Memantine for Cognitive Improvement in Schizophrenia

Overseen By Gregory A Light, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of California, San Diego

Must be taking: Antipsychotics

Disqualifiers: Substance abuse, Brain injury, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether memantine can improve cognitive function in people with schizophrenia when combined with cognitive training. While schizophrenia treatments often focus on reducing symptoms, this trial aims to enhance thinking and processing skills. Participants will receive either memantine or a placebo while undergoing targeted cognitive training. This trial may suit those diagnosed with schizophrenia or schizoaffective disorder who struggle with clear thinking and managing daily tasks. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in schizophrenia care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants are already on antipsychotic medications. It seems likely that you can continue your current antipsychotic treatment while participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that memantine has been studied for safety in treating Alzheimer's disease. In these studies, most patients tolerated memantine well. Common side effects were mild and included dizziness, headache, and constipation. Although these studies focused on Alzheimer's, they offer some insight into the drug's safety for other uses.

Researchers are examining memantine for improving thinking and memory in people with schizophrenia. One study found that memantine did not significantly enhance these functions in schizophrenia, but it did not introduce any new safety concerns. The FDA has approved memantine for Alzheimer's disease, indicating its safety for use in people. However, individual responses vary, so discussing potential risks with healthcare professionals is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Unlike the standard treatments for schizophrenia, which often target dopamine pathways, memantine offers a fresh approach by acting on the brain's NMDA receptors. This mechanism may help improve cognitive functions like memory and learning, areas often left unaddressed by traditional antipsychotic medications. Researchers are particularly excited about memantine's potential to enhance cognitive training performance, offering a dual approach to tackle both symptoms and cognitive deficits in schizophrenia.

What evidence suggests that memantine could be an effective treatment for cognitive improvement in schizophrenia?

Research shows that memantine might improve thinking skills in people with schizophrenia. Some studies have found that memantine can enhance cognitive functions related to thinking and understanding. In this trial, participants will join different treatment arms to assess its effectiveness. One group will receive memantine alongside targeted cognitive training to evaluate whether memantine enhances cognitive training performance. Another group will receive a placebo with the same cognitive training. While memantine mainly helps with negative symptoms like lack of motivation or social withdrawal, its potential to improve thinking skills is promising. Memantine is also known for aiding memory and thinking problems in Alzheimer's disease, suggesting it might offer similar benefits for schizophrenia. Although results are mixed, these findings give hope that memantine could boost the effects of cognitive training for patients. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with schizophrenia or schizoaffective disorder, who can understand and communicate in English. They must not have dementia, mental retardation, current drug abuse issues, severe sensory impairments, traumatic brain injury, or be pregnant.

Inclusion Criteria

Age 18-65

Written informed consent to participate in the study

Absence of dementia or mental retardation

Exclusion Criteria

Under conservatorship (determined by Anasazi)

You cannot participate in the study if you have significant hearing or vision problems.

You are pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive memantine or placebo and complete 30 sessions of targeted cognitive training

13 weeks

30 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular assessments (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Memantine
• Placebo

Trial Overview The study tests if Memantine can boost the effects of targeted cognitive training (TCT) in improving cognitive functions in schizophrenia patients. Participants will either receive Memantine or a placebo alongside TCT sessions and are randomly assigned to these groups.

How Is the Trial Designed?

Group I: TCT + MEM Active Control 1 Intervention

Subjects will be assigned to take memantine and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Group II: TCT + PBO Placebo Group 1 Intervention

Subjects will be assigned to take placebo and will complete 30 hours of targeted cognitive training in order to assess whether memantine enhances cognitive training performance

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

In a study involving 52 clozapine-treated patients with refractory schizophrenia, adding memantine for 12 weeks significantly improved memory and negative symptoms compared to placebo, with effect sizes of 0.30 and 0.29 respectively.

The addition of memantine was associated with only mild and transient side effects, suggesting it is a safe option for enhancing treatment in patients with treatment-resistant schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study. Veerman, SR., Schulte, PF., Smith, JD., et al.[2022]

In a phase II double-blind trial involving 30 elderly patients, memantine significantly improved vigilance, short-term memory, and concentration compared to a placebo.

Memantine was well-tolerated with good safety profiles, and it showed beneficial effects on psychiatric and neurological symptoms, suggesting its potential for further investigation in a phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of impaired cerebral function in psychogeriatric patients with memantine--results of a phase II double-blind study. Ambrozi, L., Danielczyk, W.[2013]

Memantine, an NMDAR antagonist, shows promise as an add-on therapy for schizophrenia, particularly in improving negative symptoms, based on a systematic review of clinical data.

While memantine appears effective for negative symptoms, it does not significantly improve positive or cognitive symptoms in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Memantine in Schizophrenic Patients: A Systematic Review. Di Iorio, G., Baroni, G., Lorusso, M., et al.[2020]

Memantine is a unique NMDA receptor antagonist that selectively blocks harmful glutamate activity associated with Alzheimer's disease while preserving normal cognitive function, making it a promising treatment option.

