Ritalin was not the answer for Matthew

Followup to Associated Press Story of April 2000
 By Shula Edelkind, August 15, 2000
Links updated April 2006 & August 2011

Last March, while skateboarding like any other 14-year-old American boy, Matthew Smith, of Berkley, Michigan, fell over and died. What happened? His death touched off a controversy as Medical Examiner Ljubisa Dragovic, in spite of pressure to "find some other explanation," announced that the boy's death was caused by heart damage from 8 years of Ritalin use.

What followed was an Associated Press article carried by multiple newspapers careful to include the quotes of two psychiatric professionals - and no cardiologists - claiming that side effects of Ritalin are "not significant and do not include death" and even that Dragovic's conclusions and diagnosis were "unfounded."

The immediate reaction of many parents whose children take Ritalin or other stimulants was to worry. The Feingold Association Help-Line reported numerous calls and e-mails from frantic parents whose children had been experiencing weakness, fast heartbeat, even heart murmurs. Some of those families opted to try diet therapy to replace drug therapy at that time. Not long after, however, at a local CHADD meeting in Atlanta, and presumably at other ADHD support groups across the country, it was whispered from sources unknown that the boy had been taking other prescription drugs as well, that he had an underlying pre-existing heart disorder, and that he had complained of symptoms but was ignored. Now that they could attribute Matthew's death to other medications, a freak medical condition, or parental neglect, people calmed down.

Nevertheless, questions remain -- how calm should we be? Is the grapevine accurate? How much should we worry? How many other children really are at risk? Do we know how to tell when they are in trouble before it is too late? Now that children are beginning to use Ritalin earlier, at age 2 and 3, and are expected to remain on it many years, or even their entire life, has this risk increased? How many years can a child safely take this medication before it becomes unsafe? If symptoms become "clinically significant," is it too late? Is it reversible? Why did none of the news articles quote a pediatric cardiologist? Or ANY cardiologist? What does a psychologist know about the "clinical significance" of a heart symptom? How can a psychiatrist, without ever looking at the child's heart muscle, decide that a Medical Examiner's decision is wrong?

The original news stories are no longer available, but for those of you who did not read the original Associated Press story, you can get more information at the following links:

  1. Oakland Press original two articles, April 14, 15, 2000, via Wayback Machine
  2. Detroit Free Press article by Brian DIckerson, April 19, 2000 via Wayback Machine
  3. Ritalin Prescription Takes Life Of 14 Year Old by the father of Matthew Smith
  4. World Net Daily, May 7, 2000
What actually killed Matthew?

According to Dr. Dragovic, upon autopsy Matthew's heart showed clear signs of small vessel damage -- the type caused by stimulant drugs such as amphetamines and cocaine. The boy did not have a pre-existing heart defect or disease. The boy had not been taking other drugs, prescription or illegal. The boy's complaints had not been ignored by his parents.

Dr. Dragovic describes his job as law enforcement. He is in the business, he says, of "calling a crow a crow, and an elephant an elephant. This is where the buck stops." He said that the type of damage he observed in Matthew's heart indicated small blood vessel changes that are caused by long term stimulant medication. He explained that this is nothing like the artery blockage in older men with high cholesterol and heart disease. This is a particular type of damage seen commonly in people who have abused cocaine or other stimulants. He explained that stimulant drugs affect every part of the body that has adrenergic receptors. Once the changes occur, you are left with a heart that cannot respond to sudden increases in functional demands. These changes seen in the blood vessels that supply the heart muscle are not reversible.

Current Recommendations (as of 2000)

The American Heart Association (AHA) recommends that before beginning treatment with any psychotropic drugs, children should be carefully evaluated for "long QT" and other heart rhythm abnormalities. The doctor should also take "a careful history ... with special attention to symptoms such as palpitations, syncope (fainting) or near-syncope." All other medications should also be known, because medications that affect the heart or inhibit the P450 system [the enzyme system dealing with toxins, medications, etc.] could cause problems. A careful history is important. But think -- Do you know whether your child has ever had palpitations or a feeling of weakness? Has anybody in your family ever had such an experience? How would you know if you have a long QT measurement without having an electrocardiogram to find out?

According to the AHA, tricyclic antidepressant (TCA) drugs such as imipramine and desipramine not only increase heart rate, but also prolong the various intervals of the heartbeat, as measured by EKG. These drugs include Tofranil, Anafranil, Elavil, Norpramin, Triavil ... Although they are often used together with Ritalin, and reported to be safe by studies such as the Findling study below, the AHA recommends frequent EKG monitoring of TCA, especially in combination with Ritalin, in spite of the fact that Ritalin itself is reported to increase heart rate and blood pressure only to an "insignificant degree." The AHA is specific that in the absence of symptoms or history of pre-existing heart disease or heart rhythm abnormalities, the use of Ritalin alone does not require an EKG prior to use, nor any later cardiovascular monitoring.

