Are ADHD Stimulant Drugs Bad for your Heart?

Potential Cardiovascular Risks of ADHD Medications

Given the rapid rise in prescription stimulant medications for ADHD, potential concerns surrounding the side effects of these medications has been a hot topic of recent interest. News alerts like to mention the potential dangers of these drugs, and "natural health" websites are often even quicker to point out these flaws (often to the point of exaggeration).

While it is a medical fact that stimulant medications do carry certain health risks, I believe that the big question we should be asking ourselves surrounding this issue is not whether amphetamine or amphetamine-like medications are dangerous for us, but rather how can we minimize these negative effects of these substances and keep their usage as safe as possible? After all, untreated ADHD can cause enough problems in and of itself (I will describe some of these lesser known consequences in a later post).

There was a relatively recent article (2006) in the New England Journal of Medicine titled ADHD Drugs and Cardiovascular Risk sought to investigate the overall safety of these stimulant medications for treating ADHD. This article was in the Perspective section of the journal, meaning that this was an opinionated piece. We should always be careful about drawing conclusions based on opinionated sources, but I believe that the author, Steven E. Nissen of the Cardiovascular Medicine division of the Cleveland Clinic and member of the FDA Advisory Committee on ADHD drugs, makes some very important points that are at least worth mentioning.

Some of the key points of the article are summarized as follows:

• The administration of mixed amphetamines (Adderall) and the amphetamine-like compound methylphenidate (Ritalin, Concerta) both raised systolic blood pressure (the higher number) by about 5 mm Hg. Based on other reviews, elevated blood pressure, even of this magnitude can pose as a major cardiovascular threat.

• Taking medications of this class (called sympathomimetic agents) results in a long-term increase in heart rate at potentially dangerous levels.

• Several drugs which are chemically similar to ADHD stimulant medications have been either pulled from the market or are subject to strong medical lobbying efforts for removal. Drugs such as ephedra and phenylpropanolamine (PPA) are both chemically similar to ADHD stimulants and have similar overlapping modes of action. Ephedra has been linked to the deaths of several professional and amateur athletes and a warning has been issued surrounding PPA and increased risks of hemorrhaging and stroke.

• The Adverse Event Reporting System (AERS), which is a database used by the FDA to detect potential risks surrounding medications and other treatments, turned up multiple reports of sudden deaths associated with ADHD stimulant drugs, several which involved individuals with pre-existing cardiovascular defects and conditions. Additionally, a significant number of non-fatal heart difficulties such as heart attacks, irregular heart beats and stroke were observed.

• Many of these reports were "without proper documentation", so the FDA could not make any definitive conclusions from this data. Based on this blogger's opinion, the phrase "without proper documentation" could refer to either data which is not complete to the point of being statistically significant to warrant further action, or information that was disregarded due to minor "technicalities" intrinsic to a bureacratic system. It is neither my place nor my intention to villainize the FDA, but it is important to at least consider this information and keep it tucked away in the backs of our heads.

If the information and conclusions of the article appear bleak to you, that is because they are. Nevertheless, it is important to note that this is one person's opinion, which, although echoed by many, is by no means unanimous. Having said that, I believe that the following steps should be taken for anyone considering stimulant medications for ADHD or a related disorder:

1. A thorough screen of both an individual's background and their family history should be done before starting any type of ADHD stimulant medication.
2. Numerical measurements such as blood pressure and heart rates should be taken frequently and passed on to the individual's physician. Keep in mind that even moderate increases in either of these can pose serious cardiovascular risks over time.
3. For individuals with pre-existing heart problems, these medications should only be taken in cases of severe levels of ADHD (where the risks of non-treatment would be potentially more injurious to the individual than the elevated cardiovascular risks associated with these drugs).
4. Even minor changes and symptoms need to be reported immediately and communicated to a supervising physician.

