DC Child Accident & Safety Blog

Is this a case of more is less? Some pediatric hospital patients, especially those with unusual disorders, are given so many drugs and therapeutic agents that their treatment is raising questions of unacceptable risks.

Readers of a report published in the Archives of Pediatrics and Adolescent Medicine are certainly invited to draw that conclusion.

The problem isn’t necessarily the number or nature of the drugs, but the fact that many facilities lack an established, scientific protocol for child safety in administering them.

Like adults, children often are given prescription drugs for “off-label” uses -- that is, to treat a problem other than the one for which the medication was developed. And also like adults, children sometimes are victims of medication errors. The groundswell of legislation in the last decade to improve the labeling and administration of medication to children is testimony to the need to separate the the determination of dosing for adults and for children.

“To advance this agenda,” the study authors wrote, “we need to refine our knowledge of the overall patterns of pediatric inpatient drug and therapeutic agent use, including what drugs and therapeutic agents are used most commonly, the number of different drugs and therapeutic agents that hospitalized children receive, and potential differences in drug and therapeutic agent exposures across different types of hospitals.”

The researchers surveyed academic medical centers, community-based hospitals and large systems of multiple hospitals. They studied more than 700,000 pediatric patients across 411 different hospitals.

The drugs most commonly given were acetaminophen (Tylenol), albuterol (for relief of respiratory issues such as asthma) and antibiotics.

On the first day of their stay in a children’s hospital, patients younger than 1 received 11 drugs and older patients received 13. In a general hospital, kids younger than 1 got eight drugs and those older got 12. By day seven of hospitalization in a children’s hospital, the youngest babies had received 29 drugs, and the older childern had gotten 35. General hospital figures were 22 and 28 respectively. The odder the illness, the more likely it would attract greater drug exposure.

That’s a lot of medicine for a developing body to metabolize, and while that is neither positive or negative, the sheer volume bears scrutiny. The authors suggest that:

• ranking the drugs and frequency of their use for hospitalized children can suggest priorities for further research;


• the use of multiple drugs raises concern for patient safety because such “polypharmacy” (multiple drugs) in adults has shown adverse effects;


• establishing a database of use offers opportunities to compare effectiveness and study safety.

The point is to learn if pediatric patients receive too many drugs, too few and/or in the proper combination.

Many adolescents diagnosed with depression and attention deficity-hyperactivity disorder (ADHD) are prescribed both methylphenidate (Ritalin) and fluoxetine (Prozac). A study on rats given the two drugs might give humans pause.

As reported in the Los Angeles Times, the study showed that adult rats who got that drug combination as pups were more likely than those with no early exposure to psychotropic drugs to choose highly sugared water over plain water, and to linger in a compartment where they had gotten a dose of cocaine, which suggests they were hoping for more. Those are disturbing signs of developing addiction.

"Taking Ritalin and Prozac together during adolescence appears to set in motion subtle changes in brain function that, in adulthood, makes an individual more sensitive to reward as well as to stress, and more likely to exhibit the pessimism and hopelessness seen in depression," was how The Times summarized the study published in the Journal of Neuroscience.

The study's authors wrote, "combining methyphenidate and fluoxetine early in life may lead to lifelong behavioral and chemical abnormalities." They said the drugs--one a stimulant, one an anti-depressant--in combination appeared to act on the brain in much the same way as does cocaine.

Those drugs affect production of certain proteins in the brain's reward circuitry. If it's disrupted during adolescence, the adult later might struggle with the ability to regulate mood and to moderate reward-seeking behavior such as eating or sexual activity.

Baby rats who got only Prozac seemed more sensitive to rewards as adults, but were also more resilient to stress than those who didn't. The rats who got only Ritalin demonstrated less inclination toward sugar water, as well as a "significant aversion to cocaine" as adults--a sign that treating ADHD might thwart drug abuse later. But they also showed greater sensitivity to stress later on.

A rat is not a kid, and a trial subject rat is not depressed or afflicted with ADHD. So no straight line can be drawn between the study results and a child with these disorders who takes these drugs. If the study is notable, it is too preliminary for parents to withhold these drugs if they've been prescribed for their children with mood and behavioral problems. It's never too early, however, for a conversation with your doctor about the appropriate use of prescription drugs, and alternative treatments.

An FDA advisory panel has voted 21-0 in favor of adding dosing instructions to Children’s Tylenol and other products containing acetaminophen for children between 6 months and 2 years.

Currently, the liquid formulas do not contain dosing information for children under 2. Panel members said the lack of information can lead parents to give their kids an incorrect dose of the drug.