Dr. Rosenberg, a child psychiatrist with Children's Hospital of Michigan, when asked whether a child should be tested for any type of heart condition before prescribing Ritalin, responded that "it is far more important that the child have a psychiatric assessment by a trained mental health care professional and be prescribed appropriately." However, Dr. Rosenberg added that "if a child experiences racing heart beat or weakness, or any other symptoms, the parents should notify the person prescribing the medicine." Dr. Dragovic agreed, adding that unfortunately, some children have been under follow-up by pediatric cardiologists but nothing has surfaced because the detection of these changes is difficult. "Small vessel damage is insidious and much harder to see than problems with the large arteries that can be resolved by by-pass surgeries," he said. "More sophisticated stress tests are needed for a physicians to attempt to diagnose small vessel disease."

John Cantwell, MD, Director of Preventive Cardiology and Cardiac Rehabilitation at Piedmont Hospital in Atlanta, frequently deals with young adult athletes and runners. When Dr. Cantwell sees high school athletes with ADHD on stimulant medications that have any problem such as chest discomfort, palpitations or racing heart beat upon exercising, he tries to get them off the drugs. He agrees a parent should be concerned if there are any such symptoms. "In general," he said, "if a parent called and said her son is on Ritalin and playing ball but his heart is racing, I would try to do studies to see if the heart is normal or if it is working harder, if there are rhythm abnormalities." One approach, he said, is to do an EKG test while exercising. The doctor can also put the individual in a cardiac rehabilitation program for one day to monitor his heart. For complaints that are infrequent, it is possible to use an Event Recorder - the patient pushes a button when his or her heart beats fast and it is recorded and transmitted over the phone, or it is documented and transmitted later.

Dr. Cantwell also suggested that the physician can examine the heart to make sure it is not enlarged, that there is no heart murmur or other abnormalities. If there is any concern about symptoms or history, the patient or patient's parent can request a referral to a cardiologist. Unfortunately direct tests for small vessel disease would require complex catheterization, an invasive procedure not typically done on a child. If small vessel disease is detected, medical treatment -- for example, vasodilators like nitroglycerin -- might be recommended.

Dr. Dragovic pointed out, meanwhile, that there are five million children now using Ritalin or similar drugs in North America. While a few deaths may not be significant when talking about millions, they are 100% significant to their families. Saying that there would be no side effects from a drug "is as ridiculous as stating the earth is flat."

Research on the Safety of Ritalin

The claim by Dr. Rosenberg and others that the cardiac side effects of Ritalin are not significant has never been verified in any long-term studies, but only in short and 1-to-3 year studies.

One such study on the safety of both Ritalin and the combination of Ritalin with TCA is the study by Findling in 1996 on the use of Ritalin and TCA medications together and separately. While using only 22.5 mg of Ritalin alone, one of the 11 subjects, an adult, had a highly significant rise of 20 points in diastolic (the lower number) blood pressure. Depending on the original level, his blood pressure could have entered the "stroke zone." What would long term un-monitored use do to such a patient?

Findling concluded, however, that using these two medications together is safe, and said nothing in his abstract about the safety of Ritalin alone, even though it was clearly unsafe for that one person - and he was 10% of the sample.

Multiple studies since 1977 have shown that Ritalin affects the small blood vessels of the heart. Henderson & Fischer (1995) determined that lesions in the heart muscle seen in a patient on Ritalin could be caused dependably in rats and mice by administration of Ritalin. Dr. John Cantwell explained the connection -- when the small vessels cannot deliver appropriate amounts of oxygen to the myocardium (heart muscle cells), then those cells die. This forms the lesions that could be seen under the electron microscope. This effect is not reversible, according to the Henderson & Fischer study.

Apparently, moreover, not all children are equally affected. A study by Brown and Sexson (1989) concludes that "Because of the unexpected increase in diastolic blood pressure, careful monitoring of black adolescents who are receiving methylphenidate is recommended." This follows Brown's earlier study in 1984 which concluded that while the authors agreed that "cardiovascular functioning did not significantly increase as a function of methylphenidate" yet they caution that "due to the large intraindividual variability in cardiovascular response, careful monitoring of each patient's response is recommended." Translated, this means that while the effects are not significant averaged together, for some individual children they are indeed serious.

