Methylphenidate vs. amphetamine: Comparative review

This article compares the two most common medications for Attention-Deficit/Hyperactivity Disorder (ADHD), using data from controlled studies. Medline and Psychinfo searches were done for 1984-1996 with the key words methylphenidate (MPH) and amphetamine (AMP); these were supplemented with known prior and recent literature. Of 92 animal studies found, 15 showed clear differences between the two drugs. Ten reports of controlled crossover ADHD clinical trials (three in the same sample) and a dozen other articles comparing the two drugs in humans were found. MPH is a pure re-uptake inhibitor of catecholamines, especially dopamine; AMP also releases catecholamines. Lab animals showed differential interactions with other drugs and with behavioral paradigms. Human response profiles are noncongruent. An ADHD patient who fails on one stimulant should try the other. Of 174 patients in the 6 clearest crossover studies, 48 responded better to AMP, 27 to MPH, and at least 72 to both, which is an 87+% overall response rate if both are tried. All crossovers, except the one with comorbid Tourette's, showed a nonsignificant tendency for AMP superiority in response rate. Summed data suggest suspected differences in side effects (AMP more sleep and appetite loss and exacerbation of tics in comorbid Tourette's, MPH possibly more depression/apathy and stomachaches) and effects on comorbid disorders (AMP better for conduct/oppositional symptoms, MPH for Tourette's and possibly learning disorder (LD). Most of the clinical differences are tendencies rather than statistically significant.