Methylphenidate and amphetamine do not induce cytogenetic damage in lymphocytes of children with ADHD.
OBJECTIVE
In response to previously published findings of methylphenidate-induced chromosomal changes in children, this study was designed to determine whether methylphenidate- or amphetamine-based drugs induce chromosomal damage (structural aberrations, micronuclei, and sister chromatid exchanges) in peripheral blood lymphocytes of children with attention-deficit/hyperactivity disorder after 3 months of continuous treatment.


METHODS
Stimulant drug-naïve subjects, 6 to 12 years of age, in good overall health, and judged to be appropriate candidates for stimulant therapy based on rigorously diagnosed ADHD using DSM-IV criteria, were randomized into two open-label treatment groups (methylphenidate or mixed amphetamine salts). Each subject provided a blood sample before initiation of treatment and after 3 months of treatment. Pretreatment and posttreatment frequencies of chromosomal aberrations, micronuclei, and sister chromatid exchanges were determined for each subject.


RESULTS
Sixty-three subjects enrolled in the study; 47 subjects completed the full 3 months of treatment, 25 in the methylphenidate group and 22 in the amphetamine group. No significant treatment-related increases were observed in any of the three measures of cytogenetic damage in the 47 subjects who completed treatment or the 16 subjects who did not.


CONCLUSIONS
Earlier findings of methylphenidate-induced chromosomal changes in children were not replicated in this study. These results add to the accumulating evidence that therapeutic levels of methylphenidate do not induce cytogenetic damage in humans. Furthermore, our results indicate that amphetamine-based products do not pose a risk for cytogenetic damage in children.
Witt
Kristine L
KL
National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Triangle Park, NC 27709, USA. witt@niehs.nih.gov
Shelby
Michael D
MD
Itchon-Ramos
Nilda
N
Faircloth
Melissa
M
Kissling
Grace E
GE
Chrisman
Allan K
AK
Ravi
Hima
H
Murli
Hemalatha
H
Mattison
Donald R
DR
Kollins
Scott H
SH
D000662:Amphetamines / Q000627:therapeutic use / Q000633:toxicity*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000627:therapeutic use / Q000633:toxicity*; D002648:Child; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use / Q000633:toxicity*; D015162:Micronucleus Tests; D012854:Sister Chromatid Exchange
C090411:Adderall; D000662:Amphetamines; D000697:Central Nervous System Stimulants; C449521:SLI381; D008774:Methylphenidate