One antipsychotic held its benefit for two years; the other lost ground
STUDY: Chung AKK et al, Front Pharmacol 2026
STUDY TYPE: Randomized controlled trial (single-blind, three-arm)
FUNDING: Independent
Background
Cocaine and methamphetamine can trigger psychosis that sometimes persists into schizophrenia. Antipsychotics are standard treatment, but there’s little long-term data on which drug works best, or for how long.
The Study
- 165 adults with methamphetamine or cocaine-induced psychosis in Hong Kong, randomized 1:1:2 to aripiprazole, paliperidone, or treatment-as-usual, with flexible oral or injectable dosing.
- Clinical Global Impression scores were tracked over 24 months; 70% completed the 12-month primary assessment, 54% completed 24 months.
Results
Aripiprazole improved psychosis severity more than usual care at both 12 and 24 months (effect size 0.38 at 24 months); paliperidone never separated from usual care on severity.
Both drugs outperformed usual care on improvement and efficacy at 1 years, but only aripiprazole kept that advantage at 2 years. Paliperidone patients also tested positive for stimulants more often (76% versus 47%) and fared worse on cognition compared to aripiprazole.
Side Effects
Side-effect burden was mild and similar across groups, though paliperidone caused more weight gain.
Limitations
Enrollment fell 30% short of target due to COVID-19, there was no placebo arm, and the open-label second year may have colored the ratings.
Practice Implications
- Consider aripiprazole for meth- or cocaine-induced psychosis needing a maintenance antipsychotic.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
