Memantine for the Treatment of Cognitive Dysfunction and Negative Symptoms in Patients With Chronic Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of 24 weeks memantine add-on treatment to risperidone for the treatment of negative symptomatology and cognitive impairment in patients with chronic schizophrenia.

Detailed Description
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This study examines the efficacy and safety of 24 weeks memantine add-on treatment to risperidone for the treatment of negative symptomatology and cognitive impairment in patients with chronic schizophrenia. The trail was double-blind, prospective, randomized, placebo-controlled, parallel-group and consisting of a 'placebo-run-in' period, treatment, and follow-up periods. Study personnel and participants were blinded to group assignment. In the 'run-in' period, patients received Lorazepam for the treatment of anxiety and tension states for two weeks before starting antipsychotic therapy. After the 'run-in' period treatment, patients began receiving antipsychotic therapy with Risperidon with continuous concomitant administration of a 24 weeks Memantine, 20 mg/d, or placebo. Adherence was assessed at each clinic visit by pill count. In cases of anxiety and tension states, an experienced psychiatrist decided whether patients should receive Lorazepam, 5 mg/d, as rescue medication in addition to the study medication (Memantine or placebo), to which the patients remained blinded. In cases of pseudo parkinsonism patients were allowed to receive Biperiden, up to 8 mg/d, and for the treatment of patients suffering from sleep disorders Zopiclon (15 mg/d) was allowed. The consumption of alcohol and drugs were not allowed during the trial. In both study parts, psychiatric assessments were performed at baseline as well as after 2; 4; 6; 12 and 24 weeks after treatment (that is, during the follow-up period). The neuropsychological examination was performed at baseline, and after 6 and 24 weeks. Psychiatric changes, adverse events, laboratory values, dose adjustments of the antipsychotic therapy, and possible pharmacologic adverse effects were systematically monitored throughout the study.

Official Title
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Memantine add-on to Risperidon for Treatment of Negative Symptoms and Cognitive Dysfunction in Patients With Chronic Schizophrenia: Results of a Proof of Concept Study

Conditions
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Chronic Schizophrenia

Intervention / Treatment
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* Drug: Memantine
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia (DSM-IV) Age 18 to 40 Stable negative syndrome (PANSS negative score > 20) At least one previous schizophrenic episode Informed consent Subjects must be considered by the investigator to be compliant with investigations and appointments Subjects must have an educational level and a degree of understanding such that they can meaningfully communicate with the investigator Exclusion Criteria: Axis I disorder other than schizophrenia within 12 months, e.g. schizoaffective disorder Severe positive symptomatology (PANNS positive score > PANNS negative score) Dependency on alcohol or addictive drugs within 6 months of the baseline evaluation Contraindication of risperidone Significant neurological, cardiovascular, hepatic, renal, metabolic, or other medical diseases or any clinically relevant abnormalities in laboratory tests

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Memantine plus Risperidone<br>24 weeks memantine add on treatment to risperidone | Drug: Memantine<br>* Daily dosage of 20 mg Memantine add-on to Risperidone vs. Placebo add-on to Risperidone<br>* Other names: Akatinol;|
| Placebo Comparator: Placebo plus Risperidone<br>24 weeks placebo add on treatment to risperidone | Drug: Placebos<br>* Daily dosage of 20 mg Placebo add-on to Risperidone vs. Memantine add-on to Risperidone<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in PANSS negative subscore between memantine and placebo treatment |  | during trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Memantine, Negative Syndrome, Schizophrenia, Cognitive impairment