An Alzheimer’s drug improves cognition after mania
STUDY: Mirzazadeh H et al, Journal of Affective Disorders 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Independent
Background
Most of the disability in bipolar disorder is caused by cognitive symptoms, not the mood episodes themselves. Memantine improved cognition in earlier studies of bipolar, but they were either uncontrolled or secondary analyses. Other studies tested it for symptoms of mania and depression, but there was no clear therapeutic signal.
This is randomized trial to tested it directly for cognition in bipolar disorder, shortly after recovery from mania.
The Study
- Sixty-three adults with bipolar I disorder, hospitalized during an acute manic episode, were randomized to memantine (titrated to 20 mg/day) or placebo, added to lithium-olanzapine combo (no drop-outs).
- Global cognition was measured with the Neurocognitive Assessment Battery (NuCog) and executive function with the Frontal Assessment Battery (FAB), at baseline, week 6, and week 18.
- Titration: 5 mg/day for 10 days, 10 mg/day for 10 days, then 20 mg/day.
Results
Memantine surpassed placebo on most measures in this small trial. The effect wasn’t obvious at 6 weeks but became clear by 18 weeks.
Global cognition scores rose about 9 points more with memantine at week 6, and nearly 13 points more by week 18. Executive function didn’t separate from placebo at week 6, but by week 18 memantine patients scored better there.
The gains kept building over time rather than plateauing, with memantine showing particular strength in attention, memory, vasoconstriction ability, and executive subtests like mental flexibility and inhibitory control (the Go–No Go test).
Limitations
Small, single-center, and not powered for its primary analysis. Mood was still resolving during follow-up, so some of the cognitive gain may reflect faster mood recovery rather than a direct cognitive effect. No functional outcomes were tracked, and there’s no long-term data past 18 weeks.
Practice Implications
A small trial, with some past support, but needs replication.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
