Does Chronic Ritalin Use Increase Risk Of Cancer?
Does Chronic Ritalin Use Increase Risk Of Cancer?
Sam Goldstein, Ph.D.
This is a SamGoldstein.com Monthly Article - April, 2005
Copyright © 2005 Dr. Sam Goldstein - All Rights Reserved
Does chronic use of Ritalin at doses given to children to treat ADHD increase chromosomal abnormalities and in doing so increase future risk of developing cancer? In this month's web article, Dr. Goldstein provides a brief overview of cancer and cancer risks and reviews a just published study addressing this issue in an effort to provide a reasoned, reasonable and scientific perspective on this potentially inflammatory issue.
Cancer is defined in Miriam-Webster's Collegiate Dictionary as "a malignant tumor of potentially unlimited growth that expands locally by invasion and systemically by metastasis." Cancer spreads destructively. There are literally dozens of different types of cancer, many of which, despite their beginnings, can eventually affect most if not all organs and systems in the body. In 2002, the American Cancer Society estimated that the life time probability that a male would develop cancer was one out of two; for women, one out of three. For males the leading cancers are prostate, lung, colon and rectum; for women, leading cancers are breast, lung, colon and rectum. In 2002, cancer was reported to be the second leading cause of U.S. mortality, accounting for 23% of all deaths and over a half million people. As a comparison in that year, unintentional death from accident accounted for only 4?% with Alzheimer's disease accounting for 2?%. Lung cancer is the leading cause of cancer deaths. Consumption of tobacco has been significantly implicated in lung cancer. According to the American Cancer Society the more a person smokes the more likely they may develop lung cancer. Further, the more a person consumes alcohol the higher his or her risk of getting certain cancers. Combining tobacco with alcohol drives the risk even higher. For example, quitting tobacco and limiting alcohol sharply reduces many risks of oral cancer even after many years of use. It has also been suggested that eliminating tobacco could nearly wipe out lung cancer. It has been estimated that if Americans ate a healthy, balanced diet, emphasizing vegetables, fruits, whole grains and beans as well as maintaining a healthful weight, as many as one third of all cancer deaths in the United States could be prevented. Wearing protection to avoid damage to cells from the sun can also limit skin cancers. Better industrial control of toxins and other chemicals considered carcinogens that workers may be exposed to over time such as asbestos can also significantly reduce the incidence of cancer. For example, long term exposure to urban air pollution from traffic has been found to contribute to chromosomal damage. Bus drivers have been shown to have a significantly higher frequency of cells with chromosomal aberrations as compared to postal workers.
Consider that between 1950 and 2002 rates of heart disease decreased by half, cerebral vascular disease by two thirds and pneumonia/influenza by over half. Yet during this very same period of time, the incidence of cancer has remained constant. This despite the fact that five year survival rates for children through age fourteen with cancer since 1974 has increased by 100%. It may be that as we come to understand and eliminate some risks of cancer we introduce new ones into our environment or we have developed more effective treatments. Much more research is needed in our efforts to understand and interpret the relationship between certain genotypes, biomarkers of exposure and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens.
Attention Deficit Hyperactivity Disorder
Between 1990 and 1993, according to a study published in the New England Journal of Medicine, ADHD related visits of children to primary care doctors in the United States increased from 1.7 to 4.2 million visits per year. Ninety percent of those children were treated with medications. Seventy-one percent of those were central nervous system stimulants such as methylphenidate. According to congressional testimony, more than ten million prescriptions were written for methylphenidate in 1996. Domestic sales of methylphenidate in the United States showed an increase of almost 500% between 1991 and 1999, a trend that has continued. Methylphenidate and other stimulants are probably the best studied psychiatric medications with literally hundreds of research studies evaluating symptom relief, side effects and issues related to outcome. When used appropriately in therapeutic doses, methylphenidate and other stimulants have been reported to be effective, generally safe and to cause minimal short and long-term side effects. The benefits in improved daily functioning leading to a reduction in a host of daily psychiatric, emotional, behavioral and educational impairments experienced by children with ADHD have been well documented. It has also been reasonably documented that symptom relief may not necessarily equate to positive or powerful change in long-term outcome. That is, stimulants like methylphenidate may reduce immediate symptoms and impairment for individuals with ADHD but as those individuals transition into adulthood the medication though seemingly necessary may not be sufficient alone to lead to a normalization of functioning throughout life.
Methylphenidate and Cancer
There is a well documented relationship between elevated frequencies of certain chromosome abnormalities and increased risk of cancer. A host of environmental phenomena can cause abnormalities in the chromosomes of single cells which may increase the risk for developing different kinds of cancers. Keep in mind that when a single cell's chromosomes are adversely affected, this does not necessarily mean that all cells in the body are affected. Although methylphenidate, marketed as Ritalin?, Concerta?, Metadate? and Methylin?, has not been found to cause mutations in bacteria, rat or mouse cells grown in culture (in a petri dish), increases in chromosomal abnormalities have been reported with methylphenidate in some animal studies.
