (age 4.4), significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. Greenhill L, et al. Columbia University. . J Am Acad Child Adol Psychiatry 2006 Nov;45(11):1284-93. 0.30 and 0.60mg/kg Worked Best in Retarded: A DB PC study of 24 mentally retarded children with ADHD using doses of 0.15, 0.30, and 0.60 mg/kg/d found teachers noted improvement in classroom on the two higher dosages. Teachers reported decreases in inattention, hyperactivity, aggression, and asocial behavior. Parents did not note any improvement at home although they noted increased problems with insomnia and loss of appetite on the two higher dosages. Treatment effects of methylphenidate on behavioral adjustment in children with mental retardation and ADHD. Pearson DA, Santos CW, Roache JD, Casat CD, Loveland KA, Lachar D, Lane DM, Faria LP, Cleveland LA. J Am Acad Child Adolesc Psychiatry. 2003 Feb;42(2):209-16. O.25 and 0.50 mg/kg Differing Effects: 60 ADHD children aged between 8 and 12 years completed a randomized DB PC crossover trial with two doses of methylphenidate (0.25 and 0.5 mg/kg body weight. intensity-dimension functions are best influenced by higher doses, executive functions by moderate doses, and selectivity-dimension functions by variable doses. In addition, divergent results from behavior rating scales and from attentional paradigms emphasize that clinicians have to decide what constitutes an appropriate clinical response. Differential Effects of Methylphenidate on Attentional Functions in Children With Attention-Deficit/Hyperactivity Disorder. Konrad K, Gunther T, Hanisch C, Herpertz-Dahlmann B. J Am Acad Child Adolesc Psychiatry. 2004 Feb; 43(2): 206-214 Methylphenidate Helps But Serious Problems Remain: After a PC DB trial of methylphenidate for 52 children with borderline to moderate mental retardation and ADHD, 69% of ADHD youth continued on medication. 72% showed some improvement, but two-third continued to test above the 98th percentile in hyperactivity and 22% had to be hospitalized despite the medication during the next 12-65 months. Those with Conduct Disorder fared worse. Univ. Pittsburgh. Long-term follow-up of children with mental retardation/borderline intellectual functioning and ADHD. Handen BL, Janosky J, McAuliffe S. J Abnorm Child Psychol. 1997 Aug;25(4):287-95 Side-Effects: Stimulants Increase Blood Pressure: In a study of 17 children using ambulatory BP monitoring, two subjects (1 Adderall, 1 methylphenidate) met the criteria to be considered hypertensive based both on mean awake and 24-hour blood pressure load assessments during their on-treatment period. Positive correlation coefficients (p < 0.05) were found when comparing stimulant dose (mg/kg) with the percent change of mean SBP, DBP, and heart rate between off and on therapy (r = 0.56, 0.61, and 0.58, respectively). U Arkansas. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Stowe CD, Gardner SF, Gist CC, Schulz EG, Wells TG. Ann Pharmacother. 2002 Jul-Aug;36(7-8):1142-9 Stimulant Rebound Can Mimic Bipolar: 7yo girl treated with a stimulant for ADHD didn't do well and appeared to have bipolar disorder and the treated with meds for it. A reevaluation led to a discontinuation of bipolar meds and use of longer-acting stimulant. The girl did better. George Washington Univ. Can stimulant rebound mimic pediatric bipolar disorder? Sarampote CS, Efron LA, Robb AS, Pearl PL, Stein MA. J Child Adolesc Psychopharmacol. 2002 Spring;12(1):63-7 Omitting Weekend Methylphenidate (Ritalin) Reduces Side-Effects Without Loss of Benefit: In a 28-day DB PC study of 40 children, half received placebos during the weekend. Both groups showed a significant reduction on the ABRS hyperactivity scores over time as the dose was increased. However, the group difference in the ABRS scores was not statistically significant, either on weekend parent ratings or on teachers' ratings. The omission of MPH on weekends was associated with significantly less severity of insomnia ( p = 0.05) and a trend for less interference on appetite ( p = 0.08). Weekend holidays during methylphenidate use in ADHD children: a randomized clinical trial. Martins S, Tramontina S, Polanczyk G, Eizirik M, Swanson JM, Rohde LA. University of Rio Grande do Sul, Porto Alegre, Brazil. J Child Adolesc Psychopharmacol. 2004 Summer;14(2):195-206 Stimulant Abuse Common on Campus: In interviews with 381 college students at the University of Wisconsin-Eau Claire, 17% of men and 11% of women reported illicit use of prescribed stimulant medication. Of surveyed students, 44% stated that they knew students who used stimulant medication illicitly for both academic and recreational reasons. Students reported they experienced time pressures associated with college life and that stimulants were said to increase alertness and energy. Regression analysis revealed that the factor that predicted men's use was knowing where to get easily acquired stimulant medication, whereas the main predictor for women was whether another student had offered the prescribed stimulants. Illicit use of prescribed stimulant medication among college students. Hall KM, Irwin MM, et al. University of Wisconsin-Eau Claire. J Am Coll Health. 2005 Jan-Feb;53(4):167-74. Stimulant Abuse Causes Long-Term Attention Problems: In a study of 50 twin pairs in which only 1 member had heavy stimulant abuse (cocaine and/or amphetamines) ending at least 1 year before the evaluation, abusers performed significantly worse than nonabusers on functions of attention and motor skills, although did well on visual vigilance. A twin study of the neuropsychological consequences of stimulant abuse. Toomey R, Lyons MJ, et al. Harvard. Arch Gen Psychiatry. 2003 Mar;60(3):303-10. Adderall Adderall is a mixture of amphetamine salts. Amphetamine were once used as diet pills, but quickly became popular drugs of abuse call "speed." My impression is that around Penn State University where I live, student abusing stimulant medications prefer Adderall to methylphenidate. My concerns about methylphenidate are magnified with Adderall. Adderall XR Banned in Canada: Because of reports of 14 sudden deaths in children and 6 in adults reported to the FDA and in other countries. There are also 12 strokes reported, two in children. Canada has decided to ban the drug. The U.S. FDA says that the rate of sudden death based on the 30 million prescriptions written between 1999 and 2003 does not appear to be increased over the expected rate without Adderall. The manufacturer has notified physicians. Unfortunately, the manufacturer didn't say how many deaths have been reported to the FDA. Adderall already carries a warning of sudden death in patients with structural cardiac abnormalities and a warning about misuse of amphetamines. The FDA also warns of worsening mental illness (psychosis). http://www.fda.gov/cder/drug/InfoSheets/patient/adderallPT.htm The manufacturer, Shire US, issued a Feb. 11, 2005, "Dear Doctor" letter to American physicians, among other things noting, "A side effect seen with the amphetamine class is psychosis." 30 million monthly prescriptions might mean only 1 million children and adults taking the medicine for an average of 2 1/2 years. That's one death per 50,000. Sudden death is very rare in children, so I would think that most of those deaths are due to the medication. I have not heard the same concern with methylphenidate. Theophylline Theophylline Research for ADHD: In a 6-week, 32-child DB ADHD study of theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2), there was no significant differences between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores and no significant difference in amount of side-effects. Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial. Mohammadi MR, Kashani L, et al. Tehran University. J Clin Pharm Ther. 2004 Apr;29(2):139-44 Modafinil Modafinil Helped a Little in Small DB: A very small 24 child ADHD DB PC study found a 12% decrease in the Connor's ADHD Rating Scale with modafinil vs. 2% decrease with placebo. The study lasted only 5-6 weeks. Modafinil (Provigil) Better than Placebo, But Extremely Expensive with Stimulant Type Side-Effects: In a 9-week DB PC study of 248 children with ADHD, ADHD symptoms decreased by 15.0 points vs 7.3 for placebo (effect size: 0.69). Significant improvements were observed with modafinil on the ADHD-RS-IV School and on Home Versions at week 1, with improvements maintained throughout the study. Modafinil reduced inattention and hyperactivity-impulsivity. 48% of modafinil-treated patients were rated as "much" or "very much" improved vs. 17% for placebo. Modafinil caused insomnia (29%), headache (20%), and decreased appetite (16%). Thomas E. Radecki, M.D., J.D. modern-psychiatry.com Email: [email protected]
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