To understand medications for ADHD treatment, you need to keep two neurochemicals in mind: dopamine and norepinephrine. Both are important for attention and focus, for the functioning of the pre-frontal cortex region of the brain. Think of it as the secretary of the brain: It’s the locus of what’s referred to as executive functioning—how you plan, how you organize, how you execute.
These two chemicals are critical for those functions, dopamine for decreasing signals from the external stimuli that might be distracting to you, and norepinephrine for improving the signal you’re trying to focus on, to pay attention to. When you take Ritalin, Adderall, or any other stimulant medication, what it does is help bring up the levels of dopamine and norepinephrine.
If you get optimal levels of dopamine and norepinephrine, you are pretty focused. But if you get too much, you can stress out the brain. Then you look almost like the ADHD is worse. There’s a perception, especially among teenagers: “Oh, if it’s good at this dose, more will be even better.” No, it won’t. It can feel worse, and you can get a lot of side effects. So trying to get that right balance is what’s key.
When it comes to stimulant medications for ADHD there are a lot of alternatives to choose from, and they’re not all created equal. So if we don’t think one med is working as well as we would like, we want to try something else. Children can respond very differently to different formulations.
Effectiveness of medications
If you have ADHD, studies show there’s an over 80% chance that you are going to respond to medication. Within that group, 50% will respond equally well to the two main classes of ADHD medications: methylphenidate (Ritalin and other brands) or amphetamine (Adderall and other brands). Of the other 50%, half will do better on methylphenidate and half on amphetamine.
There are also several medications that aren’t based on stimulants but they are considerably less effective in treating symptoms.
The challenge with stimulant medicines is how to deliver an effective dose over a desirable period of time. When Ritalin was first used to treat ADHD in 1961, it was with a kindergartener or a first-grader in mind. It lasted three or four hours. But kindergarteners now have homework, and the older kids get, the longer they need to stay focused to succeed in school and get along with their friends and family. So technology has been developed to make the medication release gradually, peaking at the desired time, so users don’t have to remember to take pills multiple times a day.
Ritalin, the granddaddy of them all, is a short-acting formulation of methylphenidate that lasts about 3-4 hours. Focalin is another form of methylphenidate that also lasts about 4 hours. Both of these medications begin to work about 30-45 minutes after taking them. For children who have trouble swallowing pills, this medication can be crushed and mixed with foods. There is also a liquid and a chewable tablet form of the short-acting methylphenidate.
Other forms of methylphenidate that have been engineered to release optimally over a particular period of time.
First up is Concerta, one of the longest–acting methylphenidate medications on the market, lasting 8 to 12 hours, the equivalent of 3 tablets of Ritalin. What’s unique about Concerta is that it has a hard shell; you can’t chew it or open it. You’ve got to swallow it whole, which can be a problem for some kids. It has triple-release: First, there’s a coating of medicine on the outside, so within 10 or 15 minutes you’ll be getting some effects of the medication. On the inside, there’s a push compartment filled with a polymer fiber that expands like a sponge as it gets wet, and pushes out the medicine through a laser hole on one end. The capsule itself doesn’t get absorbed.
Concerta has two compartments of the drug, 30% in the first, and 70% in the second. This is called an “ascending dose,” and it is designed to offset a decline in the impact of the medication that can occur the second half of the day. But for some kids, it might be too long.
There are also capsules filled with medication in beads. What’s good about these is that for kids who can’t swallow pills, you can open up the capsule and sprinkle it on a spoonful of applesauce, yogurt or Nutella.
One of the beaded forms is Metadate CD, which lasts about six to eight hours. It has two kinds of beads in it, also in an “ascending dose”—30% are quick release, to work the first four hours, and 70% slow release, for the latter four hours.
Ritalin-LA also has beads, but they’re 50-50—that is, half the beads are going to be released immediately, to peak in the morning, the other half in the afternoon, for a total of six to eight hours. So you have much more of a two-equal-phases effect on focus and attention.
Aptensio XR and Focalin XR are also capsules filled with medication that can be opened and mixed with food. They typically work longer than Ritalin LA or Metadate CD.
For kids who have trouble swallowing capsules and even have trouble with beads, there are liquid forms of methylphenidate medication. Quillivant XR is a long-acting formulation that I often describe as “liquid Concerta,” and is a good alternative. The liquid formulation may also allow more precise dose adjustment or “titration.”
Quillichew ER is a chewable long–acting formulation of methylphenidate that can last up to 8 hours.
Full day medications: A new medication, Azstaryz, is a form of dexmethylphenidate (like focalin) that can last 9-12 hours and has less appetite suppression, but isn’t always covered by insurance until you have tried other meds first
And then there’s Daytrana, which is the methylphenidate patch. Basically, the patch is like a carpet of medication that’s embedded in this adhesive, so you peel the liner off, and you put it on the hip, because the hip is the area that has less muscle, so the medicine will get into the body quicker.
