Trial reportPsychological medicine2016
Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.
Trial report in Psychological medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.Clinical drug investigation · 2025Pooled it
- Meta-analysis of cognitive functioning in patients with psychotic disorders and obsessive-compulsive symptoms.European archives of psychiatry and clinical neuroscience · 2021Pooled it
- Single-Dose Memantine Improves Cortical Oscillatory Response Dynamics in Patients with Schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Dementia in older adults with schizophrenia: a 12-year analysis of prevalence, incidence, and treatment patterns in South Korea.Schizophrenia (Heidelberg, Germany) · 2025Article
- Add-On Pharmacotherapy in Schizophrenia: Does It Improve Long-Term Outcomes? A Systematic Review.Journal of clinical medicine · 2025Review
- Following the Action of Atypical Antipsychotic Clozapine and Possible Prediction of Treatment Response in Schizophrenia.Life (Basel, Switzerland) · 2025Review
- Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement.Biological psychiatry · 2025Review
- Drugs with glutamate-based mechanisms of action in psychiatry.Pharmacological reports : PR · 2024Review
- Analysis of clinical studies on clozapine from 2012-2022.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Pharmacological Treatments of Negative Symptoms in Schizophrenia-An Update.Journal of clinical medicine · 2024Review
- Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis.EClinicalMedicine · 2024Article
- Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review.Neuropsychopharmacology reports · 2024Review
- Delirium due to Trousseau syndrome treated with memantine and perospirone: A case report.PCN reports : psychiatry and clinical neurosciences · 2023Article
- Unveiling the Enigma: Exploring Risk Factors and Mechanisms for Psychotic Symptoms in Alzheimer's Disease through Electronic Medical Records with Deep Learning Models.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia-A Systematic Review.Journal of clinical medicine · 2023Review
- Glutamatergic dysfunction in Schizophrenia.Translational psychiatry · 2022Review
- A narrative review of treatment interventions to improve cognitive performance in schizophrenia, with an emphasis on at-risk and early course stages.Psychiatry research · 2022Review
- MDMA for the Treatment of Negative Symptoms in Schizophrenia.Journal of clinical medicine · 2022Review
- Memantine for the Treatment of Behavioral Disturbance in Unspecified Major Neurocognitive Disorder.Cureus · 2021Article
- Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety-Particularities in the Context of COVID-19.Brain sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.
methodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.
resultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.
conclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
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Registered trials
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.