Clinical trial NCT00305370: Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
Official title: Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD: A Randomized Cross-Over Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Attention Deficit Hyperactivity Disorder
Keywords: clinical trial
aripiprazole
methylphenidate
Bipolar Disorder
Attention-Deficit Hyperactivity Disorder
ADHD
Lead sponsor: Federal University of Rio Grande do Sul
Sponsor class: OTHER
First posted: 2006-03-21
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: There is a scarcity of clinical trials assessing the effects of medications in children with bipolar disorder. This study aims to assess the efficacy of Aripiprazole associated with Methylphenidate (MPH)for the treatment of children and adolescents with bipolar disorder comorbid with ADHD who improve in maniac symptoms while receiving aripiprazole but did not have an adequate response in ADHD symptoms. The study design is a 4-week randomized, double blind, cross-over group trial. Patients were randomized to aripiprazole + MPH or aripiprazole + placebo. The main hypothesis is: Aripiprazole + MPH will significantly reduce ADHD scores compared to aripiprazole + placebo.

Detailed description: Bipolar disorder (BD) is a chronic disorder that severely affects the normal development of children and adolescents. The disorder is associated with high rates of suicide and high-risk behaviors like sexual promiscuity and drug abuse. Bipolar disorder in children is also associated with high rates of comorbidity, especially with Attention-Deficit Hyperactivity Disorder (ADHD). There is a scarcity of clinical trials assessing the effects of medications in children with BD. Moreover, the frequent presence of comorbid ADHD might determine lower response to treatment. Aripiprazole is a novel anti-psychotic drug. Its mechanism of action seems to be related to a stabilization of dopaminergic transmission, acting as a partial agonist especially in dopaminergic D2 receptors. It also has effects in 5-HT1a serotonergic receptors. Thus, it might have a promising effect in children and adolescents with comorbid BD and ADHD. A retrospective chart review, recently published, suggests the efficacy of this drug in children with BD. This study aims to assess the efficacy of Aripiprazole associated with Methylphenidate (MPH) for the treatment of 20 children and adolescents (age range: 8 to 17 years-old) with Bipolar Disorder comorbid with ADHD who improve in maniac symptoms while receiving aripiprazole but did not have an adequate response in ADHD symptoms. The study design is a 4-week randomized, double blind, cross-over group trial. Patients were randomized to aripiprazole + MPH or aripiprazole + placebo. The hypotheses are: 1) Aripiprazole + MPH will significantly reduce ADHD scores compared to aripiprazole + placebo. 2) Patients receiving aripiprazole + MPH will not deteriorate in maniac symptoms.

Eligibility criteria: Inclusion Criteria:

* Age: 8 -17
* BD type I or II comorbid with ADHD
* Reduction of maniac symptoms (30% reduction in the YMRS scores and/or CGI scores ≤ 2)while using aripiprazole during a previous study (NCT00116259)without improvement of ADHD symptoms (reduction in ADHD symptoms \< 30% in the SNAP-IV). Those receiving placebo in the previous protocol will receive a 6- week open label treatment with aripiprazole. The same threshold for reducing maniac symptoms and absence of response in ADHD symptoms will be used.

Exclusion Criteria:

* IQ \< 70
* Pregnancy or absence of a contraceptive method in fertile girls
* Diagnoses: pervasive development disorder, schizophrenia, drug abuse or dependency
* Risk of suicide or homicide
* Clinical condition that might interfere in the study
* Known sensibility to aripiprazole

Primary outcomes:
measure: Scores in the SNAP-IV (ADHD)
measure: Scores in the Young Mania Rating Scale (BD)
measure: Weight
Secondary outcomes:
measure: Scores in CGI
measure: Scores in the CMRS-P
measure: Scores in the CDRS
measure: Scores in the Kutcher Adolescent Depression Scale
measure: Scores of quality of life (YQOL-R)
measure: Report of side events
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: ADHD Outpatient Program
state: RS
Study officials:
affiliation: Federal University of Rio Grande do Sul
name: Luis A Rohde, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry. 2005 Jan;162(1):58-64. doi: 10.1176/appi.ajp.162.1.58.
citation: Biederman J, McDonnell MA, Wozniak J, Spencer T, Aleardi M, Falzone R, Mick E. Aripiprazole in the treatment of pediatric bipolar disorder: a systematic chart review. CNS Spectr. 2005 Feb;10(2):141-8. doi: 10.1017/s1092852900019489.
citation: Zeni CP, Tramontina S, Ketzer CR, Pheula GF, Rohde LA. Methylphenidate combined with aripiprazole in children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder: a randomized crossover trial. J Child Adolesc Psychopharmacol. 2009 Oct;19(5):553-61. doi: 10.1089/cap.2009.0037.