Effect of Memantine on ERP in Early Schizophrenia and Healthy Subjects

• Status: Unknown status
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with schizophrenia are deeply affected by the positive symptoms, negative symptoms and cognitive impairment. A generalized cognitive deficit could be frequently observed and traced back to early stage of the disease. Currently medication intervention significantly improves positive symptoms through dopamine receptor modification, leaving alone the negative symptoms and cognitive impairment. Besides dopamine dysregulation, more and more attention had been paid to the association of N-methyl-D-aspartate (NMDA) type glutamate receptor and schizophrenia, focusing on the neurobiological and cognitive biomarkers change. Memantine, an uncompetitive antagonist of NMDA type glutamate receptor approved as cognitive enhancer for Alzheimer's disease, is a potential candidate for preventing cognitive decline of schizophrenia. Previous randomized clinical trials failed to demonstrate its efficacy on chronic schizophrenic patients and it might be related to the chronic and irreversible disease process. There is also study supporting that memantine induces change in mismatch negativity (MMN) in frontal cortex of healthy subjects. This study will compare the MMN change of healthy subjects and the population of early schizophrenia, who has persistent neurobiological, cognitive biomarkers or negative symptoms despite subsided positive symptoms. Both male and female aged 20-45 years old outpatients with a length of illness for less than 5 years since first diagnosed as schizophrenia, currently receiving treatment by atypical antipsychotics in a relatively stable condition will be recruited. Healthy subjects will be recruited comparing their age and sex. We plan to recruit 10 subjects for both patient and healthy subjects with a total of 20 participants. All participants will receive general clinical, cognitive and event-related potential (ERP) evaluation as baseline before taking medication. Twenty mg of memantine will be given 4 hours before ERP retest. The analyses will be performed based on the change of ERP using paired-t sample test. Baseline clinical and cognitive symptoms will be analyzed as possible confounders.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Taiwan University Hospital
• Treatments: Memantine

Criteria

Inclusion criteria for patient subjects:

1. Both male and female outpatients

2. Age 20-45 years old at the time of screening

3. A diagnosis of schizophrenia based on the Structured Clinical Interview for DSM-IV

4. A duration of illness for less than 5 years since initially diagnosed as schizophrenia

5. Currently receiving treatment mainly by an atypical antipsychotic (risperidone, olanzapine, amisulpiride, aripiprazole, quetiapine, ziprasidone, paliperidone), including long-acting injectable antipsychotic

6. A first generation antipsychotic agent only for a low-dose, as needed use purpose

7. No revised use of benzodiazepines, antidepressants, anticholinergics, or other concomitant medications during past 3 months

Inclusion criteria for healthy subjects:

1. Both male and female

2. Age 20-45 years old at the time of screening

3. No psychiatric diagnosis based on the Structured Clinical Interview for DSM-IV

4. No current use of any pharmaceutical agents in past 2 weeks

Exclusion criteria for all participants:

1. A score of 5 or more on any of the 7 positive symptom items of the PANSS rating at screening

2. Scores of 4 on at least 3 of the 7 positive symptom items of the PANSS rating at screening

3. A major relapse resulting in readmission or doubling the dosage of previous effective antipsychotic treatment during the course of illness

4. A change of current antipsychotic medication in recent 3 months

5. Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia

6. A history of pervasive mental disorder or bipolar disorder

7. A medical condition with significant cognitive sequelae

8. A history of substance dependence

9. A history of hypersensitivity to memantine or other drugs of the same class, such as amantadine

10. Pregnancy, plan to get pregnant during the study period, or lactating women

11. Abnormal liver function (AST, ALT higher than doubling the upper limits of normal range) or abnormal renal function (blood creatinine > 1.3 mg/dL)

12. A history of epilepsy

13. A history of myocardial infarction, congestive heart failure, uncontrolled hypertension, stroke, or severe heart block.