Hold the lumateperone, but read on for better options
STUDY: Grant JE et al, Clin Neuropharm 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: IntraCellular Pharmaceuticals
Background
Antipsychotics have limited benefits and elevated risks in borderline personality disorder (BPD). Olanzapine sought FDA approval here, but its 10 trials barely crossed the threshold for limited symptoms like aggression, impulsivity, and interpersonal sensitivity. Aripiprazole (15 mg) had the strongest signal in a new meta-analysis, improving aggression and paranoia at around 15 mg per day. This trial tested lumateperone, which has a mix of serotonin, dopamine, and glutamatergic effects.
The Study
60 adults with BPD were randomized to lumateperone 42 mg/day or placebo for 8 weeks. 45% of the lumateperone group dropped out early, mostly from side effects, versus 13% on placebo.
Lumateperone didn’t separate from placebo on the primary outcome, a BPD scale (ZAN-BPD), with marked improvement in both placebo and medication. The disability scale (SDS) did improve more with lumateperone, but this is likely a random blip amidst a sea of measures.
Side Effects
Headache, tingling, hot flashes, and ringing in the ears.
Limitations
Small sample, high dropout, industry funding.
Practice Implications
- No med stands out for borderline personality disorder.
- Here’s an updated list of the top contenders, and I lean toward the one with the fewest risks (omega-3).
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
