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

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

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.

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.

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