Tag Archives: ADHD

Children on Antipsychotics May Have Increased Weight Gain Risk

Children who exhibit severe defiant and disobedient behavior that are treated with antipsychotics may have an increased risk of gaining weight as well as developing insulin resistance and other related conditions, a new study suggests.

Although antipsychotics are primarily used to treat conditions like pediatric-onset schizophrenia, they are also commonly used off-label to treat ADHD (attention deficit/hyperactivity disorder) and disruptive behavior disorders.

For about 4 years, researchers examined 144 children between the ages of 6 and 18 who had disruptive behavior disorders. Around 56% of the kids had a primary diagnosis of ADHD with irritability and aggression that was “insufficiently responsive to prior therapy.” During this randomized clinical trial, the children were treated with antipsychotics for 12 weeks and received oral Abilify (aripiprazole), Zyprexa (olanzapine) or Risperdal (risperidone).

The results, published in JAMA Psychiatry, found that children who were treated with antipsychotics for the first time experienced clinically significant increases in body fat over the course of 12 weeks. Total body fat increased by 1.18% for children taking Risperdal, 1.66% for Abilify and 4.12% for those taking Zyprexa.

Reductions in insulin sensitivity — leading to an increase in blood sugar levels — were also observed during the study.

“Adverse changes in adiposity and insulin sensitivity were observed during 12 weeks of antipsychotic treatment in youths, with the greatest fat increases on olanzapine. Such changes, likely attributable to treatment, may be associated with risk for premature cardiometabolic morbidity and mortality,” researchers said.

Now We Know: Endocrine Disruptors Affect Grandchildren

How do you study the effects of a group of chemicals that surround us daily, affect us before our birth and cause a variety of damages?

Endocrine disruptors are so terribly hard to study because they are ubiquitous — BPAs in our plastic bottles and lining cans of food; glycol ethers in many paints and cleaning products; PVCs in children’s toys and plastic food containers are just a few examples.

We hear a lot about endocrine disruptors because the endocrine system, a network of hormones and glands, is complex and delicate. Interfering with it can cause infertility, cancers, immune and nervous system disturbances and more. In a pregnant woman’s body, an endocrine disruptor can affect the development of a fetus or later, a newborn through breastfeeding.

How Disruption Works

Disruption happens when an outside chemical mimics hormones and sends the wrong signal to the body. It can tell the pancreas to produce insulin when it’s not needed, or give the wrong message to a developing fetus, causing organ malformations. It can cause cancers.

But there is a unique group of people who were exposed to only one endocrine disruptor years before other endocrine disruptors were around. The chemical was DES (diethylstilbestrol), and it was the first synthetic estrogen. By studying the DES-exposed and their offspring group, scientists can see what a single endocrine disruptor can — and did — do. From this group’s experience, we are learning about the risks from all the other endocrine disruptors.

DES was given in massive doses (much higher than general exposure to PBAs, the insecticide DDT or PVCs) to an estimated 5 to 10 million pregnant women from the 1940s until 1971. That was the year that DES was proven to have caused a rare vaginal/cervical cancer in young women, the daughters of those pregnant women given DES.

Abnormalities & Health Problems

In time we learned that exposure to DES also caused abnormal development of fertility organs, cardiovascular effects in some of the daughters and sons, and many other known and suspected health issues such as cardiovascular disease, diabetes, high cholesterol and sexual orientation. For more complete information, and to learn if your mother/grandmother was given DES in pregnancy, see DES Action USA, our sister organization.

But what about the grandchildren? Scientists worried that the epigenetic changes might be passed on to future generations through altered genes. For years we have worried, and scientists have searched for proof, and we now have it: DES has been positively linked to ADHD in the grandchildren of those pregnant women.

You can read the study in JAMA Pediatrics, or, even better, listen to this podcast of the study by an editor from JAMA Pediatrics. The upshot: Mothers given DES have increased odds of a grandchild being diagnosed with ADHD by 36%.

An editorial about this study states: “If disorders like ADHD are epigenetic conditions… it would have powerful implications for where national research dollars should focus to find ways to reduce the incidence of ADHD and other mental disorders. Discoveries about epigenetic associations as potential biomarkers of both illness and etiology that are related to common environmental exposures could hold promise to lead directly to renewed and targeted intervention to prevent ADHD and other illnesses from occurring. This may be the most exciting direction open to the field.”

A cure for ADHD? Unlikely. A way of avoiding it happening? Very possible now.

DES Exposure Boosts ADHD Risk in Grandchildren

Exposure to the synthetic estrogen called DES (diethylstilbestrol) during pregnancy may lead to neurodevelopmental disorders, such as ADHD (Attention Deficit Hyperactivity Disorder), across several generations, according to a study published in JAMA Pediatrics.

DES — which contains potent endocrine-disrupting chemicals — was given to many pregnant women between 1938 and 1971 to prevent pregnancy complications. Between 5 and 10 million pregnant women received the medication. The FDA then stated that DES was contraindicated for pregnancy. Studies later found that the medication was actually harmful and had few benefits.

In the new study, researchers wanted to explore whether there was an increased risk in the third generation (grandchildren) having ADHD when the first generation (grandmothers) was exposed to DES during pregnancy.

Researchers pulled data from the Nurses’ Health Study II (NHS II) and identified more than 116,000 registered nurses between the ages of 25 and 40 who enrolled in the study in 1989. More than 47,000 women — 861 (1.8%) of whom were exposed to DES while pregnant and 46,679 (98.2%) who were not — were included in the study.

Participants reported information through a questionnaire regarding their health, exposure to DES during pregnancy and ADHD diagnosis. All of the women who participated in this study were born during a time when DES was administered.

The results showed that the 47,540 grandmothers had more than 106,000 grandchildren, 5.3% (5,587) of whom were diagnosed with ADHD. The grandmothers of 137 grandchildren with ADHD (2.5%) were exposed to DES while pregnant with their daughters.

Overall, the study found “significantly elevated odds for attention-deficit/hyperactivity disorder in the grandchildren (third generation) of users of [DES], a potent endocrine disruptor.”

