Therapeutic Efficacy and Safety of Memantine for Children and Adults With ADHD With a Focus on Glutamate-Dopamine Regulation: A Systematic Review.

Pharmacotherapy plays a crucial role in treating attention-deficit/ hyperactivity disorder (ADHD). However, current medications for ADHD have limitations and potential adverse effects. Glutamate, a neurotransmitter that directly and indirectly modulates dopamine neurotransmission, is considered a new therapeutic target for ADHD. We conducted a systematic review to determine the efficacy and safety of memantine, an uncompetitive -methyl D-aspartate (NMDA) receptor antagonist, in both pediatric and adult patients with ADHD. We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for articles on memantine use in ADHD patients published up to August 31, 2023, using terms related to ADHD and memantine. Studies selected according to PRISMA guidelines. We included both randomized and nonrandomized trials for a comprehensive review. We excluded non-English publications, review articles, and studies without full text. Two authors extracted data using the data extraction form designed for this review. Independent authors conducted a risk of bias assessment using risk of bias 2 (RoB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I). Six studies met the inclusion criteria, 3 on pediatric populations, and 3 on adults. Three studies were conducted in the United States (2 in adults) and 3 in Iran (1 in adults). Memantine showed potential benefits in managing ADHD symptoms and had a favorable safety profile. However, most studies involved small patient groups at single institutions, and their quality was low. Memantine has the potential to be a relatively safe alternative or adjunctive treatment for ADHD, but more refined studies with larger populations are needed. .