I believe that, in spite of the information presented in this, as well as other articles, ADHD medications can still be administered safely. However, I also believe that a more stringent set of conditions should be met, especially with regards to an individual's overall cardiovascular health. For those who believe that they fall into the "cardiovascular risk" category, I will soon be outlining some useful strategies to help reduce the potential risks and improve the overall safety of these ADHD medications.

ADHD Medication Recall: Dextroamphetamine Sulfate

ADHD Medications

ETHEX Corp. voluntarily recalls batches of Dextroamphetamine Sulfate

While far from catastrophic, it is worth mentioning that there was a recent recall by some manufacturers of the ADHD stimulant medication Dextroamphetamine Sulfate. Dextroamphetamine, which also goes by the trade name Dexedrine or Dextrostat (by other manufacturers), is a relatively potent stimulant used to treat ADHD and anxiety disorders. ETHEX issued a release to the FDA on Tuesday October 15, 2008 about a recall of the 5 mg tablets of its version of the drug. Tests had shown that a sample of the medication contained oversized tablets that included a noticeably higher dosage than labeled (up to twice as high in some cases).

The good news surrounding this release is that no wholesalers or retailers of the drug have filed reports citing oversized tablets of the 5 mg of the drug (click here for a pictured link to this product). Additionally, the company manufactures 10 mg tablets of the same product, so even an accidental "double dose" (10 mg) of the medication does not exceed the dosing maximum for this particular product line. The frequency of negative side effects is often limited when total dosing is below 15 mg, and the drug typically does not result in severe reactions until around 30 mg (three times the "double dose") is taken.

Hypothetically speaking, an accidental overdose of Dextroamphetamine sulfate could cause an array of symptoms and side effects including an increased heart rate (tachycardia) and elevated blood pressure (hypertension). The risk is increased if antidepressants of the Monoamine Oxidase Inhibitor family (such as Selegiline, Zelapar capsules or transdermal Emsam patches) have been used within two weeks of the dextroamphetamine sulfate medications.

Aside from possible risks for those with current cardiovascular disorders, it is unlikely that any major side effects would occur from taking the occasional oversized capsule. Nevertheless, it raises the concern about medication dosing and how important knowledge regarding the dose-dependant effects of ADHD medications truly are. In a future post, we will explore how different doses of the same medication can often result in vastly different responses in a patient.

ADHD medications

Risperidone Boosts ADHD Stimulant Medication Effects

ADHD Medications

Risperidone Boosts Stimulants' Effectiveness for ADHD and Conduct Disorders

We often search the fine print for ADHD medication labels to see if there are potentially negative drug-drug interactions. However, an equally valid question may be: are there other medications which may boost or augment the effectiveness of an ADHD medication while keeping negative side effects to a minimum? The answer to this question appears to be "yes". We have seen in a previous post how ADHD medications and treatments can often overlap those of co-occurring disorders, such as in bedwetting. We have also seen how Atomoxetine (Strattera) can be an effective treatment option for ADHD and Tourette's. We have also explored the relative safety of ADHD stimulant medications taken during pregnancy. Now we will discuss is which medication strategies are effective for ADHD and comorbid conduct disorders and evaluate the relative safety of these medication combos.

The drug Risperidone (also referred to as Risperdal or Rispen), is a relatively new antipsychotic medication which was released in 1993 for adults and was approved in 2007 as a treatment option for both pediatric schizophrenia and pediatric bipolar disorders. A year prior to this, it was used as a potential treatment medication for pediatric autism. Given the fact that individuals with ADHD are more prone to exhibiting multiple symptoms of these disorders, Risperidone is a potential agent of interest for certain forms of ADHD.

A key study was done in 2004 by MG Aman and colleagues and was published in the Journal of Child and Adolescent Psychopharmacology, which focused on the effects of Risperidone when used in conjunction with other stimulant medications for treating ADHD in children of sub-average IQ's during a 6-week study period. Additionally, differences in behavioral disorders frequently seen alongside ADHD, such as Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) were also monitored by the study.