Rx Drug Use Among Adolescents Drops

A new study published in JAMA has found that prescription drug use among adolescents has dropped. The use of antibiotics, antihistamines and upper respiratory combination medications saw the biggest decline.

Researchers identified and examined 38,277 adolescents, aged 10 to 19 years, who participated from 1999-2014 in the National Health and Nutrition Examination Survey (NHANES), a survey that is conducted every 2 years.

From 1999-2014, children were interviewed face-to-face at home. During the interviews, they were asked whether they had taken any prescription medications in the past 30 days. If a child answered “yes,” then the interviewer would record the names of up to 20 prescription medications reportedly taken in the last 30 days.

The results of this observational study found that the use of any prescription medication by adolescents declined over time, going from 24.6% in 1999-2002 to 21.9% in 2011-2014.

Although there was an overall decrease in the use of any medication from 1999-2014, the use of asthma medication, ADHD (attention-deficit/hyperactivity disorder) medication and contraceptives increased among certain age groups.

Overprescribing: Do You Really Need to Take That Med?

Do you take 4 pills a day? If so, you’re like most Americans. Yet what are we taking all these pills for, and are they improving our lives?

The overuse of prescription drugs has become a serious problem in the US. We hear about this most in the context of opioids — narcotic painkillers whose widespread use and abuse has become a national crisis.

The overuse of antibiotics has also become the focus of an intensive campaign to steer doctors and patients to more judicious use.

The soaring use of prescription drugs has been driven by several factors: A plethora of new drugs coming to the market; a culture that has come to expect a “pill for every ill”; aggressive marketing to both doctors and consumers by the pharmaceutical industry; and treating some “pre-”diseases with pills rather than with lifestyle changes.

Between 1997 and 2016, the number of prescriptions filled in the US increased 85% — from 2.4 billion to 4.5 billion — even though the population increased by just 21%. Nearly half (49%) of adults take at least 1 prescription drug, 23% take 3 or more and about 12% take 5 or more, according to the latest data from the CDC (Centers for Disease Control and Prevention). One in 10 adults takes 10 or more drugs, and the average adult takes 4 prescription medications, according to a Consumer Reports survey of 1,947 adults conducted in April.

What can you do to make sure you’re not getting a drug you don’t need and to avoid harm?

Ten “secret shoppers” were sent to 45 drugstores across the US in a recent Consumer Reports investigative study. The shoppers were testing how well pharmacists identified potential problems with drugs.

Of course, it’s your doctor who should be your main consultant on the medicines you take. But bring a big measure of skepticism to your doctor visits: The evidence is now clear that they can be a part of the problem.

Based on the secret shoppers’ findings and more than a decade of Consumer Reports’ grant-funded Best Buy Drugs program, we have compiled a list of drugs that you should use special caution with when prescribed by your healthcare provider.

(For more detailed information, check out Consumer Reports’ September 2017 cover story and the physician-led Choosing Wisely program.

Abilify and Seroquel for Dementia or ADHD

These powerful antipsychotics have potent sedative effects and can be downright dangerous. Studies over the last decade show they have been overprescribed in general and particularly for elderly people with dementia.

The FDA and other healthcare and physician organizations now advise against their use entirely in elderly people. Multiple studies over many years have found an increased risk of death in elderly people prescribed these drugs.

Abilify (aripiprazole) and Seroquel (quetiapine) are also overprescribed to treat children and adults with attention-deficit/hyperactivity disorder (ADHD). The two drugs are not even approved for this condition. Their use to treat ADHD is not advisable unless a person is diagnosed with other psychiatric conditions, such as bipolar disorder. And even then, caution is warranted. Behavioral therapy is a better initial treatment for ADHD.

Advil, Aleve, Celebrex and Any Opioid for Back and/or Joint Pain

The non-steroidal anti-inflammatory drugs (NSAIDs) Advil (ibuprofen), Aleve (naproxen) and Celebrex (celecoxib) are commonly prescribed to treat back and joint pain (and headaches, of course). Short-term use — up to 10 days — is fine at the lowest dose that helps.

But long-term use — which is all too common — is ill-advised because all these drugs can cause bleeding in the intestines and stomach, and increase the risk of heart attack and stroke (especially at higher doses).

Opioids should simply never be a first-line treatment for either chronic back pain or garden-variety periodic back pain (“I threw my back out” kind of pain). The risks are too high. The side effects include drowsiness, sedation, nausea, vomiting, constipation, addiction and overdose. Instead, try yoga, swimming, gentle stretches, tai chi, massage, physical therapy, acupuncture or heat.

For intense pain flare-ups (pain in the range of 8 to 10 on a 10-point scale), an opioid can be useful, but it should be prescribed at the lowest dose that’s effective and for the shortest time possible, like a day or 2. And never more than a week to 10 days.

Celexa, Cymbalta, Lexapro and Prozac for Mild Depression

Antidepressants are overprescribed for people who have mild or so-called “situational” depression — that is, depression triggered by a life event such as a death in the family, job loss, divorce or breakup, accident, trauma or diagnosis with a serious health condition.

You don’t need a pill if these life events befall you. Social support, time and psychotherapy or counseling almost always help. Also, be sure to exercise and perhaps try meditation and/or yoga. For the vast majority of people who have situational depression, the symptoms lift within a few weeks to a couple months.

Nexium, Prevacid and Prilosec for Heartburn

These drugs, called proton-pump inhibitors (PPIs), reduce stomach acid. They were designed to treat a condition called gastroesophageal reflux disease (GERD). But they are greatly overprescribed for common, uncomplicated heartburn, which most of the time can be just as effectively treated with over-the-counter (OTC) products such as Maalox, Pepcid AC, Tums or Zantac 75.

The problem with taking PPIs is that they carry serious risks — a few of which were not fully appreciated until a few years ago. These include a reduction in the body’s ability to absorb certain nutrients and medications, along with an increased risk of gastrointestinal and other infections.

