TOPLINE

Patients with systemic lupus erythematosus (SLE) and measurable cognitive deficits who received memantine for 12 weeks showed greater improvements in objective cognitive performance, especially immediate memory, than those who received placebo.

METHODOLOGY

• Researchers conducted a randomized double-blind phase 2 study to assess whether memantine improved cognitive function in patients with SLE who had measurable neuropsychological impairment.
• They included adults with SLE who scored 85 or lower on a standard neuropsychological test called the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The trial was conducted at three sites across the US.
• A total of 56 patients were randomly assigned to receive memantine or placebo for 12 weeks. Memantine was started at 10 mg/d and increased weekly to a maximum of 40 mg/d by week 4, with participants continuing their maximum tolerated dose through week 12.
• Overall, 43 patients completed the 12-week treatment period; their mean age was 43.4 years and 93% were women.
• The primary outcome was the change in the RBANS total score from baseline to week 12, with a gain of ≥ 8 points considered a clinically meaningful improvement.

TAKEAWAY

• Patients who received memantine gained more points in the RBANS total score than those who received placebo (median gain, 8 vs 5 points; P = .032).
• The improvement was particularly pronounced in the immediate memory domain for patients who received memantine vs placebo (median gain, 18.5 vs 7 points; P = .023).
• A higher percentage of patients who received memantine achieved a clinically meaningful improvement in RBANS total score than those who received placebo (66.7% vs 36.0%). This meant that 3.3 patients would need to be treated with memantine for one additional patient to benefit.
• Discontinuations owing to adverse events were similar between groups.

IN PRACTICE

"[The study] provides a proof of concept that memantine may be an effective therapeutic for cognitive manifestations of NPSLE [neuropsychiatric SLE]. Larger trials are needed to confirm these results," the authors of the study wrote.

SOURCE

The study was led by Jillian P. Rhoads and Lillian N. Ahmad, Vanderbilt Institute for Clinical and Translational Research, Vanderbilt Health, in Nashville, Tennessee. It was published online on August 21, 2026, in the Annals of the Rheumatic Diseases.

LIMITATIONS

The study was terminated early owing to challenges in recruitment of patients. Researchers could not assess the longer-term effects of memantine or durability of response. The data on the primary outcome were collected only from participants who completed the full 12 weeks of treatment.

DISCLOSURES

The study received funding from the Kleberg Foundation, Evergreen Therapeutics, Inc., and a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences. Three authors reported being inventors on a method-of-use patent related to the trial. One author reported consulting for AstraZeneca and GSK.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.