A year-long trial reports large gains, but no one got a stimulant first
STUDY: Abbasi E et al, BMC Psychiatry 2026
STUDY TYPE: Randomized controlled trial
FUNDING: Independent
Background
Risperidone is often prescribed off label for aggressive, oppositional children with ADHD. It blocks dopamine and serotonin receptors and is FDA-approved for irritability in autism. Long-term placebo-controlled data in ADHD are lacking, and this one fills that gap.
The Study
- 104 children ages 3 to 12 with severe ADHD and oppositional or aggressive behavior despite behavioral therapy.
- Randomized to risperidone (up to 1.5 mg/day) or placebo for 48 weeks; 94 finished.
- Both groups received parent training. Stimulants were not allowed, and 80% had never taken one.
- Primary outcome: clinician-rated ADHD scale (ADHD-RS-IV).
Results
ADHD scores improved 46% with risperidone vs 8% with placebo. Response rates were 71% versus 22% (NNT 2). Parents saw the biggest change in oppositional behavior.
The effect sizes were very large (Cohen’s d 1.84), about triple what earlier risperidone trials found.
Side Effects
- Weight gain: 3.8 kg versus 1.2 kg; glucose, cholesterol, and triglycerides rose; metabolic effects tend to be worse in children than adults.
- Prolactin rose 10 ng/mL.
- Somnolence (25% vs 9%), extrapyramidal symptoms (6% vs 0%), increased appetite (21% vs 4%).
- Risperidone can also cause tardive dyskinesia, acute dystonia, akathisia, and other side effects that did not show up in this trial.
Limitations
- Treating clinicians were not blinded though raters were.
- Single site, registered after the fact.
Practice Implications
- While this trial shows that risperidone improves aggression in ADHD, we already knew that from Blader’s 2021 trial, which used a more realistic scenario, adding risperidone to a stimulant.
- In Blader’s trial, valproate worked equally well, and was better tolerated.
- Blader’s trial also taught us that ADHD-related aggression usually improves with methylphenidate and behavioral therapy. Most of the patients enrolled didn’t need the second phase of treatment, so start with the basics before adding in antipsychotics or anticonvulsants.
- Omega-3, clonidine, and possibly guanfacine also have anti-aggressive effects and ADHD benefits.
- Watch for conversion to bipolar and psychosis in children with ADHD and aggression, and remember that lithium has five controlled trials in conduct disorder and one in ADHD.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