Instead, as a first-line treatment, eat smaller meals, don’t lie down soon after eating, lose excess weight, and avoid acidic or greasy meals that trigger heartburn.

If heartburn occurs twice weekly or more for 4 weeks or longer despite the above diet and lifestyle changes, then you might have damaged your esophagus. Check with your doctor, and if GERD is diagnosed, it would be appropriate to take a PPI for a few months while your esophagus heals.

Ambien, Belsomra and Lunesta for Insomnia

These strong sleeping pills are way overprescribed for people who have insomnia triggered by a life event, as well as for people who have chronic insomnia.

If you find yourself in the first group, try an OTC sleep aid containing an antihistamine, but not for longer than a few days. People with chronic insomnia are not helped in the long term by taking these medicines, recent evidence shows. Instead, try cognitive behavioral therapy (CBT), where a provider teaches you good sleep habits and suggests ways to change your behavior and nighttime habits.

Prescription medicines have significant side effects and risks, including dizziness, next-day drowsiness, impaired driving, dependence, and worsened sleeplessness when you try to stop.

AndroGel, Axiron, Androderm and Aveed for Low Testosterone

Low testosterone (“low T”) is a controversial diagnosis. If you get such a diagnosis and your doctor advises you to take any of these medicines, get a second opinion.

A small percentage of men (usually in their 50s, 60s and 70s) have “low T,” but the manufacturers of these products have sought to create a condition that is not firmly established in medical literature — one marked by low energy and low sex drive due to “low testosterone.”

Don’t buy into it. The drugs can cause blood clots in the legs, sleep apnea, an enlarged prostate and possibly an increased risk of heart attack or stroke.

Instead, talk to your doctor about treating common underlying conditions that can decrease testosterone level, such as diabetes, obesity and aging. Also discuss non-drug ways to boost energy and vitality by exercising, getting enough sleep and couples therapy with your partner.

Actonel, Boniva and Fosamax to Treat Osteopenia (Low Bone Density)

These drugs, called bisphosphonates, are widely prescribed to treat a condition dubbed “pre-osteoporosis.” But there’s scientific controversy about the prevalence and impact of mildly or marginally low bone density, and whether it warrants treatment with these strong medicines.

All have side effects and carry risks, which include diarrhea, nausea, vomiting, heartburn, esophageal irritation and bone, joint or muscle pain. Long-term use has also been linked to an increased risk of fractures of the femur (thigh bone).

Before considering one of these medicines, walk more, quit smoking and try eating more foods high in calcium and vitamin D. If bone density tests show you have full-blown osteoporosis, you should consider one of these medicines. But use caution with long-term use.

Detrol and Oxytrol for “Overactive Bladder”

The sudden or frequent need to pee is frustrating and inconvenient. These medicines, called anticholinergics, are often prescribed even to people who have mild symptoms.

The drugs can cause constipation, blurred vision, dizziness and confusion. So before trying one, cut back on caffeine, soft drinks and alcohol, and watch your liquid intake overall. Also, try bladder training (slowly increasing the time between bathroom visits) and Kegel exercises — repeatedly tightening and relaxing the muscles that stop urine flow. These techniques have been proven effective.

If several weeks or months of non-drug strategies don’t provide enough relief, consider an anticholinergic.

Actos and Glucophage for “Pre-diabetes”

Pre-diabetes is a widely accepted condition (unlike “low T”), but there’s no consensus on how aggressively to treat it, or if people with it should take drugs. People with pre-diabetes have blood glucose (sugar) levels at the high end of normal.

Because these diabetes medicines have side effects and carry risks — including dizziness, fatigue, muscle pain and, in rare cases, the dangerous buildup of lactic acid and a vitamin B12 deficiency — talk to your doctor about non-drug options first, such as exercise, a diet rich in unprocessed and non-starchy foods, and weight loss.

If you develop type 2 diabetes, however, you should consider a diabetes drug.

Drugs to treat Pre-hypertension

Like pre-diabetes, pre-hypertension is an accepted condition that warrants monitoring. It’s defined as blood pressure at the high end of normal. But, also like pre-diabetes, there’s no consensus on when to treat it with drugs.

Many classes of medicines are used. They include ACE inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers and diuretics. All are effective at lowering blood pressure but have side effects. Diuretics can cause frequent urination, low potassium levels and erectile dysfunction. ACE inhibitors and ARBs can cause high potassium levels and reduced kidney function. Calcium channel blockers can cause dizziness, an abnormal heartbeat, flushing, headache, swollen gums and, less often, breathing problems.

Unless a patient has other conditions that make the case for starting a drug, non-drug options are a better initial treatment to bring blood pressure into the normal range. Most important among them: Quit smoking, cut back on sodium and alcohol, lose excess weight, and exercise.

Belviq, Contrave, Qsymia and Xenical for Obesity

These weight loss drgs have mixed effectiveness. They work for some people and not at all for others. For patients who are significantly overweight or have diabetes or heart disease, and have been unable to lose weight through exercise and diet, one of these medicines may be worth trying.

But the drugs should not be a first-line treatment for anyone who is just 10 to 20 pounds overweight and hasn’t yet really tried lifestyle and diet changes. All have side effects that are common and can be quite discomforting. Constipation, diarrhea, nausea and vomiting are common.

The drugs also carry rare but dangerous risks, including leaky heart valves with Belviq and liver damage with Xenical.

Americans are all too often pushed — or rushed — into taking drugs too soon. Sure, lifestyle changes can be hard. But they don’t have side effects and the risks are well defined and easily avoidable. And the payoff from adopting a much healthier diet or sticking to an exercise regimen often goes well beyond addressing the medical condition at hand and improves your overall physical and mental health.

Why an FDA Drug Safety Monitoring System Is Failing

The late 1990s and early 2000s saw a number of prescription drugs come to market that ended up causing grave harm. Most famous among these was the arthritis and pain drug Vioxx (rofecoxib).

Approved by the FDA in May 1999, Vioxx soon became a multibillion-dollar drug, with peak sales of $2.5 billion a year, and was prescribed to millions of people. By 2001, initial studies indicated that the drug might be putting people at higher risk for heart attacks and strokes.