Acetaminophen-related overdoses are most common among children younger than 2, and have increased over the past decade, according to FDA data. While safe when used as directed, acetaminophen has long been subject to warning labels because it can cause serious and even fatal liver damage when overused.

Dosing errors with children’s acetaminophen products accounted for 7,500 of the 270,165 emergencies reported to poison centers last year, according to the American Association of Poison Control Centers.

Overdoses can be caused by parents not reading the label, misinterpreting the dosing instructions or using a spoon or other container instead of the cup included with the product.

The panel also voted unanimously that medicines should include dosing information based on children’s weight, and to limit cup measurements to milliliters, because having both teaspoon and milliliter markings can cause confusion.

The proposed changes have been discussed at FDA meetings since the mid-1990s. FDA is not required to follow the recommendations of its advisory panels, though it often does.

Source: Associated Press

Nearly half the children treated as inpatients for psychotic and mood disorders are given atypical antipsychotics, a new single-center study reports. About 44% of these young patients with a variety of conditions, ranging from psychosis to various mood and anxiety disorders, were treated with either first- or second-generation versions of the drugs, according to the study, which was recently presented at the American Psychiatric Association meeting in Honolulu.

To determine the prevalence of antipsychotic use and associated clinical characteristics - and to compare current use with past use - the researchers looked at 3,851 inpatients ages 5 to 17 who were seen at their facility between January 2000 and June 2010 for various diagnoses, including psychosis, behavioral disorder, depression, post-traumatic stress disorder (PTSD) and anxiety.

They found that antipsychotics were prescribed for 44.3% of patients, and that a higher proportion of those scrips were written for children (ages 5 to 12) than adolescents (ages 13 to 17) - 51.7% versus 41.7%.

Atypical prescribing varied by diagnosis, with prescriptions written for:

• 76% of psychosis patients (including schizophrenia and bipolar disorder)

• 45% of behavioral patients (including ADHD, panic disorder, and social phobia)

• 24% of depression patients

• 46% of PTSD patients

• 31% of anxiety patients

• 20% of patients with other diagnoses

The study authors expected atypical use to be most common in people with psychotic systems, but were surprised to see such high use of atypicals in behavioral diagnoses. The likely explanation is that the study focused on inpatients, who may exhibit more severe behavioral issues than outpatients.

Atypical antipsychotics were also more likely to be prescribed to males, nonwhites and those with a longer length of stay. Surprisingly, the general use of atypicals decreased over the study period, from 47% between 2001 and 2003 to 43.5% between 2006 to 2010.

The study was limited because it was done at a single center and because it lacked follow-up after discharge, and the study authors called for further study and the need for comparison with other institutions.

Source: Medpage Today

Study reference: Stevens M, et al "Current prescribing practices: antipsychotic use in children and adolescents" APA 2011; Abstract 12-41

The Food and Drug Administration (FDA) says it continues to receive reports of methemoglobinemia, a serious and potentially fatal adverse effect, associated with benzocaine products both as a spray used during medical procedures to numb the mucous membranes of the mouth and throat, and benzocaine gels and liquids sold over-the-counter and used to relieve pain from a variety of conditions, such as teething, canker sores, and irritation of the mouth and gums.

Methemoglobinemia is a rare but serious condition in which the amount of oxygen carried through the blood stream is greatly reduced. In the most severe cases, methemoglobinemia can result in death. Patients who develop methemoglobinemia may experience signs and symptoms such as pale, gray or blue colored skin, lips, and nail beds; headache; lightheadedness; shortness of breath; fatigue; and rapid heart rate.

While methemoglobinemia has been reported with all strengths of benzocaine gels and liquids, most cases occurred in children aged two years or younger who were treated with benzocaine gel for teething. The signs and symptoms usually appear within minutes to hours of applying benzocaine and may occur with the first application of benzocaine or after additional use. The development of methemoglobinemia after treatment with benzocaine sprays may not be related to the amount applied. In many cases, methemoglobinemia was reported following the administration of a single benzocaine spray.

The FDA recommends that Benzocaine products not be used on children under 2 years except under the advice and supervision of a healthcare professional. It also recommends storing these products out of the reach of children.

Source: Food and Drug Administration

The Food and Drug Administration (FDA) has undertaken a review of recombinant human growth hormone (somatropin) after a French study determined that some kids who take it because they are abnormally short may be at a small increased risk of death.

The FDA does not recommend that patients stop taking recombinant human growth hormone before talking to their physicians, as it believes the benefit of the hormone still outweighs its potential risks. However, the FDA is now reviewing all available information on this potential risk and plans to issue new recommendations, if necessary, once the review is completed.