Although not a stimulant medication itself, the study's findings suggest that Risperidone may prove to be useful in augmenting these stimulant medications' effectiveness for these disorders or combinations of disorders. Additionally, results from the study suggest that Risperidone,by itself is often an effective treatment for hyperactivity and conduct disorders that often occur alongside ADHD. When combined with stimulants, the overall effectiveness is even greater.

Safety-wise, the study found that the use of Risperidone produced no noticeable change in the number of stimulant-related adverse drug effects. The three main ADHD stimulant medications used in the study were Methylphenidate, Pemoline, and Dextroamphetamine, with levels for each medication covering a wide dosage range. It is first important to note that while methylphenidate and dextroamphetamine are both considered to be relatively safe stimulant medications for treating ADHD, Pemoline (Cyclert) is known to be potentially harmful to the liver, and is typically used sparingly, often as a last resort among many physicians. What the study observed, however, is that risperidone, when taken alongside these stimulant medications, does not increase the number or severity of these side effects (Risperidone treatment did result in slightly more weight gain than the placebo controls, but the overall difference was small). This should be taken as good news for those concerned with the overall safety and effectiveness of combining stimulant and non-stimulant medications.

While ADHD stimulant medications and antipsychotic agents have different modes of action and different biological "targets", the results of this study suggest that the two types of medication are often able to work together and improve each other's effectiveness, while incurring minimal side effects. This suggests that for children with both ADHD and some type of oppositional or conduct disorder, prescribing Risperidone along with a stimulant medication such as Ritalin, Concerta or Dexedrine may be a highly effective and relatively safe treatment option.

ADHD medications

ADHD and Bedwetting

ADHD Medications

Treating ADHD Children Who Wet the Bed

It's a classic problem that often puzzles parents of ADHD children. Why does my 13 year old still wet his bed? As it turns out, bed wetting, or enuresis, is a surprisingly common comorbid (co-occurring) disorder to ADHD. Other ADHD comorbid disorders that have been mentioned in previous posts include epilepsy and Tourette's Syndrome.

While there is some evidence that the two disorders share a common underlying cause (the lack of inhibitory behavior present in ADHD could span to poor muscle control), it is interesting to note that the comorbid disorder of bed wetting is connected most strongly to the Inattentive Subtype of ADHD (as opposed to the Hyperactive/Impulsive Subtype or the Combined Subtype).

Furthermore, the use of the tricyclic antidepressant drug Tofranil (Imipramine), which is often used to treat bladder control problems, has also been shown to be an effective medication for treating ADHD in some cases. We will explore this in a bit more detail in a later post, but it is important to remember that enuresis is an unusually common disorder in individuals with ADHD, especially with the Inattentive Subtype in particular. Given the fact that medications used to treat this co-occurring disorder are also sometimes useful in treating ADHD, it is my hope that other existing drugs may be further explored for their role in treating ADHD.

ADHD Medications

Do ADHD Medications Cause Birth Defects?

ADHD Medications and Pregnancy

Do ADHD Medications Cause Birth Defects?

Due to the impulsive tendencies of adults with ADHD (currently thought to be as high as 4% of the general adult population), one would expect higher rates of unplanned pregnancies among this subgroup of the adult population. This is, in fact, often the case. As a result, it is worth investigating whether women with ADHD, who are often on medications are posing hazardous risks to their babies by taking these drugs during pregnancy. Although this area of ADHD medications and birth defects has not been studied extensively, here are some following observations and guidelines to go by:

Since some of the most common primary forms of ADHD medications are amphetamine-based stimulant drugs (such as Adderall), it is necessary to mention the fact that amphetamine usage during pregnancy has been shown to correlate with a reduction in birth weights of these children. However, other factors of growth, such as head size or birth length were unchanged, and the birth weight reduction amounts were often significantly less than a pound compared to newborns of non-users of amphetamines (or less than a 5% difference on average). Another relatively large study done primarily on the stimulant dextroamphetamine (Dexedrine), showed no significant difference in birth weights or the prevalence of birth defects.

