How high a dose of stimulant medication in adult attention deficit hyperactivity disorder?

Objective: This paper examines clinical and neuroscientific evidence to address the question whether high doses of stimulant drugs offer additional advantages in the treatment of adult attention deficit hyperactivity disorder (ADHD) and at what cost. It attempts to arrive at a reasonable upper limit of dosage for clinical purposes. Method: The study involves a selective review of the treatment studies of ADHD in children and adults and an examination of the pharmacokinetic and pharmacodynamic data on psychostimulants in humans and animals. Results and Conclusions: The clinical and experimental data justify the use of chronic low-dose stimulant treatment of ADHD in adults, with the recommended upper limit of dose being 1 mg/kg for methylphenidate and 0.5 mg/kg for dexamphetamine. There is no empirical evidence of greater improvement with higher doses and any beneficial effect is likely to be compromised by the adverse effects, some of which can be very serious. The recommended doses should be exceeded only after careful consideration and objective documentation of beneficial and adverse consequences. Monitoring of drug levels in blood may be of some value for compliance or pharmacokinetic considerations, as there is a direct relationship between blood and brain levels as well as dopamine transporter occupancy. These recommendations are tentative and further clinical research is warranted.