To understand Adderall, we have to start with an older medication, Obetrol. Remember that Obetrol was an early form of amphetamine, used to treat obesity in the 1940s, 1950s, and 1960s. Initially, Obetrol contained meth-amphetamine, which is now better known as “speed,” and this may have explained its initial popularity. Even though the meth-amphetamine was removed from Obetrol, in 1973 the FDA with- drew its approval because of nationwide concerns that amphetamines had significant abuse potential.
However, although the name Obetrol has faded from history, its legacy has persisted. Shire Pharmaceuticals acquired the rights to Obetrol in 1994. Initially, Obetrol was a mixture of the two stereoiso- mers (mirror images: dextro-amphetamine and levo-amphetamine) in a 50 percent–50 percent ratio. Shire changed the ratios so that a single pill contained 75 percent dextro-amphetamine and 25 percent levo- amphetamine and then went back to the FDA. Because of this change in the ratio of the stereoisomers, this new formulation could be approved as a new brand-name medication.
But this time, Shire did not ask that Obetrol be approved for the treatment of obesity. Instead, Shire asked the FDA to approve it as a treatment for ADHD, which the FDA did in 1996.
Shire Pharmaceuticals made one more change to this new formula- tion: it changed the name of Obetrol to Adderall (short for “ADD for all”).
Dexedrine consists only of dextro-amphetamine., whereas Adderall is a combination of 75 percent dextro-amphetamine and 25 percent levo-amphetamine. However, the inclusion of levo-amphetamine in any ratio has never been shown to be superior in any way to simple dextro- amphetamine alone.
Further, in Adderall, the two isomers of amphetamine (dextro and levo) are also combined to different salts. However, the different salts add absolutely nothing. Once the medication is absorbed, the salt is stripped away from the amphetamine molecule and discarded. Nevertheless, Adderall is often referred to as mixed amphetamine salts (MAS).
So, Adderall is really Dexedrine (dextro-amphetamine) combined with levo-amphetamine and with different salts. But what benefit do you get from such a concoction?
As it turns out, zero.
Some studies have shown that levo-amphetamine is a little better than dextro-amphetamine at reducing hyperactivity and aggressiveness, but it has little significant effect in the brain in enhancing attention in children with ADHD.1 Another study showed that dextro-amphetamine was “consistently superior to levo-amphetamine.” Further, researchers found that dextro-amphetamine began to take effect during the first few days, whereas levo-amphetamine would take up to three weeks before any benefit could be seen, and then the benefit was minimal.2
But there is more. Levo-amphetamine is also more likely to cause side effects (appetite reduction and mild increase in blood pressure and heart rate), and the mixture of salts affixed to the amphetamine molecule has absolutely no therapeutic benefit.
Because dextro-amphetamine is much more effective than levo- amphetamine,3 one-third of Adderall is virtually useless. And the
Sixteen Brand-Name Amphetamine Medications to Treat ADHD
mixed amphetamine salts are nothing more than window dressing. So why go to all the trouble to produce mixed amphetamine salts in this new ratio of stereoisomers when it has no advantage over plain old Dexedrine (dextro-amphetamine)? By now, you should be able to answer this question. These machinations made Adderall unique, in a chemical way, allowing the FDA to grant its production as a brand-name medication.
John S. Markowitz, a scientist who has researched amphetamines extensively, stated, “The reasoning behind the inclusion of disparate amounts of dextro- and levo-amphetamine, and the range of salt forms incorporated, appears to have been one more of pharmaceutical conve- nience than scientific rationale.”4
When I asked this same question of a representative from Shire Pharmaceuticals, he spoke extensively about the subtle differences of the left- and right-handed versions of amphetamine, but in the end, he admitted, “It was a business decision.” What he meant was that because Obetrol had already been formulated and had been approved by the FDA, it could be presented as another treatment for ADHD without having to go through all the effort to come up with a new medication.
My clinical experience with Adderall is that Adderall and Dexedrine are equally effective for the treatment of ADHD, but I do see a differ- ence in side effects. Adderall is more likely to cause irritability when it wears off than the methylphenidate preparations. It got to the point that when I saw a new patient, I occasionally received this complaint, “My son has been diagnosed with ADHD and medication has really helped him, but he gets so angry when he gets home from school. We’re wor- ried about him.”
I will often say, “Let me guess, Adderall?,” and the parents nod their heads. This irritability effect of Adderall has a name. Gina Pera, who has written extensively about ADHD on her blog, calls this medi- cation “Madderall.”5
Adderall XR is the extended-release version of Adderall. It employs a similar coated bead technology used in Ritalin LA, Focalin XR, and Metadate CD to last about eight hours. It was approved by the FDA in 2001.
Adderall and Adderall XR are very effective medications to treat ADHD, but they offer no real benefit over the much less expensive
Dexedrine and Dexedrine Spansules and their generics.6 Adderall is usually covered by insurance, but without insurance, it is an expensive drug that shows no advantage over the much less expensive Dexedrine Spansule with the added burden of more side effects. Nevertheless, in 2016, it was the forty-fifth most prescribed medication in the United States, with more than seventeen million prescriptions per year.7