Stimulant Medications for ADHD: What’s Old Is New (Again)

How do you make sense of all the medication choices out there?

Posted Mar 11, 2019

Once you know you have ADHD, you face a series of choices. The first choice is whether to use medication or exclusively non-medication approaches. So far in this blog, we have focused primarily on non-medication approaches. But medications do play an important role for many patients with ADHD and can be extremely effective at alleviating symptoms. Many ADHD patients notice a profound difference in the way their mind works when taking medications versus when they don’t — so much so that they describe the first time they took the correct medication as an “Aha!” moment: “Wow! This is really different.  So this is how everyone else goes through their day!” 

But how do you find the “correct” medication?  That used to be simple because there was only one choice — Ritalin — take it or leave it. But now? There are many options to choose from, with several new medications released just in the last year. That’s good: You and your doctor can find a pill that works perfectly for you. But the sheer number of different drug choices can be daunting. In today’s post, we’ll discuss a few of the newer options out there and help you make sense of the differences between them.

If you decide to try a medication for ADHD, the next major fork in the road is choosing whether to take a stimulant or non-stimulant. Stimulants are more commonly prescribed and they probably work better for most people. A major difference is that stimulants work just “for the day." The stimulant pill you take on Monday morning will wear off sometime later the same day. By Monday evening, you’ll be back to your usual “ADHD-self," and when you wake up on Tuesday morning, you will have to decide whether to take a pill again to get through Tuesday.  

In contrast, non-stimulant medications are taken every day and build up in your system over time. Once they take effect, they continue to work 24/7 until you stop taking them — after which it takes at least a day or so, if not longer, for them to completely wear off. All these medications — stimulants and non-stimulants — can have unwanted side effects (the side effects of stimulants differ from non-stimulants).

Although there are some novel non-stimulant medications in the R&D pipeline, the latest drugs to hit the ADHD market fall into the stimulant category, so that is what we will focus on in today’s post.

All ADHD stimulant medications are based on just four chemicals, corresponding to two types of closely related compounds: methylphenidate (Ritalin) and its cousin dexmethylphenidate (Focalin), versus amphetamine (Adderall) and its cousin lisdexamphetamine (Vyvanse). The newest ADHD medications contain these same chemicals (or very slight variations on them) but use new compositions or pill technologies to release active ingredient(s) at different rates or time intervals. This may make a difference for some patients — either for “evenness” of response or for side effects.

New methylphenidate-based drugs:

All these drugs are conceptually similar to one that’s been available for years called Concerta. Concerta is long-acting Ritalin (methylphenidate). Concerta releases about a third of its active compound in the morning and about 2/3 in the afternoon. Compared to Concerta, the newer medications release methylphenidate either in a different AM-to-PM ratio or more evenly over the course of the day. 

Aptensio XR: Releases a little more drug in the morning (about 40%) with the remaining 60% a few hours later.

Cotempla: Releases the drug steadily over the course of the day. This feature may be associated with less appetite suppression.

Quillivant/Quillichew: Conceptually similar to Cotempla, this is designed to release methylphenidate steadily over the day. Quillicant is a liquid, Quillichew a chewable. As with Cotempla, this medication may cause less appetite suppression than Concerta.

New amphetamine-based drugs:

All of these drugs are conceptually similar to a medication that’s been available for years called Adderall (short-acting) or Adderall XR (extended-release).  

Adzenys XR ODT: This uses a similar pill technology to Cotempla but contains amphetamine instead of methylphenidate. It releases the drug steadily over the course of the day, which is generally associated with less appetite suppression.

Dyanavel XR: This is extended-release amphetamine in liquid form - so the dose can be adjusted precisely “to the drop.” Clinical evidence suggests that after an adjustment period of a few weeks it also leads to less appetite suppression than some other formulations.

Evekeo/Zenzedi: Like many complex chemicals, amphetamine can occur in two mirror-image forms (enantiomers) — that bear the same spatial relationship as your right and left hands. This is important because the “right-” and “left”-handed versions of medicinal chemicals can have different biological activities and side effect profiles. Adderall contains a mixture of 75% “right-handed” dextroamphetamine and 25% “left-handed” levoamphetamine. The two newer drugs contain different ratios of these amphetamine enantiomers: Evekeo is a 50:50 left/right blend, whereas Zenzedi is 100% “right-handed” dextroamphetamine. So both Evekeo and Zenzedi are very similar to short-acting Adderall, but some patients may notice slight, but significant, differences in their responses to each.

Mydayis:  You can think of this as “super-extended Adderall XR." Adderall XR releases amphetamine in two spurts: immediately after you take it and then again four hours later. This works well for many patients but not everybody and some patients find they need to take a “booster” of short-acting Adderall late in the day once Adderall XR wears off. Mydayis is formulated to contain a third release time, so it lasts even longer than Adderall XR. This can be particularly helpful for busy workers or students who need a longer-acting medication than Adderall XR but for whom it’s inconvenient to take a late afternoon booster pill — or for whom the booster strategy leads to side-effects from “ups and downs” in their medication levels.

Bottom line: The latest entries in the ADHD medication field are not revolutionary; they are mostly tweaks of existing stimulant drugs designed to be released differently or to last longer, over the course of a day. But this is not to say they are unimportant. The reality is that most patients, once they find a medicine that works for them, go through a process of trial-and-error to figure out the best way to take it each day: how big a dose, how many times, and exactly when. These new medications afford patients and doctors additional dosing alternatives that for some patients may make a difference in the overall quality of response, in getting an all-day response from a single pill, or in the severity of side effects including appetite suppression and insomnia

But speaking of “afford” — these new pills are generally far more expensive than older alternatives. Are they worth it? Only you can determine that, but as you do so remember that in this increasingly crowded and competitive field of ADHD medications and manufacturers, you can almost always find some sort of discount coupon online.