A third antipsychotic option finds a positive trial
STUDY: Findling RL et al, J Am Acad Child Adolesc Psychiatry 2026
STUDY TYPE: Randomized controlled trial
FUNDING: AbbVie
Background
Risperidone and aripiprazole are the only FDA-approved drugs for irritability in autism, but tolerability problems often limit their use. This trial tested cariprazine (Vraylar), a D3-preferring dopamine and serotonin 5-HT1A partial agonist approved in adults for schizophrenia, bipolar I (mania or depression), and as antidepressant augmentation in major depression.
The Study
- 161 youth ages 5 to 17 with autism and moderate-to-severe irritability; 126 completed.
- Randomized to cariprazine (0.75 to 3 mg/day by age and weight) or placebo for 8 weeks.
- Primary outcome: caregiver-rated Irritability scale (ABC-I), covering tantrums, aggression, and self-injury.
Results
Irritability scores fell 14.9 points with cariprazine and 11.3 with placebo, a modest effect (effect size 0.42). Clinicians rated 69% as much improved, versus 38% on placebo (NNT 3). Anxiety and caregiver strain did not improve significantly. Most children settled on 1.5 mg/day.
Side Effects
- Sleepiness: 17% versus 1%.
- Weight gain: 2.4 kg versus 1.0 kg.
- More shifts to high LDL cholesterol; no rise in prolactin and no akathisia.
- 7% stopped for side effects, versus 1% on placebo.
Limitations
Short term, industry funded.
Practice Implications
- Reserve antipsychotics for problematic (eg, physical, dangerous) aggression. Use therapy and parent training first line.
- Clonidine and omega-3 also have anti-aggressive properties with better safety profiles.
- Among the antipsychotics, aripiprazole has the best balance of efficacy and tolerability in this population. Cariprazine also works, with less prolactin risk than risperidone.
- It is now available as 0.5 mg and 0.75 mg. Can also start every other day (it has a long half life).
- Learn more in our Carlat autism interview with Josh Feder.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