Clinical studies have shown that memantine improves symptoms and slows clinical deterioration in patients with moderate-to-severe Alzheimer's disease, leading to its approval in the US in 2003.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of memantine for the treatment of Alzheimer's disease. Ferris, SH.[2019]

In patients with moderate to severe Alzheimer's disease, memantine showed a statistically significant but clinically small positive effect on cognition and daily functioning in three out of four randomized controlled trials, indicating it may help improve some symptoms in this population.

For patients with mild to moderate Alzheimer's disease, the addition of memantine to donepezil demonstrated positive effects on cognition and daily living activities, suggesting it could be beneficial when used in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of memantine in Alzheimer's disease. van Marum, RJ.[2021]

Memantine, an NMDA receptor antagonist approved for Alzheimer's disease, has shown promise as an adjunctive treatment for schizophrenia, improving negative and cognitive symptoms based on multiple randomized clinical trials.

Unlike other NMDA antagonists, memantine has a favorable safety profile, potentially due to its unique mechanism of action as a low-affinity, fast off-rate antagonist that preferentially inhibits extrasynaptic NMDA receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Memantine Effective as an NMDA-Receptor Antagonist in Adjunctive Therapy for Schizophrenia? Kikuchi, T.[2023]

In a study involving 46 adult male patients with schizophrenia, adding 20mg of memantine to risperidone significantly improved negative symptoms and cognitive function after 12 weeks of treatment.

While there were no significant differences in positive symptoms or general psychopathology between the memantine and placebo groups, the results support memantine as an effective adjunct treatment for enhancing certain aspects of schizophrenia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of memantine added to risperidone on the symptoms of schizophrenia: A randomized double-blind, placebo-controlled clinical trial. Mazinani, R., Nejati, S., Khodaei, M.[2022]

In a proof-of-concept study involving 24 patients with schizophrenia, memantine added to risperidone treatment significantly improved cognitive functions such as attention, problem-solving, verbal learning, and flexibility in those with acute schizophrenia.

Patients with chronic schizophrenia also benefited from memantine, showing better immediate memory and a greater reduction in negative symptoms compared to those receiving a placebo, suggesting potential neuroprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and Long-term Memantine Add-on Treatment to Risperidone Improves Cognitive Dysfunction in Patients with Acute and Chronic Schizophrenia. Schaefer, M., Sarkar, S., Theophil, I., et al.[2020]

Memantine is an effective treatment for moderate-to-severe Alzheimer's disease, acting as a neuroprotective agent by blocking excessive calcium influx through NMDA receptors, which helps maintain normal brain signaling.

While memantine does not cure or reverse Alzheimer's disease, it can enhance cognitive function and is safe to use in combination with other treatments, as supported by various clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Glutamate-related excitotoxicity neuroprotection with memantine, an uncompetitive antagonist of NMDA-glutamate receptor, in Alzheimer's disease and vascular dementia]. Tanović, A., Alfaro, V.[2013]

In a 12-week study involving 26 patients with chronic schizophrenia, memantine did not significantly improve cognitive function compared to a placebo, indicating limited efficacy as an adjunctive treatment.

While memantine did not enhance cognitive performance, it was well-tolerated and did not worsen positive symptoms of schizophrenia, suggesting it may be safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: a placebo-controlled pilot study. Lee, JG., Lee, SW., Lee, BJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5294374/

Efficacy of Memantine in Schizophrenic Patients Memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve ...

2. nature.com nature.com/articles/s41537-018-0064-6

Efficacy of different types of cognitive enhancers for ... This meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0028390823003271

Memantine: Updating a rare success story in pro-cognitive ... Considered one of the rare exceptions, memantine has consistently demonstrated restorative and prophylactic properties in many AD models.

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2018.00091/full

Medications Used for Cognitive Enhancement in Patients ... ... efficacy of memantine on cognitive impairment in patients with schizophrenia. ... This clinical trial showed that memantine appeared to be effective on cognition.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02240589?term=AREA%5BBasicSearch%5D(bvmt)&rank=7

Memantine for Neuroprotection and Cognitive ... The purpose of this study is to determine if memantine can improve cognitive and neuropsychiatric outcomes after severe traumatic brain injury. Detailed ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2762361/

Memantine: a review of studies into its safety and efficacy in ... This review covers key studies of memantine's safety and efficacy in treating moderate to severe AD. It also covers current research into other dementias.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00097942

Evaluation of the Safety and Efficacy of Memantine ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

8. ema.europa.eu ema.europa.eu/en/documents/scientific-discussion-variation/axura-h-c-378-ii-11-epar-scientific-discussion-variation_en.pdf

Axura, INN-Memantine The safety evaluation of memantine in the treatment of mild to severe AD was based on data from six. 6-month, placebo-controlled clinical studies, one 3-month, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3372565/

Adjunctive Memantine Therapy for Cognitive Impairment in ... Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study.