For medications such as methylphenidate (Ritalin, Concerta), which is not an amphetamine but rather and amphetamine-like stimulant, no significant evidence has shown any connection to birth defects or lower birth weights. However, one study in which the mothers had taken methylphenidate alongside alcohol, cigarettes and other drugs showed higher rates of birth defects, mental impairments and reductions in birth sizes. However, this study had no adequate group of controls, so the effects of the ADHD drug itself could not be determined. Nevertheless, we must leave room for the possibility that this type of stimulant may worsen birth defects triggered by other maternal patterns of substance abuse.

Some other ADHD medications have not been explored in depth in human mothers, but have been investigated in other mammals. For example, in a study done on the non-stimulant ADHD medication Atomoxetine (Strattera) in pregnant rats, it was shown that weight reduction, impaired bone development, and lower offspring survival rates were tied to high levels of this drug. Of course, this was done on a different mammalian system at doses up to 30 times higher than the recommended optimal levels for humans (on a pound-for-pound basis). An even higher relative dose done on rabbits was shown to interfere with development of the circulatory system with the offspring. However, these levels were shown to be significantly over the relative toxic level of the drug in humans.

As a quick side note, I should mention that a small fraction of the population carries an uncommon form of the genetic region CYP 2D6, which, among other things, is connected to the metabolism or breakdown of the Atomoxetine drug. Individuals with this rare form (which can be determined by genetic screens), may be somewhat more at risk than their counterparts. However, individuals with this genetic form would often exhibit adverse effects to the medication early on, and would likely be placed on a different medicated treatment option.

Based on the overall dearth of information involving ADHD medications and pregnancy, we cannot arrive at any definite conclusions about their relative safety in pregnant or nursing mothers. However, if the connection between these medications and birth defects was significant, the results of some of the aforementioned studies would likely have been much more foreboding. As a result, the use of controlled and prescribed medications at appropriate doses are unlikely to pose any sort of major threat in pregnant or nursing mothers. Nevertheless, certain drugs, although much less common as primary modes of treatment for ADHD can be utilized if potential pregnancy or birth defects are a concern.

Medications such as Bupropion (Wellbutrin), have been shown to be useful in treating some forms of ADHD and may be especially effective for individuals who also suffer from depression or those who want to quit smoking. Unfortunately, one of the negative side effects of this medication is that it can increase the risk of seizures (for more information on ADHD and seizures, please check out this earlier post). Nevertheless, aside from some of these potential risks, it appears that Bupropion poses a noticeably smaller role than most stimulants in triggering birth defects.

Additionally, the drug Clonidine, which has shown to be effective in treating ADHD in several cases (especially those cases in which an ADHD comorbid disorder such as Tourette's Syndrome), is also less likely to cause birth defects than stimulants. Clonidine, which also goes by the brand names Catapres and Dixarit, is also used as a treatment for hypertension and can also be used in conjunction with stimulant medications to treat ADHD individuals. This is often done because of the sedative effects of the drug, which, when administered strategically before bedtime, can help calm things down a bit by offsetting the stimulant effects of other ADHD medications. One major caveat with Clonidine, however, is that sudden withdrawal or discontinuation of the drug can cause a rapid and dangerous spike in blood pressure. If Clonidine is to be discontinued, the individual must be gradually weaned off the drug to avoid these negative and harmful side effects.

It is my hope that some of this information will serve as good news to pregnant or soon-to-be pregnant individuals with ADHD. While the information contained here should never be a substitute for personal medical advice, I want you to leave with the fact that, at least as of now, the overall risks of birth defects or complications remain relatively low for most ADHD drugs. This is especially true when other non-prescribed chemical substances are avoided.

ADHD medications and Pregnancy