In developing the patch, the company thought two things. First, it’s good for kids who can’t swallow pills. And second, you bypass the gut, so it doesn’t have to be metabolized to get into your bloodstream. It will go through the skin, right into the bloodstream.
Now, that said, it doesn’t work right away. Since it absorbs slowly, it takes about two hours to get up to therapeutic level. But once it’s there, it stays pretty constant until you actually take it off. So another thing that parents like is that they feel they can have more control over when the medicine ends by taking off the patch. If you want to take it off at 2:00pm one day but at 5:00pm the other, you have that ability. Usually the medicine will drop in the bloodstream an hour and a half to two hours after you take off the patch.
Kids often aren’t as enthusiastic. Some kids don’t like the idea of wearing a patch. A lot of ADHD kids are tactile-sensitive, and they’ll take it off. And when you take it off it doesn’t go back on. But I have some college kids who like the patch because they don’t have to worry about taking medicine later in the day; they can just keep it on as long as they want to. If they forget to take it off it doesn’t matter: There’s only about nine to 10 hours of medication in the patch, so they’re still able to fall asleep.
On the amphetamine side, Adderall, Evekeo, Zenzedi and Dexedrine are all short-acting forms of amphetamines, that take effect about 30-45 minutes after taking them and they are effective for 3-4 hours. Amphetamines tend to be slightly more potent than methylphenidate and last a little longer, but in general the effects are similar to methylphenidate.
As with methylphenidate, some preparations of amphetamines have been created to release the medication over a greater period of time, extending the duration of the effect of the medication. This is of great benefit when trying to provide a response that lasts through a school day (typically 6-8 hours). Some of these compounds take effect as quickly as the short-acting forms of these medications.
Adderall XR is the longer-lasting form, designed to be effective for 10-12 hours. It’s a capsule with beads that are 50-50, so 50% of them are immediate release, and the other 50% are delayed release. The capsule can be opened and the beads mixed with food.
Vyvanse is amphetamine plus an extra compound called lysine, which attaches itself to the active ingredient in Adderall, amphetamine, creating an extra step that the body has to go through to cut it off, to make it active. That means Vyvanse lasts very long—up to 14 hours. That could be too long for a seven-year-old, but if you’re in high school or college, or an adult, it could be great. It’s not beads; it’s just a powdered medicine. But it’s going to have a consistent release, without peaks and troughs.
Dexedrine Spansule is the long-acting form of Dexedrine and typically lasts about 6-8 hours.
Dynavel XR is a long-acting liquid form of amphetamine. It can have an effect that lasts as long as 10-12 hours.
Adzenys XR-ODT is a tablet that dissolves in your mouth and doesn’t need to be swallowed. It has a duration of response of 10-12 hours.
Mydayis is a long acting form of amphetamine (same make up as Vyvanse) that can last up to 16 hours, but can suppress appetite for a longer period of time, and affect sleep if it lasts too long.
Stimulant medications can be very effective in reducing symptoms of ADHD, but some kids do experience uncomfortable or harmful side effects. When side effects become a problem, we try to change the dosage, the release formula, or the type of medication your child is taking. The goal is to determine what will give him the most benefit, with the least side effects.
The key problems to be on the lookout for:
- Sleep problems
- Decreased appetite
- Delayed growth
- Headaches and stomachaches
- Rebound (irritability when the medication wears off)
- Moodiness and irritability
To get an accurate picture of side effects, we need to establish your child’s baseline before he starts taking the medication. For instance, some kids with ADHD have a hard time falling asleep to begin with. Some kids with ADHD are very picky eaters to begin with.
Identifying existing problems helps us avoid blaming the medicine for problems that were already there.
Two key factors in side effects
Getting the right dosage is important for minimizing side effects. Stimulant medications work by bringing up the levels of two brain chemicals, dopamine and norepinephrine. If your child gets the right levels of dopamine and norepinephrine, he will be pretty focused. But if he gets too much, it can stress out the brain, and cause negative side effects.
It’s also important to note that there are two groups of ADHD medications, each based on a different stimulants:
- methylphenidate-based medications: Ritalin, Methylin, Concerta, Metadate, Daytrana Patch
- dextroamphetamine-based medications: Adderall, Vyvanse, and Dexedrine.
Some children respond differently to those two groups of medications. Some even respond differently to different release formulas—the speed in which the medication goes into the blood stream—of the same basic medicine. Short-acting formulas are released immediately, and last about 4 hours. Long-acting formulas, which release the medication gradually, last up to 14 hours. So when children get unwanted side effects we often try switching medications and formulas.
If medication is keeping your child awake into the wee hours, it’s because the medication is still active at bedtime. If he’s taking a short-acting formula, it may mean that he is taking a second or third dose too late in the day, so it hasn’t worn off by bedtime. If he’s taking medication that lasts 12 or 14 hours, it may help to try one that’s not quite as long-acting.
Sleep issues caused by the medication tend to get better over time, so it’s worth giving your child four to six weeks to see if he adjusts to what he’s taking.
