title: Methylphenidate combined with aripiprazole in children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder: a randomized crossover trial.
abstract: In clinical samples, juvenile bipolar disorder (JBPD) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder (ADHD). Clinical trials assessing combined psychopharmacological interventions in this population are scarce, and methylphenidate (MPH) may worsen manic symptoms. We conducted a randomized crossover trial with MPH and placebo (2 weeks each) combined with aripiprazole in children and adolescents (n = 16; 8-17 years old) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinically significant symptoms of ADHD. ADHD, manic, and depressive symptoms were assessed by means of standard scales. Fourteen out of the 16 subjects completed the trial. No significant differences between the effects of methylphenidate and placebo were detected in ADHD (F(1, 43.22) = 0.00; p = 0.97) or manic (F(1, 40.19) = 0.93; p = 0.34) symptoms. Significant improvement in depressive symptoms was observed in the MPH group (F(1,19.03) = 7.75; p = 0.01) according to a secondary self-reported outcome measure. One patient using aripiprazole and MPH discontinued the trial due to the onset of a severe mixed episode. No other significant adverse events were observed. Although MPH did not worsen manic symptoms, it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole. Further investigations are warranted. This study is registered at www.clinicaltrials.gov under the identifier NCT00305370.
authors.affiliation: Juvenile Bipolar Disorder Outpatient Program (ProCAB), Division of Child and Adolescent Psychiatry, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul , Brasil .
authors.forename: Cristian Patrick
authors.initials: CP
authors.lastname: Zeni
authors.forename: Silzá
authors.initials: S
authors.lastname: Tramontina
authors.forename: Carla Ruffoni
authors.initials: CR
authors.lastname: Ketzer
authors.forename: Gabriel Ferreira
authors.initials: GF
authors.lastname: Pheula
authors.forename: Luis Augusto
authors.initials: LA
authors.lastname: Rohde
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000627:therapeutic use; D000068180:Aripiprazole; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy*; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D010879:Piperazines; D015363:Quinolones; D008774:Methylphenidate; D000068180:Aripiprazole