Meanwhile, healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program here.

Recombinant human growth hormone, a manufactured protein that is nearly identical to the main form of the naturally occurring human growth hormone, can stimulate tissue growth, protein, carbohydrate, lipid and mineral metabolism, and increases in height and weight.

In the U.S., it is used to treat children with short stature due to growth hormone deficiency (including idiopathic growth hormone deficiency), Turner syndrome, Noonan syndrome, Prader-Willi syndrome, short stature homeobox-containing gene (SHOX) deficiency, chronic renal insufficiency, and idiopathic short stature, as well as children small for gestational age. Recombinant human growth hormone is marketed under the following brand names: Genotropin, Humatrope, Norditropin, Nutropin, Nutropin AQ, Omnitrope, Saizen, and Tev-Tropin.

Source: Food and Drug Administration

Given the importance of correct dosing of over-the-counter pediatric medicines, you would think that the labeling on the package and the dosing information would be clear and understandable for parents. Unfortunately, a recent study published in the Journal of the American Medical Association (JAMA) says that is usually not the case, with potentially deadly results.

The study examined the directions and measuring devices in 200 non-prescription pediatric liquid medicines for allergy, cough and cold, pain and gastrointestinal problems, as well as some combination medicines, over one year ending Nov. 1, 2009. The sample represented 99% of over-the-counter liquid pediatric medicines sold in the United States.

Researchers found that 52 medicines did not include a measuring device, and that 146 of the other 148 had inconsistencies between the dosing directions and the devices, including missing or superfluous markings, unfamiliar units of measurement (for example, drams or cubic centimeters), or undefined or nonstandard abbreviations. More than 24% of the medications that did include measuring devices had missing markings, while 120 had superfluous markings. Meanwhile, 11 of the 200 medications used little-known units of measurement, such as drams and cc, for doses listed.

The Food and Drug Administration (FDA) published voluntary guidelines for labeling of dosing directions and measuring devices for over-the-counter liquid medicines in November 2009 and expects to see changes by next winter, according to the study’s lead author, Dr. Shonna Yin. At that time, Yin says, the study will be redone to determine if the voluntary guidelines work.

Source: The New York Times

You can view the JAMA abstract here.

Prescriptions of anti-psychotic drugs like Risperdal for pre-school kids have doubled in the last few years, according to a recent study from Columbia University. Now there are an estimated 500,000 children and adolescents receiving such drugs in the United States. Is it too much?

Only four in ten of the preschoolers who receive prescriptions for these powerful drugs have been given a proper mental health assessment, according to the Columbia study. That worries some experts. As one told the New York Times:

“There are too many children getting on too many of these drugs too soon.”

This quote was from Dr. Mark Olfson, professor of clinical psychiatry at Columbia and lead researcher in the new study, which was financed by the government.

Olfson and other researchers worry that the drugs can interfere with physical and mental development in young children. What many kids need is talk therapy, but it's cheaper and more convenient to medicate them, they say.

Read more in the Times' article here.

An article recently published in the Journal of American Medical Association documents findings that associate atypical antipsychotics to weight gain in children who are first-time users of the drugs. The study, headed by Dr. Christoph Correll in New York, includes 272 youths age 4 to 19 and is “the largest and most definitive to date to establish a link between the drugs and weight gain,” writes Jonathan Rockoff of the Wall Street Journal.

The JAMA study examined four top-selling atypical antipsychotics (powerful drugs prescribed to treat schizophrenia and bipolar disorder): Abilify, Risperdal, Seroquel and Zyprexa. Among them, Zyprexa was found to cause the most weight gain: 19 pounds in 11 weeks. It was also found to “significantly raise levels of blood sugar, cholesterol, insulin and triglycerides,” thereby increasing users’ risk of diabetes and heart problems. Patients taking other three medications had an average of 10 to 13 pounds of weight gain.

Dr. Correll, the lead author of the study, recommends using extra caution in prescribing these atypical antipsychotics to youths under the age of 18, and encourages psychiatrists to frequently monitor the weight and metabolic rate of those who are taking these drugs.

Thirty-nine million prescriptions were written for American children in 2008 for drugs like Adderall and Concerta to treat attention deficit hyperactive disorder (ADHD), but new research suggests the drugs have only short-term benefit and may pose more harm to children than good if given for more than two years.

