The safety and efficacy of methylphenidate (MPH) in 60 children and adolescents with PDD and behavioral difficulties (such as hyperactivity, impulsiveness and distractibility) will be evaluated in a multi-dose, 4-week randomized, crossover, placebo-controlled study. The MPH study has three parts: a Test-Dose Period, a Double-Blind trial and an 8-Week Extension Period (open-label). After a screening visit, eligible children will start a 1-week Test-Dose Period. During this week, each child will be given the three MPH doses that are used in the Double-Blind trial to make sure there are no serious side effects. If problems are encountered at the high dose level, that dose will not be given in the Double-Blind phase. The Double-Blind phase lasts 4 weeks and consists of three different MPH dose levels and a week of placebo. Each treatment/dose is given for 1 week, and neither the researcher nor the participants' families will know whether the medication is placebo or MPH. Children who do well during this phase will continue on the best dose of MPH (determined during the Double-Blind phase) for an additional eight weeks (open-label).
Those who do not show significant improvement during the Double-Blind phase, do not tolerate MPH during the Test Dose Period, or are not able to take MPH before beginning the study are offered open-label treatment with guanfacine for 8 weeks.
Prior to randomization in the MPH trial OR entry into the open-label guanfacine trial, there will be a medication-free period for children who are currently on medication. The withdrawal will be conducted in clinically appropriate way (depending on drug and duration of treatment) to minimize withdrawal effects. This period is to establish a drug-free baseline measurement and to minimize drug-drug interaction. No participant will be withdrawn from a currently effective medication.