Update as of 2011:
While several articles have been added about stimulant drugs, heart disease, and sudden death, there still does not appear to be any specific discussion of the connection between stimulants and small vessell disease in the American Heart Association website.
The American Heart Association's scientific advisors have been asked to comment about these studies, as well as whether they may know of any ongoing studies about unusual risk to African-American children. Jim Kiser, on behalf of their staff scientists, responded that the AHA has not yet taken a good look at the Brown and Sexson 1989 study, and therefore has no opinion on it. The scientists will be provided the study for future analysis. Kiser says that the AHA does fund research studies, and he agreed to pass on to the AHA scientific staff the specific request to consider funding scientific studies relating to the safety of Ritalin use in African-American children.

The American Heart Association does not discuss small vessel disease in connection with Ritalin, on their website. In fact, until recently they specified on their site that children on Ritalin do not need to be monitored. After our communication, it was observed that the link to the page containing the specification was removed from its prominent place on the AHA Home Page, and later was removed altogether from the organization's search and site map.

While the stimulant drugs Ritalin, Adderall, etc. are ignored by the American Heart Association, however, they have several interesting articles on the connection of heart disease and the other stimulant drugs caffeine and cocaine: [The original links used in this article are no longer active, but following are updated search results of their website]

Following are more articles on the risk of heart disease and stroke. Note that chronic high blood pressure is a major factor, yet the chronic elevated blood pressure in children or adults taking Ritalin - especially Black children - is not mentioned:
  • Search results on risks of heart disease for African-Americans ... all risk factors discussed except Ritalin use.

  • Stroke Risk Factors
    • "High blood pressure - High blood pressure is defined in an adult as a systolic pressure of 140 mm Hg or higher and/or a diastolic pressure of 90 mm Hg or higher for an extended time. It's the most important risk factor for stroke. "
    • "Cigarette smoking - In recent years studies have shown cigarette smoking to be an important risk factor for stroke. The nicotine and carbon monoxide in cigarette smoke damage the cardiovascular system in many ways. Using birth control pills and smoking cigarettes greatly increases stroke risk." (How many young people taking Ritalin long term also smoke and / or use birth control? Are they adequately warned not to?)
    • "Diabetes mellitus - Diabetes is an independent risk factor for stroke and is strongly correlated with high blood pressure. While diabetes is treatable, having it still increases a person's risk of stroke. People with diabetes often also have high cholesterol and are overweight, increasing their risk even more." (Are parents of children with diabetes and ADHD warned of this connection?)
    • "Excessive alcohol intake - Excessive drinking (an average of more than one drink per day for women and more than two drinks per day for men) and binge drinking can lead to stroke. It can also raise blood pressure, contribute to obesity, high triglycerides, cancer and other diseases, and cause heart failure." (Are our children with ADHD adequately warned about this as they enter their late teens?)
    • "Certain kinds of drug abuse - Intravenous drug abuse carries a high risk of stroke from a cerebral embolism . Cocaine use has been closely related to strokes, heart attacks and a variety of other cardiovascular complications. Some of them have been fatal even in first-time cocaine users." (Are our children with ADHD adequately warned that they may be even more at risk than their friends?)

For the Future

"And remember ... first do no harm."
Dr. Ljubisa Dragovic,
Medical Examiner
2000
Dr. Dragovic stressed (in our conversation held in 2000) that 5 million children in North America were being given Ritalin or similar drugs regularly. It is also known through Drug Enforcement Administration (DEA) reports that there has been a 9-fold increase in the abuse of Ritalin in the 10 years from 1990 to 2000, mostly by young people who crush it for snorting or injecting. What we are seeing in this area, he said, is "astonishing and brings up an awareness that there is an ocean-sized problem out there that needs to be looked at very carefully by multidisciplinary teams for careful reassessment of the use of this drug."

"In a balanced view," he continued, "one cannot neglect the reports and one cannot neglect the experimental studies that have shown clearly that there is a valid concern. If there is one death, we don't have to wait for 100,000 people to die before we conclude that it is dangerous. We have to have what we call intelligence."

"It is very logical that the more [Ritalin] people use, the greater are the chances for the development of these vessel changes and the greater the chances to experience serious health problems relative to the cardiovascular system and drug dependency."

Although Matthew and his family were healthy with no heart disease or other risk factors, and thus no way to predict this outcome, he did warn that in some cases there are risk factors to consider. Children with diabetes, for example, have a propensity to develop coronary problems. This could possibly mean that children with diabetes are more at risk than the general population.