In a report in the Washington Post by Shankar Vendatam, scientists involved in a large federal study of the drugs sharply disagreed with one another about what the public should be told about their study results. One psychologist in the group of researchers said that parents needed to know that careful comparisons of the children in the study showed definite advantages of the drug treatment only in the first twenty-four months of use, and that longer use resulted in stunted growth, with drug-treated children typically an inch shorter and six pounds lighter than non-drug treated peers after 36 months of treatment. Another psychiatrist who participated in the study said long-term benefits were real but hard to demonstrate statistically.

The study is called the Multimodal Treatment Study of Children With ADHD (MTA). When its initial results were first published in 1999, a clear advantage was seen for behavior improvement in children who had taken the ADHD drugs in the first fourteen months of the study, compared to children who received only talk therapy or no treatment at all, and those results ignited a huge wave of popularity for the ADHD drugs with pediatricians and parents. But as the researchers have continued to follow the same children over the years, the advantage of drug therapy, at least as measurable statistically, disappeared.

Statistics, of course, do not necessarily apply in any one individual case. The take-away for parents is to be careful about any long-term use of drugs in their children and to continue to ask questions of doctors, and reach your own informed decisions about what to do.

Nearly every week, we hear more evidence that American children are over-medicated, especially with drugs that affect mood and behavior. Most recently, a panel of experts has denounced the overuse of Risperdal, a powerful antipsychotic drug, for attention deficit disorder. The drug has too many side effects, including potential development of permanent muscle twitching, to justify its use in mild conditions like ADD for which other options exist, according to the expert panel convened by the Food & Drug Administration to advise it on labeling changes.

What is behind the explosion in use of antipsychotic drugs in children (besides Risperdal, they include Zyprexa, Seroquel, Abilify and Geodon) is a drumbeat of support from leaders in child psychiatry. But that leadership is tainted by their ties to the drug industry -- ties that frequently don't get mentioned in public when these same doctors are lecturing their colleagues and advising worried parents. One leader, Dr. Joseph Biederman, a child psychiatrist at Harvard, was revealed by a Congressional investigation to have accepted $1.4 million from manufacturers of antipsychotic drugs that he did not disclose to his university. Another psychiatrist leader, Dr. Charles B. Nemeroff of Emory, had to step down as chair of psychiatry after it was revealed that much of his consulting pay from drug makers, which totaled over $2.8 million in seven years, had been hidden from his university.

Now another influential psychiatrist has been exposed for his secret ties to the drug industry. He is Dr. Frederick Goodwin, former chief of the National Institute of Mental Health, who hosted a popular show on National Public Radio, "The Infinite Mind." Senator Charles Grassley of Iowa released data to the New York Times showing that Dr. Goodwin received $1.3 million from drug manufacturers from 2000 to 2007 for giving marketing lectures to other doctors. The money was never mentioned on his radio show, and NPR now says the show has been canceled and all reruns will stop soon.

According to the Times' Gardiner Harris, on one day in 2005, Dr. Goodwin received $2,500 from GlaxoSmithKline to give a talk about its mood stabilizer drug Lamictal at a Ritz Carlton resort in Florida. On his radio show broadcast the same day, Dr. Goodwin said that children with bipolar disorder who did not get treatment could suffer brain damage (a controversial prognosis) but he reassured his listeners that mood stabilizer drugs were a safe and effective way to treat the problem.

Senator Grassley has sponsored legislation to require drug makers to post publicly all the payments they make to doctor consultants. That would help the public to know whether the recommendations they see from doctors for medicating their children are truly unbiased or should be taken with a grain of salt.

We have discussed concerns over the efficacy and safety of cough and cold medicines for very young children many times in the past.

Now, in reaction to these concerns, the FDA plans to take another look at the reasons why these cough and cold medications were approved for toddlers and infants in the first place. From the article:

In response to rising concerns that the products are ineffective and could be unsafe, the agency said it will revamp the criteria that have allowed the products to remain on drugstore shelves for the first time in decades.

"Modern science has advanced since, and this is an opportunity to apply modern science to evaluate these products,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

As the first step in that process, the agency will hold a special hearing Oct. 2 to begin to consider a series of questions, including: What types of studies should be done to evaluate the products? Should the products remain available without a prescription? How should the doses be determined? Should products that combine different ingredients remain available?

One problem that has led to preventable tragedies is that parents sometimes inadvertently overdose their children. A particular problem has been with concentrated Tylenol infant drops. Due to confusing instructions from pediatricians and to labeling that wasn't always clear, some parents have not realized that the infant drops contain much more of the active ingredient, acetaminophen, then regular children's Tylenol. An overdose of Tylenol or acetaminophen can cause liver poisoning which requires liver transplant. After years of complaints, the Tylenol manufacturer took the concentrated infant drops off the market in October 2007.

