henry copeland:

Crappy studies

Unfortunately, the extant studies on side effect risk of the stimulants used for ADHD treatment have many limitations. All have been restricted to relatively short durations of exposure; and most are based on an assumption that a dose of methylphenidate is equivalent to half of an equal dose of amphetamine. Therefore, amphetamine is administered at 50% of the methylphenidate dose using fixed-dose designs, rather than titrating to a pre-determined efficacy endpoint before comparing adverse events. Most studies have not incorporated measurement of plasma drug level achieved although few relationships between these common adverse events and plasma levels have been noted 15. Nevertheless, it is potentially important that treatment within approved dose ranges with amphetamines, especially newer extended-release formulations, have produced residual low, but detectable, steady-state blood levels up to 24 h after administration. Thus many individuals experience some degree of continuous drug exposure. Although not tested, this finding suggests that cardiovascular complications, which have been associated with both normal aging and amphetamine abuse in young addicts, may appear earlier in older adults receiving maintenance amphetamine treatment 26. Regarding the detection of risk for uncommon or rare severe psychological or behavioral reactions to stimulants, controlled studies have not been large enough to pinpoint risk factors or determine differential risk by treatment assignment. Finally, a common observation across studies of the pharmacokinetics, pharmacodynamics, and safety profiles of amphetamine is the high degree of interindividual variability across most measures and endpoints. This variability calls for additional caution in application of the increasingly common practice of prescribing stimulants concurrent with use of other psychotropic medications 27, 28.
- www.ncbi.nlm.nih.gov