Now that older children as well as adults are using Ritalin, there is an added problem of alcohol use. Dr. Dragovic discussed the combination of cocaine and alcohol, in which a chemical called cocaethylene is formed in the liver. This prolongs the half-life of cocaine, which is the length of time for half the cocaine to leave the body. The alcohol thus potentiates [makes stronger] the effect of the cocaine, causing possible overdose situations. Because both cocaine and Ritalin are stimulant drugs, while alcohol is a CNS (central nervous system) depressant, there may be the same situation with Ritalin, but he had not seen a case yet. (Remember, Medical Examiners only see cases that result in death.) There have been deaths, however, reported by Markowitz (1999) in which the combination of alcohol and Ritalin resulted in a chemical called ethylphenidate which was found in their blood and liver samples. A study by Markowitz (2000) suggests that even in non-overdose situations, "the metabolite ethylphenidate may contribute to drug effects." If your child on Ritalin insists on using alcohol, discuss with his physician whether continuing the Ritalin is wise.

Dr. Dragovic is concerned because there has been a substantial number of cardiovascular problems being reported about Ritalin. He is also aware of the cardiovascular effects of similar drugs. He appealed to those who are prescribing such medication, to weigh the risks and benefits, saying "My message will be that clinicians continue to treat their patients as individuals, not as diseases. Re-focus and look for potential side effects. And remember ... first do no harm."


References

  1. Cardiovascular responses of hyperactive children to methylphenidate. Ballard JE et al., JAMA 1976 Dec 20;236(25):2870-4

  2. A controlled trial of methylphenidate in black adolescents. Attentional, behavioral, and physiological effects. Brown RT, Sexson SB, Clin Pediatr (Phila) 1988 Feb;27(2):74-81

  3. Effects of methylphenidate on cardiovascular responses in attention deficit hyperactivity disordered adolescents. Brown RT, Sexson SB, J Adolesc Health Care 1989 May;10(3):179-83

  4. Attention deficit disorder and the effect of methylphenidate on attention, behavioral, and cardiovascular functioning. Brown RT, Wynne ME, Slimmer LW, J Clin Psychiatry 1984 Nov;45(11):473-6

  5. Methylphenidate's effects on paired-associate learning and event-related potentials of young adults. Brumaghim JT, Klorman R, Psychophysiology 1998 Jan;35(1):73-85,

  6. Effect of methylphenidate on young adult's vigilance and event-related potentials. Coons HW et al, Electroencephalogr Clin Neurophysiol 1981 Apr;51(4):373-87

  7. Open-label treatment of comorbid depression and attentional disorders with co-administration of serotonin reuptake inhibitors and psychostimulants in children, adolescents, and adults: a case series. Findling RL, J Child Adolesc Psychopharmacol 1996 Fall;6(3):165-75

  8. Atrioventricular nodal re-entrant tachycardia associated with stimulant treatment. Gracious BL, Journal of Child Adolescent Psychopharmacology 1999;9(2):125-8

  9. Effects of methylphenidate (Ritalin) on mammalian myocardial ultrastructure. Henderson TA, Fischer VW, Am J Cardiovasc Pathol 1995;5(1):68-78

  10. Biphasic inotropic effects of methamphetamine and methylphenidate on ferret papillary muscles. Ishiguro Y, Morgan JP, J Cardiovasc Pharmacol 1997 Dec;30(6):744-9

  11. Attention deficit disorder and methylphenidate: a multi-step analysis of dose-response effects on children's cardiovascular functioning. Kelly KL, Rapport MD, DuPaul GJ, Int Clin Psychopharmacol 1988 Apr;3(2):167-81

  12. Mechanisms of cardiac and vascular responses to cocaine. Knuepfer MM, Branch CA, Fischer VW, NIDA Res Monogr 1991;108:55-73

  13. Cocaine-induced myocardial ultrastructural alterations and cardiac output responses in rats. Knuepfer MM, Branch CA, Gan Q, Fischer VW, Exp Mol Pathol 1993 Oct;59(2):155-68

  14. Methylphenidate and nortriptyline in the treatment of poststroke depression: a retrospective comparison. Lazarus LW, Moberg PJ, Langsley PR, Lingam VR, Arch Phys Med Rehabil 1994 Apr;75(4):403-6

  15. Effects of background anger, provocation, and methylphenidate on emotional arousal and aggressive responding in attention-deficit hyperactivity disordered boys with and without concurrent aggressiveness. Pelham WE, J Abnorm Child Psychol 1991 Aug;19(4):407-26

  16. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Volkow ND et al, Life Sci 1999;65(1):PL7-12

  17. Methylphenidate decreases regional cerebral blood flow in normal human subjects. Wang GJ, et al., Life Sci 1994;54(9):PL143-6

  18. Absence of cardiovascular adverse effects of sertraline in children and adolescents. Wilens TE, Biederman J et al, J Am Acad Child Adolesc Psychiatry 1999 May;38(5):573-7
Home ||| Research Menu Page |||