Alarm bells went off and a high-profile, wide-scale probe followed. The problem was confirmed and in September 2004, Merck pulled the drug from the market. But not before it resulted in an estimated 88,000 to 140,000 people having heart attacks or strokes, and as many as 56,000 deaths, according to a 2005 report conducted by the FDA.

How could that have happened? The short answer is that the way drugs get approved — often based on just a handful of studies in a few thousand people — can’t pick up every possible adverse effect or safety problem of a new drug. Only wide use, in tens of thousands or even millions of people, over many years will reveal some problems.

the pharmaceutical industry, researchers and the FDA have long known this. But it’s cost prohibitive to test drugs on tens of thousands of people. So “the system” relies on monitoring drugs after they’re approved to see if problems crop up with “real world” use.

In the wake of Vioxx and several other high-profile cases of post-approval harm — sometimes years after approval — lawmakers in Congress asked a simple question: If we have to live with imperfect pre-approval detection of possible problems, why can’t we radically improve the way we monitor drugs after they enter the market?

Birth of the Sentinel System

Very good question. In 2007, Congress mandated that the FDA develop a computer-based system to track and analyze the safety of drugs after they hit the market — and do it pronto.

Following a year of debate and discussion, in May 2008, HHS (Department of Health and Human Services) and FDA launched something called the Sentinel Initiative. It was the brainchild of then-HHS secretary Mike Leavitt and Mark McClellan, then the FDA commissioner.

Leavitt, somewhat of a hi-tech geek, pledged “a national, integrated, electronic system for monitoring medical product safety.” Ultimately, he said, Sentinel would “help monitor medical products throughout their entire life cycle and thus better ensure the protection and promotion of public health.”

Leavitt also linked Sentinel to another George W. Bush administration initiative, the Nationwide Health Information Network (NHIN), built in part on electronic health records. The NIHN was going to “connect clinicians across the healthcare system and enable the sharing of data as necessary with public health agencies,” Leavitt said.

You have probably guessed where this is going. The NHIN never materialized — at all. It was thwarted by what became a chaotic, controversial and expensive ($20 billion) program to push doctors and hospitals to adopt electronic health records.

Little Impact from Sentinel?

As for Sentinel, it still exists. But it, too, has dashed hopes and suffered from a combination of bureaucratic inertia, technical obstacles and a lack of urgency.

I took part in launching Sentinel from 2007 to 2010 as a consumer representative to the project. At the time, I worked at Consumers Union/Consumer Reports and co-directed a project — which also still exists — called Consumer Reports Best Buy Drugs.

We continue to lack a robust, comprehensive and modernized computer-based system in the US to detect problems with drugs once they come on the market.

To make a long story short, initial enthusiasm for Sentinel waned over time. The history and a probing critique of Sentinel are well told in a recent piece from the health and medical site STAT.

The article alleges that Sentinel has had “little measurable impact” after 10 years and a cost of $207 million. The current budget is $20 million per year. Most experts STAT spoke to questioned “whether Sentinel can adequately identify risks involving drugs.”

To date, the article says, Sentinel has led to changes in the labels of only 2 medications out of several hundred that have been assessed. None were removed from the market. Drug labels guide doctors in prescribing drugs, warn of potential serious problems to watch for, and help both doctors and consumers discern possible side effects.

In a written response to my email query about the STAT article and their perspective on Sentinel, the FDA emphasized that looking at just label changes or drugs pulled from the market was not an accurate or comprehensive way to assess Sentinel.

They said Sentinel had “informed the issuance of 5 safety communications, including 2 safety label changes” but also provided “reassuring” evidence for dozens of other drugs.

In their words: “This leads FDA to not take any visible action because FDA has concluded that the prescribing information adequately describes the risks and benefits.”

Most notably, the agency said, a full-scale FDA analysis that included a Sentinel analysis assessed whether long-term use of stimulant drugs to treat ADHD (attention deficit/hyperactivity disorder) was associated with cardiomyopathy and heart failure. The analysis “provided important new safety information and a deeper understanding of these medical products” the agency stated in its response, but led to no regulatory action. In other words, the drugs were cleared.

Fair enough. It is important to be reassured that medicines taken by millions, and especially children, are safe.

Is Drug Safety Monitoring System Underutilized?

But then FDA’s response turned somewhat more disingenuous. For example, FDA claims that Sentinel has been “fully operational” for only 18 months. That’s technically true because the agency called the program a “pilot” and “mini-Sentinel” for 8 years.

FDA basically claims Sentinel was not ready for prime time, and that during those 8 years it was “developing infrastructure and methods.”

Since I was involved and followed the program I know that by year 5 or 6, FDA had significant capabilities under Sentinel and did not use the tools and network at their disposal to fully test things out.

The network is, in fact, impressive, and another reason to wonder why the yield of meaningful information is not yet more useful. Sentinel is one of the largest “distributed data” networks in the US today and possibly the world. According to Harvard Pilgrim Health Care, the nonprofit health insurer based in Wellesley, MA, that now manages the program under contract to FDA, Sentinel now encompasses:

  • 18 organizations, including many of the nation’s largest health insurers (Aetna, Anthem, Humana, Kaiser Permanente) and various disease registries
  • 88 hospitals and other inpatient facilities
  • Prescription drug data on some 200 million people, with the routine accrual of data on 48 million
  • 4 billion prescriptions
  • 4 billion doctor or lab visits and hospital stays
  • 42 million acute inpatient stays
  • 7.2 billion unique medical encounters

The thing is, it’s well known that several of the insurers in this network already had their own drug and medical product safety monitoring systems in the early to mid 2000s. Indeed, Kaiser Permanente’s system picked up a signal on Vioxx in 2001-2002 that helped trigger the wider probes.

Why has it taken so long then to get things together and generate information about hundreds of drugs — safety, side effects, effects on different populations, special considerations — for both doctors and consumers? That was the promise, and it was a worthy one.

FDA’s explanation to me: Capturing the right and accurate data — for example, on both inpatient hospitalizations and outpatient clinic visits, and on deaths inside and outside the healthcare system — is just plain hard.

Yes, it is. I concur. That was the challenge — to overcome the obstacles and make it happen in the interests of public health.

FDA Slow to Develop Sentinel and Get It Rolling

The FDA officials who corresponded with me wrote: “FDA is [now] exploring novel linkages to vital records data systems to inform these outcomes, which could improve Sentinel’s ability to connect the dots between monitored products and fatalities occurring outside of the healthcare system.”

That should have happened years ago.

The problems and slow development of Sentinel would perhaps create less rancor if it were not the second time the agency had failed to build an adequate drug safety alert system.

Sentinel was designed to complement and supplement a legacy drug safety monitoring system called FAERS (FDA Adverse Event Reporting System), a database that contains information on adverse event and medication error reports submitted to the FDA by doctors, nurses, pharmacists, hospitals, lawyers, manufacturers and consumers.

Reporting into the system is voluntary except for drug manufacturers; they must report problems. FAERS has some big weaknesses, which the agency acknowledges. For one, because reporting is voluntary, only an estimated 10% of adverse events are reported. Reports are also not validated and many don’t contain enough data to permit a full evaluation of a potential safety problem, such as whether there is a causal relationship between a drug and an event.

And while FAERS data is available to doctors and the public, it’s not easy to use and so is rarely consulted by either. But in fairness, FAERS has resulted in some important drug label changes over the years, and helped push a few bad drugs off the market.

The upshot of all this is that we continue to lack a robust, comprehensive and modernized computer-based system in the US to detect problems with drugs once they come on the market. That is a big gap. Arguably, it’s a gap that is more important than ever to fill as the new administration in Washington and new FDA chief, Scott Gottlieb, intend to accelerate the approval of drugs.

Sentinel is at the cutting edge of the big-data revolution, and, as a concept, still has tremendous value and promise. The initial vision was a good one. But the FDA now needs to move much faster to deploy Sentinel to quickly identify unsafe drugs and adverse effects that consumers must be informed about.

Quick Hits: FDA Approves New Antibiotic, ADHD Med, and Opioid Use in Depressed Patients

The FDA has approved Baxdela (delafloxacin), a fluoroquinolone antibiotic that is used to treat acute bacterial skin and skin structure infections (ABSSSI). The drug is available as a tablet or intravenous injection. Labeling for the drug includes a “black box” warning due to serious adverse and potentially irreversible reactions that have been associated with fluoroquinolones, such as tendinitis and tendon rupture, peripheral neuropathy and central nervous system effects. In trials, the most common adverse reactions in patients observed were nausea, diarrhea, headache, elevations of the enzyme transaminase, which can indicate liver damage, and vomiting. Posted June 19, 2017. Via Melinta Therapeutics.

A new once-daily treatment for attention deficit/hyperactivity disorder (ADHD) has won FDA approval. Mydayis, a stimulant for patients 13 years and older, contains the same active ingredients as Adderall (amphetamine/dextroamphetamine), but lasts for up to 16 hours compared to up to 6 for Adderall and 12 for Adderall XR. Adderall and Adderall XR are both available as a generic. Like other stimulant medications, such as methylphenidate (Ritalin, Concerta, Daytrana), Mydayis has a “black box” warning because it has a high chance for abuse and can cause physical and psychological dependence. Posted June 20, 2017. Via Shire.

Patients with low back pain who also suffer from depression are more likely to be given opioids that are prescribed at higher doses. This is problematic, since patients with depression are at a higher risk of misuse and overdose of opioids. Researchers examined data on opioid prescriptions from 2004-2009 and found that those with low back pain who also had depression were twice as likely to be prescribed an opioid than those without depression. And over a year, they typically got more than twice the usual dose, according to the study published in the journal Pain Reports. The authors noted more study is needed to determine the risks and benefits of prescribing such powerful painkillers to those who are depressed. Posted June 20, 2017. Via University of Rochester Medical Center.

Do Your Psychiatric Drugs Keep You Up at Night?

If you take a medication for a psychiatric condition, you may have experienced troubled sleep — insomnia, daytime sleepiness, or any other numbers of sleep-related disorders. I have treated patients with myriad sleep difficulties who take antidepressants, antipsychotics and even medications to treat attention deficit/hyperactivity disorder (ADHD).

While no one wants to experience a poor night of sleep, it’s important to recognize whether the sleep problem you are having is a result of a side effect of a drug (or drugs) you are taking, or something completely independent of medication. That is why if you are on psychiatric medication – or any drug for that matter – and you find yourself having difficulty catching some Zs, it’s important to talk to your primary doctor, who may change your medication or refer you to a sleep specialist for further evaluation. In many cases, the benefits of a drug may outweigh the sleep-deficit side effects. Your physician can work with you to minimize the impact of them.

However, it’s a good idea to know what some of the sleep-related side effects are that have been reported with different types of drugs which act upon the brain. Let’s start with antidepressants. The most commonly prescribed ones are known as SSRIs (selective serotonin reuptake inhibitors) and have names including Prozac (fluoxetine), Zoloft (sertraline), and Paxil (paroxetine). Complaints of both insomnia and daytime sleepiness have been reported in patients with depression on SSRIs. Prozac’s impact on sleep has been the most widely studied. Interestingly, it has been shown to have both a sedating and energizing effect depending on the individual. Prozac can also cause decreased sleep efficiency, awakenings during the night, and interrupted REM (rapid eye movement) sleep, an important period during the sleep cycle that allows a person to dream vividly.

Antidepressants and Vivid Dreams

Another class of antidepressants, SNRIs (serotonin norepinephrine reuptake inhibitors), are known to cause sleep problems similar to those in SSRIs, as well as vivid dreams. Common SNRIs are Effexor (venlafaxine), Pristiq (desvenlafaxine) and Cymbalta (duloxetine).

