Evidence map›Paper›PMID 40748569›Full record

SynthesisClinical drug investigation2025

Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.

Houlin Hong, Jack Donlon, Martin Schaefer, Susanne Sarkar, Dragana Bugarski-Kirola, Mujeeb U Shad, Wei Hou, Matthias Kirschner, Sajoy P Varghese, Ludmil Mitrev and 9 more

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Clinical drug investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Houlin HongCenter for Systems and Community Design, CUNY School of Public Health and Health Policy, New York City, NY, USA.
Jack DonlonCooper Medical School of Rowan University, Camden, NJ, USA.
Martin SchaeferDepartment of Psychiatry, Psychotherapy, Psychosomatics, and Addiction Medicine, Evang Kliniken Essen-Mitte, Essen, Germany.
Susanne SarkarDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Dragana Bugarski-KirolaAcadia Pharmaceuticals, Luzern, Switzerland.
Mujeeb U ShadDepartment of Psychiatry, University of Nevada, Las Vegas, NV, USA.
Wei HouDepartment of Family, Population and Preventive Medicine, School of Medicine, Stony Brook University, Stony Brook, NY, USA.
Matthias KirschnerDivision of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
Sajoy P VargheseVISN 23, Clinical Resource Hub, Minneapolis VA Medical Center, Minneapolis, MN, USA.
Ludmil MitrevDivision of Cardiothoracic Anesthesiology, Department of Anesthesiology, Cooper University Healthcare, Cooper Medical School of Rowan University, Camden, NJ, USA.
Valentina EcheverriaFacultad de Medicina y Ciencias, Universidad San Sebastián, Lientur, 1457, Concepción, Chile.
John DibatoCooper Research Institute, Cooper Medical School of Rowan University, Camden, NJ, USA.
Selene R T VeermanCommunity Mental Health, Mental Health Service Noord-Holland Noord, Alkmaar, The Netherlands.
Rohit AiyerSunny Hills Behavioral Health, Fullerton, CA, USA.
Thomas N FerraroDepartment of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
Gerardo VillarrealDepartment of Psychiatry and Neuroscience, New Mexico Veterans Affairs Healthcare System, University of New Mexico, Albuquerque, NM, USA.
Shafiqur RahmanDepartment of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD, USA.
Trevor W StoneNuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.
Maju M KoolaMental Health and Behavioral Services, Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA. majumkoola@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMemantine is an N-methyl-D-aspartate (NMDA) receptor antagonist with favorable safety and side effect profiles. There is a growing body of evidence for memantine as an adjunctive therapy for the positive, negative, and cognitive symptoms of schizophrenia.

objectiveThis meta-analysis examined the efficacy of memantine as an add-on to treatment with antipsychotic(s) for the primary negative symptoms (PNS) of schizophrenia.

methodsWe followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched for relevant publications in PubMed, Cochrane Library, PsycINFO, Embase, and China Journal Net databases from inception using the following search terms: memantine, schizophrenia, randomized controlled trials (RCTs), RCT, and clinical trial. Searches were limited to English- and Chinese-language articles to date. Standardized mean differences (SMDs) with 95% confidence intervals were calculated using RevMan 5.4 to assess the effect size. Risk of bias was assessed using RoB 2.0.

resultsIn total, 13 RCTs were identified (N = 681). Memantine was superior to placebo in treating negative symptoms, with an SMD of 0.79 (p = 0.0001, N = 631, 12 RCTs). Analysis of three studies whose corresponding authors provided original datasets showed an SMD of 2.16 (p = 0.25, N = 97) after adjusting for change in psychosis, depression, and extrapyramidal symptoms, suggesting that memantine is efficacious in treating PNS. Additionally, cognitive testing significantly improved, with an SMD of 0.66 (p = 0.0001, N = 395, eight RCTs). Positive symptoms were not significantly improved (SMD = 0.24, p = 0.1, N = 631, 12 RCTs).

conclusionsTo our knowledge, this is the first study showing a large effect size for treating PNS with memantine. Although statistical significance was not reached because of the small sample size (N = 97), the results were as expected because drugs such as memantine that act at NMDA receptors are unlikely to be effective as stand-alone treatments. Future RCTs should evaluate NMDAergic drugs in combination with complementary medications to optimize therapeutic effects for all three domains of schizophrenia psychopathology.

Indexed as

Excitatory Amino Acid AntagonistsMemantineSchizophreniaAntipsychotic AgentsDrug Therapy, CombinationHumansRandomized Controlled Trials as TopicTreatment OutcomeAntipsychotic AgentsExcitatory Amino Acid AntagonistsMemantine

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.