The FDA's new look promises to go beyond the infant drops issue and look at the appropriate place of cough and cold medicines in treatment of infants and toddlers.

On this blog, we have discussed concerns over the efficacy and safety of cough and cold medications for very young children and babies many times.

Today, the Medicine and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has removed these medications from the shelves. Most of them will be allowed back on the shelves after the addition of a warning label saying that they should not be used on children under 2. From the article:

Sara Coakley, spokesperson for the MHRA, told BBC News it was a precautionary measure and the medicines are not dangerous.

"There's nothing wrong with these medicines, it was the way that they had been given," she said.

There was no need to panic, said Coakley, they would not be on the shelves in the first place if they were inherently dangerous.

The alert concerns 12 active ingredients: brompheniramine, chlorphenamine, dextromethorphan, diphenhydramine, ephedrine, guaifenesin, ipecacuanha, phenylephrine, pholcodine, pseudoephedrine, oxymetazoline, and xylometazoline.

According to Times Online, at least 5 deaths of children under the age of two and more than 100 cases of serious adverse events have been linked to cough and cold medicines in Britain.

The danger occurs when a child is given too much of the cough medicine or has more than one at the same time. Small children are more at risk of overdose because of their smaller body size, said the MHRA.

The MHRA is encouraging parents to give their children simple remedies like honey and lemon.

For more information, see the older discussions linked at the beginning of this post.

Around 7,000 children per year have to go to the emergency room because of cold medicines.

The study was done by the Centers for Disease Control and Prevention. Points to note:

-two thirds of the cases involved children taking the medicines without proper adult supervision or direction;

-one-quarter of the cases involved parents giving children the proper, recommended dosages;

-this study follows other stories that might raise concern about cold medicines and very young children, such as the FDA warning against such medicines for toddlers, a lawsuit filed by the mother of a boy who died after taking common cold medicines, and a voluntary recall by Tylenol, Dimetapp and others.

Recently, many have raised questions about the efficacy and safety of common cough medicines for children, many of which include the ingredient dextromethorphan.

But now an easy substitute seems to have been found: honey. Specifically buckwheat honey, which a new study has found to be more significantly more effective than dextromethorphan in curing coughs in young children. The study examined and compared the effects of dextromethorphan, honey and no treatment at all in 105 children. Honey was more effective than no treatment, whereas dextromethorphan was not.

The effective dosages of honey were: half a teaspoon for children aged two to five, a full teaspoon for those aged six to eleven and two teaspoons for the twelve to eighteen age group.

A month after the FDA change in labeling guidelines for cough and cold medications for children and a voluntary recall of those products, the mother of a boy who died after taking cold medication is filing a lawsuit.

The baby, son of Dimitria Alvarez of Illinois, was four months old. He died after taking Infant Tylenol Cold Decongestant Plus Cough and Walgreen-brand Pediatric Drops-Cough Plus Cold, according to the mother. The commonality between these two drugs is that they contain dextromethorphan, which is found in many cough and cold medications, including many of those recalled.

For more information on the uses of dextromethorphan, see this page from Medline Plus.

The Food and Drug Administration plans to meet to discuss the efficacy of cough syrup and cold medications for children. This comes on the heels of a voluntary recall of more than a dozen brands of children’s cough and cold medications, including Dimetapp, Robitussin, Tylenol and many others.

The FDA has already ordered a change of label guidelines for the use of such medications on children two or younger. Doctors are pushing for an outright ban, and also for restrictions for children up through age six. No study has been done demonstrating the safety of these medications on children, and quite a few have been done showing that they are no more effective than placebos and that overdosing is a serious problem. Parents, believing cough syrup to be completely mild and harmless, run the risk of giving overdoses to toddlers and very small children.

For more information and commentary:
Why give children placebos?

Doctors discourage use of cough syrup

On Wednesday, the FDA (Food and Drug Administration) issued a statement saying that children under 2 should not be given over-the-counter cough and cold medicine unless it's because of specific instructions from a healthcare provider.

What is the reason for this public health advisory? The FDA does not say, confining itself to a vague assertion that cough and cold medications may cause "harm" to extremely young children.

However, the Baltimore City Health Department submitted a petition to the federal government asking for tighter regulation of marketing for such drugs on behalf of several Maryland physicians, pointing to studies suggesting that these drugs are neither effective nor safe in children under 2.

The CDC (Centers for Disease Control) also has some important information about the effects of such drugs on very young children. An interview of theirs with Dr. Adam Cohen, who investigated infant deaths to to cold and cough medicines, is a good resource for some general facts on this topic.