Treatment with Effexor has also been associated with a condition known as dyskinesia that is characterized by occasional movement of one’s limbs, repetitive and involuntary movements of the extremities – typically the legs – usually during or just before falling asleep. There have also been cases where these involuntary movements have been seen a week after a person stopped taking Effexor.

One antidepressant, Wellbutrin (bupropion), has been associated with insomnia. However, studies that have examined electrical activity of the brain in patients taking bupropion indicate the drug actually increases REM sleep time.

It’s important to recognize whether the sleep problem you are having is a result of a side effect of a drug (or drugs) you are taking, or something completely independent of medication.

Antipsychotics are usually prescribed for schizophrenia and other psychotic disorders, though they are also prescribed for bipolar disorder and to supplement antidepressants in the treatment of depression. One of the most popular antipsychotics, Seroquel (quetiapine), has been associated with faster sleep onset and longer overall sleep time. A typical antipsychotic, Clozaril (clozapine) has also been associated with improving sleep onset and sleep time.

RLS (restless legs syndrome) can ruin a good night’s sleep and antipsychotics and antidepressants have been known to lead to cause it. The strong urge that RLS causes to uncontrollably move one’s legs can make it hard to sleep, lead to sleeplessness, irritability and depressed mood. Remeron (mirtazapine), an older, atypical antidepressant, is most likely to cause RLS. A case study found that RLS appeared to be provoked in patients on a low-dose of Seroquel. Interestingly, some evidence has shown that Wellbutrin may actually help to alleviate RLS.

Lifestyle Changes May Help Curb Sleep-Related Side Effects

However, you might find relief from RLS through lifestyle changes and/or taking certain vitamins. For example, going to the bed at the same time every night and getting up at the same time each morning can help. Also, there are some indications that a lack of some vitamins and minerals, such as iron, folic acid, magnesium, and vitamin B, can contribute to RLS.

Not surprisingly, insomnia and delayed sleep onset are associated with stimulants such as Adderall and Ritalin (methylphenidate), that are used in the treatment of ADHD. However, the effect of Ritalin on sleep may depend on the amount of time a child has been on the drug and when the medication is given. There have also been reports of children having difficulty falling asleep as they are being weaned off the medication.

Sleep is an important part of staying healthy and feeling good. Again, if you feel you are experiencing sleep issues as a result of medication, speak to your doctor without delay. Sleep-related side effects due to drugs impact relatively few patients. And if it ends up your sleep problems are not drug-related, the good news is there are steps you can take to rectify the situation. Changes in sleep hygiene and even in your bedroom environment can provide some of the most effective improvements, as can making sure you are getting enough sleep in the first place. As we are in the middle of Sleep Awareness Week, I recommend visiting the National Sleep Foundation’s website for more helpful tips.

This piece is based on an article, Adverse Effects of Psychotropic Medications on Sleep, published in the journal Psychiatric Clinics of North America in 2016.

New Studies Find No Link Between Antidepressant Use in Pregnancy and Autism, ADHD Risk

The offspring of pregnant women who take an antidepressant are not at increased risk of developing autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD), according to a pair of new studies.

Researchers in the first study examined data on nearly 36,000 live births. In pregnancies where the mother was taking an antidepressant – either a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor – 2% of the offspring developed autism. While this percentage was higher when compared to mothers who didn’t take an antidepressant, when confounding factors were considered, there was no statistically significant difference between the 2 groups, researchers reported in JAMA.

“Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors,” the authors wrote.

Another study, also published in JAMA, examined 1.5 million births in Sweden and maternal antidepressant use. While maternal antidepressant use during the first trimester of pregnancy, compared to women who didn’t use an antidepressant, was associated with a small increased risk of preterm birth, there was no increased risk for low birth weight, autism or ADHD.

“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” the authors of the second study wrote.

Feeling Anxious? Depressed? Check Your Meds

If you find yourself feeling on edge for no apparent reason while taking a cold medicine or diuretic, you most likely wouldn’t connect the two. However, anxiety happens to be just one of many mood-altering symptoms that can be brought on by certain meds.

“Many medications, whether prescribed or found over the counter, can cause psychiatric symptoms,” says Shiyun Kim, PharmD, BCACP, BCPP, CDE, a clinical pharmacist and clinical assistant professor at the University of Illinois Hospital & Health Sciences System, and a spokesperson for the American Pharmacists Association.

She explains that a wide range of factors influence the way a drug affects each person, including things like metabolism, underlying illness, and interactions with other drugs. “Any variations that occur, such as with improper doses or individual reactions, can result in undesirable psychiatric symptoms,” though they are relatively uncommon.

If you feel that you may be suffering from these side effects, notify your providers immediately. “Keep in mind that some medications can be stopped abruptly, while others need to be tapered to prevent further adverse effects,” Dr. Kim emphasizes. “Your provider can make the best decision with you.”

Take note of the following medications that can have these kinds of effects, and read on to find out how to minimize the risks.

Oxycontin and Similar Pain Medications

“Most prescription pain medication, such as oxycodone (OxyContin) or hydrocodone, can cause drowsiness, which can make one feel ‘cloudy’ and lack motivation — and these symptoms closely mimic depression,” according to Bree Meinzer, PharmD, CTTS, a pharmacy practice resident at Ohio Northern University. Opioids can also lead to more severe symptoms like paranoia, hallucinations, psychosis and dementia, especially at high doses. Signs that you may have taken too much of an opioid include trouble breathing and unconsciousness. People with opioid dependence and those who suffer from HIV, liver or lung disease or suffer from depression may be more susceptible to these effects, according to the World Health Organization. If you are on a pain medication that makes you drowsy or “cloudy” and you do not like how it makes you feel, you should talk to your doctor about other ways to adequately manage your pain.

