The Association between Medication for Attention-Deficit/
Hyperactivity Disorder and Cancer
Hans-Christoph Steinhausen, MD, PhD, DMSc,1,2,3and Dorte Helenius, MSc1
Objective: A study on chromosomal abnormalities has raised concerns that medication with methylphenidate (MPH) for
attention-deficit/hyperactivity disorders (ADHD) might increase the risk of cancer. We performed a rigorous test of the
association between cancer and MPH and other drugs used for ADHD, based on data from nationwide Danish registers.
Methods: Data were linked from five registers containing information on a total of 21,186 patients with ADHD, their drug
a control group of patients with ADHD who had never taken medication. Frequencies of cancer diagnoses in these groups
were compared. In addition, hazard risk (HR) ratios for developing cancer, and survival rates in these subgroups, were
Results: The mean observation time varied between 1.3 and 10.8 years for the various drugs. Cancer rates in the total group
amountedto1.27per10 000person-yearsbeforeandto4.33per10000person-years afteronset oftreatment.Thefrequency
of cancer was significantly higher (p=0.05) after than before medication only in the antipsychotics subgroup. Furthermore,
for mixed medication, the cancer frequency in a small subgroup was significantly higher (p<0.05) after onset of medication
than in the unmedicated subgroup. The Cox regression analysis indicated that none of the drugs represented risk factors,
whereas higher dose (p<0.001) and older age (p<0.05) were risk factors for developing cancer.
developing cancer is not substantiated by these findings in a large and representative sample, which had been diagnosed and
treated over a period of 17 years.
of the most frequent mental disorders with a worldwide av-
erage prevalence of 5.3% in children (Polanczyk et al. 2007) and
3.4–4.4% in adults, according to recent United States and inter-
national surveys (Kessler et al. 2006; Fayyad et al. 2007). All in-
ternational guidelines agree that treatment with stimulants and
methylphenidate (MPH), in particular, play a major role in the
long-term professional care of the affected patients (Banaschewski
et al. 2006; Pliszka 2007). Therefore, prescription rates for cen-
trally acting drugs are high in many developed countries, with a
tendency to increase over the recent past (Zito et al. 2008; Zoega
et al. 2011).
Recently, concern has been raised by a study of chromosomal
abnormalities in peripheral lymphocytes in a small group of 12
children taking daily doses of MPH of between 20 and 54mg, with
each child serving as his or her own control and no use of a
ttention-deficit/hyperactivity disorder (ADHD) is one
concluded that three chromosomal abnormalities, namely, chro-
mosome aberration, sister chromatid exchanges, and micronuclei
remained unclear whether this well-documented biomarker for
cancer risk would actually translate into an increased risk of future
cancer in children receiving MPH treatment over an extended time
period. Furthermore, the study by El-Zein et al. (2005) has been
criticized for its serious experimental shortcomings, and both dif-
ficulties of interpreting its results and the uncertainties of its im-
plications for public health have been emphasized (Preston et al.
2005; Jacobson-Kram et al. 2008).
Following the same strategy, a first replication study in 12
to MPH studied the cytogenic effects on peripheral lymphocytes
before and 3 months after initiating MPH treatment (Ponsa et al.
2009). This study revealed no evidence of chromosomal aberra-
tions in their sample. Further studies found no increased frequency
months of treatment (Walitza et al. 2007), in an enlarged sample of
1Research Division for Child and Adolescent Psychiatry, Aalborg Psychiatric Hospital, Aarhus University Hospital, Aarhus, Denmark.
2Clinical Psychology and Epidemiology, Institute of Psychology, University of Basel, Basel, Switzerland.
3Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
Volume 23, Number 3, 2013
ª Mary Ann Liebert, Inc.
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Address correspondence to:
Hans-Christoph Steinhausen; MD, PhD, DMSc
Research Unit for Child and Adolescent Psychiatry,
Aalborg Psychiatric Hospital,
Aarhus University Hospital, Denmark
MEDICATION FOR ADHD AND CANCER213