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Objective: This study investigated the safety and efficacy of adding the atypical antipsychotic quetiapine to ongoing OROS methylphenidate treatment for adolescents with comorbid ADHD and severe aggression that were incompletely responsive to methylphenidate monotherapy.

Method: Participants aged 12–16 years were enrolled in a prospective, open-label trial consisting of 3 weeks of OROS methylphenidate monotherapy titrated to 54 mg/day, followed by 9 weeks of combination treatment with quetiapine and methylphenidate. Twenty-four out of thirty participants failed to meet criteria for significant improvement (Clinical Global Improvement-Severity [CGI-S] and Rating of Aggression Against People and Property [RAAPP] scale scores of 1 or 2 and ADHD-Rating Scale: Investigator Administered and Scored [ADHD-RS-I] score less than 50% of baseline score) with methylphenidate treatment alone and received combined treatment.

Results: Investigator and parent ratings of ADHD symptoms, aggression, and global functioning improved significantly during both methylphenidate monotherapy treatment and during combined methylphenidate–quetiapine treatment. At the conclusion of combined treatment, 42% of the sample met all criteria for clinically significant improvement and 79% showed minimal aggression. Mild and transient sedation was reported by about half the cases. Weight loss (0.9 kg) during methylphenidate treatment was offset by weight gain (1.2 kg) during combination treatment.

Conclusion: Quetiapine addition to methylphenidate was effective in reducing ADHD and aggression in individuals who did not respond sufficiently (based on CGI-S, RAAPP, and ADHD-RS-I criteria for significant improvement) to OROS methylphenidate alone at a 54-mg/day dose.