It is my understanding that for a medication to be approved for use by the Federal Drug Administration a p_harmaceutical company must demonstrate that there is no risk the medication could cause chromosomal abnormalities or cancers. Yet, considering that methylphenidate has been approved for human use for over fifty years and in particular the significant number of children and adults taking methylphenidate and other stimulants, there have been few studies on the potential for these drugs to cause chromosomal abnormalities or lead to increased risk of cancer.
This is reported to be the primary motivation for researchers Randa L. El-Zein and colleagues at the University of Texas, Anderson Cancer Center, to examine the cytogenetic effects in children treated with methylphenidate. Their study has just been published in the Cancer Letters, a peer-reviewed journal published by Elsevier Ltd. The authors identified twelve children meeting the Diagnostic and Statistic Manual - Fourth Edition of the American Psychiatric Association criteria for ADHD, taking methylphenidate in daily doses between 20 and 54 mgs. per day. Because of the small number of subjects a medication free group was not used. Instead, each child was used as his or her own control. Chromosomal abnormalities in blood cells were measured before starting the methylphenidate and then after three months of taking the medication. Three chromosomal abnormalities: chromosome aberration, sister chromatid exchanges, and micronuclei frequencies were evaluated. The authors opine that greater frequencies of these aberrations, equate with an increased potential for cancer.
The authors report that, "In all participants, treatment induced a significant 3, 4.3 and 2.4-fold increase in chromosome aberrations, sister chromatid exchanges and micronuclei frequencies respectively." These findings were statistically significant in every single child. Though it is well documented that the frequencies of chromosomal abnormalities in these blood cells is a relevant biomarker for cancer risk in humans, it is unclear whether this level of increased risk would actually translate into a statistically significant increase in future cancers in a population of children taking methylphenidate on a long-term basis.
The authors further report that, "Our results, coupled with the positive cancer bio-assay data in laboratory animals provide a strong argument that methylphenidate should be further investigated." The authors raise questions about the potential reversibility of this problem when the medication is stopped and whether alternative stimulants might have the same adverse impact. The authors conclude, "The lack of research on the long-term effects of methylphenidate use in humans warrants great concern. At present it is not clear what the long-term effects would be for children who took methylphenidate ten or twenty years ago, or for those who are currently being treated with this drug."
In response to the publication of this paper, the non-profit organization Children and Adults with Attention Deficit Disorder has issued a statement in which they encourage individuals with ADHD and their families to seek answers to questions about this issue from their physicians and urge Directors of the National Institute of Mental Health, the National Cancer Society and methylphenidate manufacturers to fund additional studies in an effort to provide definitive information about this issue. It is, I believe, the responsibility of all mental health professionals to support and endorse this position.
I am concerned, however, that until these studies are completed and the patient work of science understood, impatient individuals with personal agendas may cause significant public controversy. In the interim, it is critically important that the public, as well as consumers of methylphenidate, possess accurate information about what this study means and what we know about cancer risks. I am concerned given that the treatment of ADHD, particularly the use of medications, has become a convenient topic for some groups and organizations to promote their own agenda, that it is only a matter of time before we begin hearing radio and television programs as well as seeing headlines and websites promoting that "Ritalin causes cancer", a phenomena that has not been proven by this study.
A scientific cause and effect link, while essential in clinical practice, unfortunately is not considered as important in the arena of public policy and the courts. Take for example the fact that the courts have seen dozens of civil and criminal cases in which the SSRI antidepressants have been claimed to cause suicidal or homicidal behavior. In some cases juries, absent strong scientific data, have chosen to accept this hypothetical link and rule in the favor of those making these claims. There are likely a significant minority of individuals who have or are taking stimulants and have during the course of their lives developed some type of cancer. It is only a matter of time before this link is touted in civil litigation. It is my hope that scientific studies can be generated to address this issue appropriately should these cases come to the court room.
Final Thoughts
As I described in my web article last month (Psychiatric Medications and Children), the number of areas in which there is a backlash against medication use in mental health is increasing. The risk of psychiatric drugs causing cancer is but another example. Yet measuring risk is complicated, even given our increasing technological sophistication. Until recently, there has been insufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of humans exposed to mutagens and carcinogens. As the field of molecular epidemiology develops, these questions will be answered. In the interim, how shall we as professionals respond? How shall we as a community respond? My suggestion can be summed in one word - honesty. We must make an honest effort as a field to inform our patents and clients as well as the community in general about the meaning of these emerging research studies, whether it be related to cancer risk, cardiac problems, suicide, or any other phenomena. I will discuss this study with parents and suggest they speak with their physicians. I will make an effort to help parents understand that increased risk of these markers does not necessarily equate to increased risk of cancer. I will do my part to encourage my professional organizations and colleagues to seek funding to address this issue. I will continue making an effort to help my patients understand the known risks and benefits of stimulant treatment for ADHD. I will encourage families and individuals to make decisions that they feel is best for them - not out of fear, anger or belief, but hopefully as the result of an understanding of the available facts. In the end, whether my patients and their families choose stimulant treatment for ADHD or not, I will stand by them. For if they are to be effective case managers of their conditions or those of their family members, I must be a supportive, available and professional consultant.
