Stimulants for Inattentive ADHD, a Comparison

When you read about stimulant therapy for ADHD, the Ritalin class of medication (methyphenidate) and the Adderall class of medication (Dextroamphetamine) are spoken of as if they were almost the same medication. The medical indications for these medications and their documented side effect profiles look almost identical. In fact they are different. The way they work on the brain is slightly different and their side effect profile is different but you do not often hear about these differences.

How They Work On the Brain

Both of these medication groups work on the neurotransmitter actions in the brain but something about the way the Adderall class of medication acts causes a greater improvement in symptoms of ADHD when compared to the Ritalin class of medication. Unfortunately, that news must be balanced with the news that the Adderall class of medication has a somewhat uglier side effect picture.

Several recent studies (citations below) have shown that Ritalin improves ADHD by "by both up-regulation of dysfunctional fronto-striato-thalamo-cerebellar and parieto-temporal attention networks and down-regulation of hyper-sensitive orbitofrontal activation for reward processing".

The Adderall class of medication does this as well but it is metabolized differently which results in a stronger action from the dopaminergic nerves. My understanding of the actions of these medicines is that Adderall's action results in the brain having more available and more efficiently used dopamine as opposed to Ritalin's action which is primarily to have the brain more efficiently use existing dopamine. The problem is that Adderall's increased dopamine signaling causes an oxidative reaction which can be stressful to the dopaminergic nerves and cause them permanent damage.

Some new studies have recently shown that "Amphetamine administration to rodents has been shown to provoke significant neurotoxicity involving dopaminergic nerve terminal degeneration." This has not been found, as far as I could tell from my research, to be a problem with the Ritalin class of medicines.

Obviously the actions of long term amphetamine use in humans needs to be further explored but as of this moment, there is reason to believe that, in terms of neurotoxicity, the Ritalin class may be a bit safer.

Side Effect Profile

Though both these medicine classes can on occasion cause mood changes, a few raandomized control studies have shown that the Dextroamphetamine class of medicine causes significantly more severe irritability, proneness to crying, anxiousness, sadness/unhappiness and nightmares when compared to the Methyphenidate. The Dextroamphetamines are slightly more likely to cause tics than the Methyphenidate class though this side effect can be seen with both medication classes.

Some individuals report that the action of the Adderall class of medication feels 'stronger' than Ritalin even when it is taken using equivalent doses. The Adderall class of medications has shown a slight advantage in symptom control (especially in the realm of attention) when compared to methylphenidate. These advantages, given that they have been consistently documented might clearly point to a preference to using Adderall over Ritalin. The advantages have to be balanced, however, with the fact that dextroamphetamine may be more likely to be associated with neurotoxicity and side effects.

Neuropharmacology. 2009 Dec;57(7-8):640-52. Epub 2009 Aug 26.
Methylphenidate normalizes activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task.

Biopolymers. 2007 Aug 5-15;86(5-6):437-46.
Amphetamine effects on brain protein structure and oxidative stress as revealed by FTIR micro spectroscopy.

J Dev Behav Pediatr. 2006 Feb;27(1):1-10.

Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

Pediatrics. 1997 Oct;100(4):662-6.
Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial.