Risperidone vs Aripiprazole for Weight Gain in Children with Autism

Overseen By Sally Furukawa

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must not be taking: Atypical antipsychotics

Disqualifiers: Age 18+, No autism diagnosis

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 months

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, aripiprazole (Abilify) and risperidone (Risperdal), to determine which causes more weight gain in children with autism. Both drugs are approved for managing behavior issues in these children. The trial takes place at the Vanderbilt clinic as part of regular medical care. Eligible participants have autism, behavior problems, and have not previously used these medications. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments benefit a broader range of patients.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you must not have used atypical antipsychotics before.

What is the safety track record for these treatments?

Previous studies have shown that both aripiprazole and risperidone have some side effects but are generally well-tolerated in children with autism.

Research on risperidone found that it can lead to weight gain. In one study, children gained an average of 2.7 kg, or about 6 pounds, over a certain period. Other side effects include increased appetite, fatigue, and sometimes shaking.

Aripiprazole also causes weight gain, though less than risperidone. One study noted an average increase of about 1.13 kg, or 2.5 pounds. Common side effects include feeling very relaxed or sleepy, fatigue, and increased appetite.

Both medications have FDA approval for treating behavioral issues in children with autism. This approval indicates they are considered safe when used as directed, though monitoring for weight gain is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments, Risperidone and Aripiprazole, because they offer different ways to manage weight gain in children with autism, a common side effect of autism medications. Risperidone works by blocking dopamine and serotonin receptors in the brain, which can help with mood and behavior but also tends to increase appetite. On the other hand, Aripiprazole is unique because it acts as a partial agonist at dopamine receptors, meaning it can stabilize dopamine levels in the brain, potentially leading to less weight gain compared to other medications. By comparing these two approaches, researchers aim to better understand how these drugs impact weight, helping to tailor treatment plans for kids with autism.

What evidence suggests that this trial's treatments could be effective for weight gain in children with autism?

This trial will compare the effects of Risperidone and Aripiprazole on weight gain in children with autism. Research has shown that both Risperidone, administered to participants in one arm of this trial, and Aripiprazole, given to participants in another arm, can cause weight gain. Specifically, studies found that children taking Risperidone can gain between 2.7 to 5.4 kilograms over a few months, often due to increased appetite. Aripiprazole can also lead to weight gain, but usually less than Risperidone, with some studies indicating around 2.0 kilograms. Both medications help manage behavioral issues in autism, but weight gain is a common side effect to consider. ^{1 2 3 5 6}

Who Is on the Research Team?

Angela Maxwell-Horn, M.D.

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for children up to 17 years old with autism spectrum disorder who have behavioral issues and haven't used atypical antipsychotics before. They must be patients at the Vanderbilt clinic.

Inclusion Criteria

I am 17 years old or younger.

I have never taken atypical antipsychotics.

Diagnosed with autism

Exclusion Criteria

I have used medication for severe mental health issues.

Not diagnosed with autism

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either aripiprazole or risperidone for the treatment of behavioral dysregulation

3 months

Follow-up

Participants are monitored for weight gain at a follow-up visit

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Aripiprazole
• Risperidone

Trial Overview The study compares weight gain in children with autism when treated with two FDA approved medications: Risperidone and Aripiprazole, during routine clinical care.

How Is the Trial Designed?

Group I: Treatment with Risperidone Active Control 1 Intervention

Patients prescribed Risperidone

Group II: Treatment with Aripiprazole Active Control 1 Intervention

Patients prescribed Aripiprazole

Aripiprazole is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Abilify for:

• Irritability associated with autism spectrum disorder in children aged 6 to 17

Approved in European Union as Abilify for:

• Schizophrenia
• Bipolar I disorder
• Major depressive disorder
• Irritability associated with autistic disorder

Approved in Canada as Abilify for:

• Schizophrenia
• Bipolar I disorder
• Major depressive disorder
• Irritability associated with autistic disorder

Approved in Japan as Abilify for:

• Schizophrenia
• Bipolar disorder
• Major depressive disorder
• Irritability associated with pervasive developmental disorders

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

In a study of 82 children aged 2 to 13 with autism spectrum disorder (ASD), treatment with risperidone or aripiprazole led to significant improvements in challenging behaviors, with 96% of patients showing notable improvement according to the Clinical Global Impression scale.

While the medications were effective, some side effects were noted, including elevated prolactin levels in 12 patients and weight gain in 2 patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Core Signs and Symptoms in Children with Autism Spectrum Disorder Improved after Starting Risperidone and Aripiprazole in Combination with Standard Supportive Therapies: A Large, Single-Center, Retrospective Case Series. Alsayouf, HA., Talo, H., Biddappa, ML.[2023]

In a clinical trial involving 59 children and adolescents with autism spectrum disorders, both aripiprazole and risperidone were effective in reducing irritability, as measured by the Aberrant Behavior Checklist (ABC) scores over 2 months.

The study found that the rates of adverse effects were similar for both medications, indicating that aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) have comparable safety profiles, allowing treatment choice to be based on patient preference and clinical considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. Ghanizadeh, A., Sahraeizadeh, A., Berk, M.[2022]

Both risperidone and aripiprazole are effective in reducing the severity of autism symptoms, including repetitive behaviors and social withdrawal, based on an overview of 22 systematic reviews involving children aged 12 years or younger.

While these medications show moderate efficacy in the short term, they are also associated with potential metabolic and neurological side effects, highlighting the need for careful monitoring and further research with longer follow-up periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risperidone and aripiprazole for autism spectrum disorder in children: an overview of systematic reviews. Fieiras, C., Chen, MH., Escobar Liquitay, CM., et al.[2023]

The SPACe 2: STAR study is a randomized controlled trial involving 140 children aged 6 to 18, aimed at determining if therapeutic drug monitoring (TDM) of antipsychotics like risperidone and aripiprazole can prevent significant weight gain while maintaining treatment effectiveness for autism-related behavioral issues.

This study will be the first of its kind to evaluate the impact of TDM on weight management and metabolic side effects in children taking antipsychotics, with primary outcomes measured by BMI z-scores at 24 weeks, providing crucial insights for optimizing treatment in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of therapeutic drug monitoring of risperidone and aripiprazole on weight gain in children and adolescents: the SPACe 2: STAR (trial) protocol of an international multicentre randomised controlled trial. Hermans, RA., Ringeling, LT., Liang, K., et al.[2022]

In a study of 142 children and young adults with autism spectrum disorders treated with risperidone or aripiprazole, both medications led to significant increases in body mass index (BMI) and BMI Z-scores over time.

There was no significant difference in the rate of BMI or BMI Z-score change between the two treatment groups, indicating that both medications have similar effects on weight gain in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body mass index change in autism spectrum disorders: comparison of treatment with risperidone and aripiprazole. Wink, LK., Early, M., Schaefer, T., et al.[2021]

In a retrospective case study of 10 children under 4 years old with autism spectrum disorder (ASD), treatment with risperidone or aripiprazole led to significant improvements in both irritability and core ASD symptoms, with 60% of patients showing minimal-to-no symptoms after treatment.

The only notable adverse effect was excessive weight gain in two patients, highlighting the need for careful monitoring, but overall, the findings suggest that pharmacological intervention may be beneficial for very young children with ASD, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risperidone or Aripiprazole Can Resolve Autism Core Signs and Symptoms in Young Children: Case Study. Alsayouf, HA., Talo, H., Biddappa, ML., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7120220/

Aripiprazole for autism spectrum disorders (ASD) - PMC Weight gain and metabolic side effects. The three studies also reported data on weight gain. As weight gain is a common occurrence for patients ...

2. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15800

Towards precision dosing of aripiprazole in children and ... Aripiprazole has been proven to significantly reduce ASD-related irritability and aggression in patients, as demonstrated in several randomized ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37222228/

Linking blood levels to weight gain and effectiveness Towards precision dosing of aripiprazole in children and adolescents with autism spectrum disorder: Linking blood levels to weight gain and effectiveness. Br J ...

4. advancedautism.com advancedautism.com/post/abilify-for-autism

Abilify for Autism Short-term studies, typically lasting 8 weeks, suggest aripiprazole can help manage challenging behaviors effectively. However, longer-term data ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923002179

Aripiprazole in Autism Spectrum Disorders and Fragile X ... In this report, the mean weight gain was 2.0 kg on aripiprazole compared to 0.8 kg on a placebo at week 8. Several post-hoc analyses of pooled data from the two ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3121213/

Safety and Tolerability of Aripiprazole in the Treatment ... Common adverse events with aripiprazole versus placebo included sedation (20.8% vs 4.0%), fatigue (16.5% vs 2.0%), vomiting (13.7% vs 6.9%), increased appetite ...