Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: a 4-week, randomized, double-blind, placebo-controlled, parallel-group study.

BACKGROUND: The ability to recognize and diagnose attention-deficit/hyperactivity disorder (ADHD) has increased in recent years. The persistence of ADHD symptoms puts adolescents with ADHD at risk for long-term adverse psychosocial outcomes.

OBJECTIVE: The primary goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) in the management of adolescents with ADHD.

METHODS: This was a 4-week, randomized, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-titration study. Adolescents aged 13 to 17 years with ADHD were randomized to 1 of 4 active treatments (MAS XR 10, 20, 30 or 40 mg/d) or to placebo. All doses were given in the morning. This study used a forced-dose-titration design in which patients randomized to the 10-mg/d group received 1 dose of 10 mg/d for 4 weeks. Patients randomized to the 20-mg/d group received 1 dose of 10 mg/d for the first week and 1 dose of 20 mg/d for the remaining weeks; patients randomized to the 30-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, and 1 dose of 30 mg/d for the remaining 2 weeks; and patients randomized to the 40-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, 1 dose of 30 mg/d for the third week, and 1 dose of 40 mg/d for the fourth week. The primary efficacy measure was change from baseline to end point in the ADHD Rating Scale-IV (ADHD-RS-IV) score. The secondary efficacy measure was the score on the Clinical Global Impressions-Improvement (CGI-I) scale for ADHD. ADHD-RS-IV total scores were analyzed post hoc in patients with low baseline ADHD-RS-IV severity (ie, patients with baseline ADHD-RS-IV total scores less than the median) and high baseline ADHD-RS-IV severity (ie, patients with baseline ADHD-RS-IV total scores greater than the median). Safety was assessed by recording adverse events, vital signs, and body weight at all study visits and 30 days after drug discontinuation.

RESULTS: Of the 287 randomized adolescents, 258 completed the study. The intent-to-treat (ITT) population included 278 patients. The majority of patients were male (65.5%) and white (73.7%) The mean weight (57.8 kg [127.1 lb]) at baseline and the mean height (163.8 cm [64.5 in]) at screening were comparable across all MAS XR treatment groups. Patients in the placebo group had a mean weight of 59.8 kg (131.6 lb) and a mean height of 166.1 cm (65.4 in). Most (56.5%) of the patients had ADHD combined inattentive/hyperactive-impulsive subtype. Two hundred nineteen (78.8%) patients were treatment naive, and 59 (21.2%) had received treatment for ADHD within 30 days before screening. ITT analysis of the ADHD-RS-IV revealed statistically significant (P < 0.001) improvement in mean ADHD-RS-IV total scores in all 4 MAS XR treatment groups, compared with placebo, at all weeks throughout the 4-week study; the mean change from baseline to end point was -17.8 in the MAS XR 10- to 40-mg/d groups and -9.4 in the placebo group. Significant treatment effects were observed in both the ADHD-RS-IV inattentive (P < 0.001) and hyperactive-impulsive (P < 0.001) subscales from baseline. In patients with low baseline ADHD-RS-IV severity, statistically significantly (P < or = 0.01) greater improvements were observed in the MAS XR 20-, 30-, and 40-mg/d groups than in the placebo group; in patients with high baseline ADHD-RS-IV severity, statistically significantly (P < or = 0.02) greater improvements were observed in all active treatment groups compared with placebo. On the CGI-I scale at end point, a higher percentage of adolescents in all MAS XR treatment groups were considered improved (MAS XR 10 mg/d, 51.9% [P < 0.01]; 20 mg/d, 66.0% [P < 0.001]; 30 mg/d, 70.7% [P < 0.001]; 40 mg/d, 63.9% [P < 0.001]) compared with adolescents receiving placebo (26.9%). The most common adverse events in patients receiving MAS XR versus placebo were anorexia/decreased appetite (35.6% vs 1.9%), headache (16.3% vs 22.2%), insomnia (12.0% vs 3.7%), abdominal pain (10.7% vs 1.9%), and weight loss (9.4% vs 0%). Most adverse events were mild or moderate in intensity (97.5%); no serious adverse events were reported.

CONCLUSIONS: The adolescents with ADHD treated with 10- to 40-mg/d MAS XR up to 4 weeks had significant improvements in ADHD symptoms compared with those who received placebo. Results of this study suggest that once-daily dosing with MAS XR up to 40 mg was effective and well tolerated for the management of ADHD in these adolescents.