Lasix, Microzide and Other Diuretics

Medications that reduce fluid retention and swelling, including furosemide (Lasix) and hydrochlorothiazide (Microzide), increase urination. This can lead to dehydration, especially in the elderly, and can result in hallucinations and dizziness, says Dr. Meinzer. SGLT2 inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance), which are drugs used to treat diabetes, can also increase urination and cause dehydration. If you are taking these types of medication, be sure to drink plenty of water to stay sufficiently hydrated. The amount of water to drink should be discussed with your doctor and is dependent on your weight. “These medications should also be taken in the morning or early afternoon to avoid frequent urination at night,” which could disrupt sleep, she advises.

Ask your doctor to take a look at your current medication regimen to rule out potential drug-drug interactions that could cause psychiatric side effects.

Requip and Other Dopamine Agonists. Medications like ropinirole (Requip), often prescribed for restless leg syndrome and Parkinson’s disease, increase the brain chemical dopamine, which helps regulate mood and behavior. Too much dopamine can cause hallucinations, notes Dr. Meinzer, and more extreme potential side effects include confusion, mania, depression and impulse control disorders like compulsive gambling or eating. “There are other options for restless leg syndrome that don’t increase dopamine, though medications like ropinirole typically work best.” There are also different medications for Parkinson’s, though you and your doctor should carefully consider your particular treatment needs. If you experience these kinds of symptoms while taking this type of medication, it may be that your dose is too high.

Ritalin, Adderall and Other Stimulants

Drugs that are commonly used for the treatment of attention-deficit hyperactivity disorder (ADHD) include those sold under the brand names Ritalin and Adderall. Although these stimulant medications “help children and adolescents focus and stay on task, side effects include increased heart rate and insomnia, which can often cause anxiety and restlessness,” says Dr. Meinzer. Stimulants “excite the central nervous system and can disrupt normal communication between cells in the brain,” adds Dr. Kim. “This class of drugs may also cause bizarre behavior, agitation, mania, paranoia and nightmares.” Dr. Meinzer suggests talking to your healthcare provider if you feel extremely restless and anxious while taking this type of medication. Again, it is possible that your dose is simply too high.


Medications like prednisone, cortisone and methylprednisolone are often prescribed “to help respiratory symptoms and decrease inflammation with chronic diseases,” Dr Meinzer explains. They are typically only “used for a short term to help alleviate symptoms, but if you are on these medications for a long time, they can cause some unwanted side effects.” Use of these drugs for more than a few months can increase the chances of experiencing mania, anxiety, depression, paranoia and psychosis, which have mostly been reported by patients using high doses or abusing the medication, says Dr Kim. Though experts are unclear about the exact reasons for such side effects with these drugs, research suggests that it may have to do with the way steroids work in the area of the brain that influences memory and emotion. It is also possible that “high levels of steroids result in brain damage and cause cognitive dysfunction.”

Zarontin and Other Anticonvulsants

Medications such as ethosuximide (Zarontin), which are used to control seizures in people with epilepsy, can cause symptoms resembling depression. These drugs have also been found to increase suicidal thoughts and behavior. “If you start to experience these symptoms on an anticonvulsant, you should talk to your doctor about other regimens,” Dr. Meinzer recommends. “There are other medications in the same class that are less likely to cause this side effect,” though your doctor may want you to stay on the medication because it may be the one that is most effective for you. “Anticonvulsants are usually tricky to dose and may need lab monitoring to make sure they are in the proper range.”

Dr. Kim offers the following general tips to help prevent or deal with these side effects:

  • When you are prescribed a drug, ask your provider about potential side effects that are commonly noted and reported.
  • Ask your provider to take a look at your current medication regimen to rule out potential drug-drug interactions that could cause psychiatric side effects.
  • Withdrawal of some drugs can cause symptoms such as anxiety, agitation or depression. Therefore, call your doctor before stopping medications on your own.
  • When purchasing an over-the-counter (OTC) medication, take the time to read the instructions on the package. If anything is unclear, ask the pharmacist for guidance.

Episode 8: Informed Consent

Can a 7-year-old give informed consent regarding a prescription medicine? Su and Jonathan discuss this awkward question.

Su Robotti: Hi, I’m Suzanne Robotti, the founder of MedShadow, and our content manager is Jonathan Block We’re here today to talk to you about informed consent in children.

If you are at the doctor’s office, and your doctor is prescribing antibiotics for your 9-year-old, do you ask your 9-year-old for his or her opinion? Do you ask a 7-year-old if she wanted shots? I don’t know, but the American Academy of Pediatrics is suggesting that, yes, the child should have a role in informed consent.

Informed consent has a long history and a proud history. It’s a recognition by the medical establishment that the patient has a right, and even responsibility, to understand what medical procedure or medical care they are about to receive, and if the patient doesn’t want that care for any reason at all, that is the patient’s decision, not the doctor’s.

Children are different. Should they have a voice, Jonathan?

JB: I think that they should have a voice, but as far as the size of that voice, I think depends on a couple of situations. One is the age of the child. A lot of times you might get a 7-year-old, as what you said, if they wanted to get a shot, they’ll say no because it might hurt, but the benefits of getting a shot are obviously much better for the child. Where I could see informed consent coming into view, and I would support it, would be for adolescents or children that have gone through their lives, if they have had a major medical issue, they are more mature, they have a better understanding of what’s going on with them. And I think that when you’re of a certain age, maybe 12, 13, I think at that point you understand the benefits and risks of a certain medical procedure or medication, and that you should take a 12- or 13-year-old’s desires and opinions when making health decisions.

SR: Well the American Academy of Pediatrics came out with the statement that says children as young as 7 should have an opinion on their medical care in certain conditions, and my examples earlier were clearly exaggerated. The American Academy of Pediatrics does not suggest a 7-year-old be able to resist taking a tetanus shot. That’s really not a decision that they should get, a thumbs up or thumbs down, a vote on.

But, it did give as an example, medicine for ADHD, and it quoted a study that showed when parents and children were told together about the risks and benefits of ADHD medicine, the children showed as much comprehension as the parents in a quiz a few minutes later.

I’m going to be a wise guy here and say that that kid probably doesn’t need ADHD medicine in that case, but I’m being a wise guy. And that was an example where the AAP said, yes, the child should have a very significant vote there. Again, does that make sense to you?

