A Randomized, Placebo-Controlled Trial of Three Fixed Dosages of Prolonged-Release OROS Methylphenidate in Adults with Attention-Deficit/Hyperactivity Disorder

Background There is increasing recognition of attention-deficit/hyperactivity disorder (ADHD) in adults and the need to evaluate efficacy and safety of methylphenidate treatment in these patients. Methods In this double-blind trial, 401 adults with ADHD (218 men; 18–63 years) were randomly assigned to receive prolonged-release osmotic release oral system (OROS) methylphenidate (18 mg, 36 mg, or 72 mg/day) or placebo for 5 weeks. Primary outcome was change in total score on Connersʹ Adult ADHD Rating Scale (CAARS: investigator-rated) at end point compared with baseline. Adverse events, vital signs, and laboratory parameters were assessed. Results Treatment with 18-mg, 36-mg, and 72-mg/day prolonged-release methylphenidate, compared with placebo, was associated with significantly larger improvement in CAARS total symptom score from baseline to end point than placebo: mean change −10.6 (p = .01), −11.5 (p = .01), and −13.7 (p< .001) versus −7.6, respectively. Responders (≥30% decrease) were 50.5%, 48.5%, and 59.6% versus 27.4% (p< .001). Other efficacy measures also showed improvements. Incidence of adverse events was 75%, 76%, and 82% in 18-mg, 36-mg, and 72-mg/day groups, respectively, and 66% in placebo; most frequent included decreased appetite (25% methylphenidate; 7% placebo) and headache (21% methylphenidate; 18% placebo). In methylphenidate-treated patients, 4.3% discontinued due to adverse event; one serious adverse event was possibly related to study drug. Blood pressure and pulse increased at week 1 and then remained stable through week 5. Conclusions Prolonged-release methylphenidate is an effective treatment of ADHD in adults, with a safety profile consistent with methylphenidate use in pediatrics.