Attention-deficit/hyperactivity disorder (ADHD) has long been treated with the stimulant medication methylphenidate in an immediate-release formula. The disadvantage of this medication is the very short half-life and the necessity for multiple dosing during the day. This becomes an issue when the medication is used to treat school-aged children. The optimal dosing schedule is three times in a 12-hour period, which would require that the medication be administered during school hours. This may cause embarrassment for the student and also has implications with regard to administering a controlled substance during school hours. An initial attempt to create sustained-release methylphenidate was unsuccessful because the formula reduced the effectiveness of the medication. Recently, however, a new sustained-release formula has been developed. Swanson and colleagues studied the pharmacokinetics and pharmacodynamics of methylphenidate in the new sustained-released formula.
The study participants were children seven to 13 years of age who met criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) for the diagnosis of ADHD. In addition, these children were already being treated with immediate-release methylphenidate in a dosage of 5 to 15 mg two to three times per day. A university laboratory school evaluated the children multiple times on nonconsecutive days using a teachers' assessment tool. In the first phase of the study, children were given capsules containing active medication or placebo in 30-minute intervals to determine the validity of a sustained-release preparation. In the second phase, the pharmacokinetics and pharmacodynamics of a new once-a-day methylphenidate were assessed.
The first phase of the study demonstrated that the ascending dose that mirrored a sustained-release preparation was similar to the standard three-times-per-day dosage of methylphenidate. In the pharmacokinetic study of the new once-a-day formula of methylphenidate, plasma levels increased rapidly, peaking seven to nine hours after administration. The results of the pharmacodynamic studies of the new formula matched those of the three-times-per-day dosage of methylphenidate in terms of onset and duration of efficacy.
The authors conclude that the new once-a-day formula of methylphenidate has a rapid onset and long duration of efficacy after a single morning dose. This provides children with ADHD an option for once-a-day treatment of their symptoms.