JB: Yes, I think that in the situation that you just described, it is important to get, at least input, from the child. Just because a kid who’s 7 years old doesn’t mean that they’re completely absent from the conversation on their medical treatment. I think it’s important to have kids be informed as much as they can understand given their age. And I think it is important for them to understand, even at a young age, why the treatment is being given. And it also can have a longer effect in that if you started out with them understanding why certain medical decisions are made at an early age, it will likely them more likely to be better informed as they get older about health.

SR: Certainly they should understand the ins and the outs. There are a couple of cases where the medical community and, in most cases, the law agrees that the child can make decisions without any input from the parents with the parents not even knowing, and that generally speaking is, healthcare doesn’t do a sexual activity, anything having to do with contraception, sexually transmitted diseases, pregnancy. In most cases, medical communities say you can deal directly with the child without any parental involvement, and also in case of mental illness, or in substance abuse, the child definitely gets the say there.

JB: Well, I think it’s something, it’s also important to note that the American Association of Pediatricians said is that doctors themselves also play a role. Obviously if a kid is old enough and they say they don’t want a particular treatment, it doesn’t mean that the physician just gives up there. It’s actually the responsibility of the physician, both morally and legally to say, “Look, this is the best course of action. This is going to be important for your long-term health.” But of course that creates other difficulties because the reason why the child maybe objecting is because of religious or other kind of reasons. But the point is that doctors still have a role to play in advising children and their guardians, their parents, as to what the best course of action is.

SR: So our advice is read beyond the headlines because many headlines are saying 7-year-old’s now get decisions on medical care, and look carefully. It’s up to the doctor and the parent to involve the child so that they understand their medical care and at the appropriate time can take complete adult care themselves. So, work with your doctor who works with your child and please read MedShadow at medshadow.org.

Tylenol in Pregnancy: Real Concern or Unnecessary Fear?

Acetaminophen, better known under the brand name Tylenol, is an over-the-counter pain- and fever-reducing medication that is generally considered safe to use, even during pregnancy. In recent years, however, a slew of studies have cast some doubt on its safety during pregnancy. Some have claimed use of acetaminophen during pregnancy is linked to autism, ADHD (attention deficit/hyperactivity disorder) and behavioral issues in children.

While this may raise alarm bells for parents, it is important to understand how these studies were conducted in coming to their conclusions. In many cases, a closer examination of the data reveals that the risks have been overstated.

There have been 6 studies on this topic dating back to 2013 — the most recent came out just last month. All of these studies have reached similar conclusions, linking acetaminophen use during pregnancy to various behavioral issues in children.

FDA: No Clear Evidence Linking Tylenol to Developmental Issues

However, after conducting a review in January 2015 of studies to date, the FDA concluded that the results of the studies were too limited to make any definitive recommendations. Hal C. Lawrence, MD, executive vice president and CEO of the American College of Obstetricians and Gynecologists (ACOG), agrees.

The JAMA Pediatrics study in August “and other studies that have been conducted in the past, show no clear evidence that proves a direct relationship between the prudent use of acetaminophen during any trimester and developmental issues in children,” he tells MedShadow.

Let’s take a closer look at that JAMA Pediatrics study, which created scary headlines with the conclusion that behavioral problems were 20% to 45% more common in children whose moms took acetaminophen during pregnancy. The women were asked while pregnant about their acetaminophen use, but interestingly, were never asked how much they took or why. Also, the women who took Tylenol were more likely to have smoked or drank during the pregnancy, and more likely to have underlying psychiatric issues -– all factors that could influence behavior in their offspring.

the difference in the relative risk between women who did and did not take acetaminophen is extremely small.

As NPR pointed out, when these observations were factored in, the increase in behavioral problems in those whose mothers took acetaminophen greatly diminished, and even disappeared in some subgroups, compared to women who never took Tylenol.

Overall, the study found that a little less than 5% of the children examined in the study had behavioral problems. But only 2 percentage points separated those whose mothers had taken acetaminophen compared to those who hadn’t. In other words, the difference in the relative risk between women who did and did not take acetaminophen is extremely small.

Limitations in the Studies

Another limitation of many of these studies is that although they were based on interviews, many times, they were asked about acetaminophen use after their pregnancy. Studies that ask people to recall drugs they took a long time in the past are often inaccurate due to faulty memory.

The PLoS One study is perhaps the most significant evidence to date as it evaluates several medications — aspirin, antacids, NSAIDs (non-steroidal anti-inflammatory drugs), antibiotics and acetaminophen — whereas a majority of studies have only assessed the one medication. But again, this study showed a correlation, not a causation, between acetaminophen use and behavioral problems in children, and there could be other confounding factors involved.

All of these studies have “several limitations as it is not clear what dose of acetaminophen the mothers took, how long they took it, and for what reason. This is all critical information that is missing in order to begin to ascertain a cause and effect,” says Lawrence.

Therefore, “patients should not be frightened away from the many benefits of acetaminophen. The ACOG and obstetricians and gynecologists across the country have always identified acetaminophen as one of the only safe pain relievers for women during pregnancy,” he adds.

Behavioral disorders are a concern for parents as they affect 10-15% of children globally, with ADHD the most widely studied disorder. However, it is important to recognize that “behavioral disorders are multifactorial and very difficult to associate with a singular cause,” says Lawrence. “The brain does not stop developing until at least 15 months of age, which leaves room for children to be exposed to a number of factors that could potentially lead to behavioral issues.”

One important point to recognize in this discussion is that because acetaminophen is considered so safe, it is one of the most popular medications that pregnant women take. Between 40% and 65% of women in the studies said they used it during pregnancy. This compares to other commonly used medications during pregnancy, such as antibiotics (23.5%), antacids (17.4%), aspirin (5.3%) and NSAIDs (1.3%).

“The takeaways here are that physicians should not change clinical practice until definitive prospective research is done,” Lawrence notes. “And, as always, any medication taken during pregnancy should be used only as needed, in moderation, and after the expectant mother has consulted with her doctor.”