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

62 Participants Needed

Trial Summary

What is the purpose of this trial?

Treatment of schizophrenia currently includes antipsychotic medications and cognitive therapies which improve some symptoms, but do not sufficiently restore cognitive functioning or reduce psychosocial disability. We hypothesize that medications that specifically target sensory information processing deficits, rather than psychotic symptoms per se, will significantly enhance the benefits of a sensory-based targeted cognitive training (TCT) intervention in patients with schizophrenia. We will complete a randomized, double-blind clinical trial to: 1) confirm that the drug memantine augments TCT learning; 2) determine whether memantine enhances the clinical benefits from a full 30 session course of TCT vs. TCT plus placebo in antipsychotic- medicated schizophrenia patients, and 3) determine if memantine's enhancement of TCT is most effective in biomarker-defined subgroups of patients.

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 the drug Memantine effective for improving cognitive symptoms in patients with schizophrenia?

Research shows that Memantine, when added to other treatments, can help improve negative symptoms and cognitive function in patients with schizophrenia. It works by affecting certain brain receptors and has been shown to be safe and effective in several studies. ^{1 2 3 4 5}

Is memantine safe for humans?

Memantine is generally considered safe for humans and is well-tolerated at therapeutic doses. It has been used to treat Alzheimer's disease and has shown to improve symptoms without interfering with normal cognitive functions. ^{1 6 7 8 9}

How does the drug memantine differ from other treatments for schizophrenia?

Memantine is unique because it targets the NMDA receptors in the brain, which are involved in cognitive functions like learning and memory. Unlike other treatments, memantine is specifically noted for improving negative symptoms and cognitive deficits in schizophrenia, making it a promising adjunct therapy. ^{1 2 3 5 10}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

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 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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: a placebo-controlled pilot study. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Germany 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. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. Ireland pubmed.ncbi.nlm.nih.gov

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

6. Spain 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]. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. New Zealand pubmed.ncbi.nlm.nih.gov

Update on the use of memantine in Alzheimer's disease. [2021]

10. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy of Memantine in Schizophrenic Patients: A Systematic Review. [2020]