Trouble going to sleep may also be caused by kids being too stimulated at bedtime—often by doing something on the computer—to calm themselves down. If the medication has worn off, it may be their ADHD keeping them awake.
There are also some medicines we can try for sleep problems: Melatonin can be effective (use a small dose, 0.5-1 mg about 2 hours prior to desired bedtime). Benadryl was commonly used until a decade ago, but it caused a hangover effect the next day, and kids did not feel as alert as they should.
Extended release medicines can cause eating problems. These drugs peak about four hours after they’re taken. So some kids take the medication before breakfast and then find they lose their appetites at lunchtime.
You may be able to help by encouraging your child to eat whenever he does feel hungry. He can have a good breakfast before the medicine has kicked in, and at the end of the day when the medicine is wearing off. Try to get them to eat a small, protein/fat dense snack at lunch if they aren’t hungry for a full meal (i.e. a protein bar.)
If it’s a real problem for your child, breaks from medicines on holidays or weekends may help, or switch to the immediate-release tablets, which will wear off by lunch.
Some kids, particularly boys, grow more slowly when they’re taking stimulant medication, especially in first year. But studies show that by the second and third year they catch up, gaining the growth they’d be expected to have gaining. And boys who took weekend breaks and summer vacations from the medication didn’t show that decrease in growth in the first year.
This side effect does not show up in girls.
Nausea and headaches
These problems tend to dissipate within a few weeks of beginning medication, and can be minimized by having your child take the medication with food, and in some cases by changing the dosage or schedule.
Some parents describe something we call the “rebound effect.” After the medication wears off, their child becomes very irritable and aggressive. Sometimes parents tell me, “Every day at 4:30, I know it’s going to happen.”
What’s happening is that the medication is leaving the receptors in the brain too quickly. One way to try to avoid rebound, if it’s a problem, is by adding a smaller dose a half hour before it usually happens, to help your child ease off the medication more gradually.
Sometimes rebound can be a sign that the dose is too high, and needs to be adjusted. It also may be an indication that this particular medicine doesn’t work well in your child’s body, and we may want to try a different medication or a different formula.
Lastly, with kids who rebound, we want to ask whether there might be something else going on. They might have underlying anxiety or mood issues that come into play when they come off their ADHD medicine. We don’t want to miss other things that could be muddying the equation.
That rebound period is usually relatively brief, and is a good time to let your child have some free time to do whatever calms them- running around outside, a little iPad time, crafting, etc.
Some children who take stimulant medication develop tics. When that happens, the first thing we might want to do is lower the dose of the medication or try a different stimulant, to see if another medication will work without the tics. Tics will go away once the medication is stopped, it is not a permanent effect.
If that doesn’t work, we may try a non-stimulant medication, which affects the brain in a different way. There are two types that can help alleviate symptoms of ADHD (though they aren’t as potent as stimulants) but are less likely to cause tics:
- Atomoxetine (sold as Strattera) is in a class of drugs called norepinephrine reuptake inhibitors. Norepinephrine is a natural substance in the brain that is needed to control behavior.
- Clonidine (Catapres, Nexicon) and guanfacine (Tenex) are what is called alpha-adrenergic agonists. These medications were developed to lower high blood pressure, but at the doses we use to treat kids with ADHD they rarely affect blood pressure.
When a stimulant dose is too high for a child he may begin to look sedated or zombie-like, or tearful and irritable. If this happens we need to adjust the prescription until we find the right dose.
But there is a small subset of kids with ADHD who seem to get moody and irritable when they take stimulant medications, even if we have the best possible dose. It usually happens right away, as soon as they start taking the medication, and goes away immediately when they stop taking it.
If this happens with your child, once again we can try switching to a different stimulant, since some kids react differently to those based on methylphenidate and those based on amphetamine. If that doesn’t work, a non-stimulant medication is a possibility.
Of course we have to keep in mind that kids who have ADHD can also develop depression. In fact they are higher risk for developing major depressive disorder than other kids. The good news is that kids can be safely treated for both disorders at the same time, though we don’t recommend treating mood problems that are a side effect of stimulant meds with another medication.
There was some concern back in 2005 and 2006, based on a study of pooled data, with Adderall in particular, about increasing the risk of what’s called sudden death. Sudden cardiac death usually means below the age of 21—some studies show the age of 30—and these are cases like young athletes who die on the track or the football field or the basketball court.
But when they went back and looked at all the data, it turned out that being on the medication does not increase your risk of sudden death, all the way up to 64 years of age. It’s not greater than that of the general population.
Nonetheless, before we start a child on medication, we take a careful cardiac history. We always ask for a history of sudden death in the family on either side, and for the child’s personal cardiac history. At the baseline, you want to check blood pressure, and if there’s any family history, or if there’s any indication of cardiac symptoms, then that patient should have a cardiac workup before he starts stimulant medication.
In sum, most of the side effects of stimulant medication can be managed by carefully adjusting the dosage and schedule and giving kids time to get used to to the medication. In cases where they continue, and cause real problems for your child, we look to other treatments.