Clinical trial NCT00148616: Memantine for the Treatment of Cognitive Dysfunction and Negative Symptoms in Patients With Chronic Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Schizophrenia
Keywords: Memantine
Negative Syndrome
Schizophrenia
Cognitive impairment
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2005-09-08
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in PANSS negative subscore between memantine and placebo treatment
timeFrame: during trial
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin; Campus Charité Mitte; Dept. for Psychiatry and Psychotherapy
Study officials:
affiliation: Charite Campus Mitte; Dept. of Psychiatry and Psychotherapy and Department of Psychiatry, Kliniken Essen-Mitte, Essen
name: Martin Schaefer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schaefer M, Sarkar S, Theophil I, Leopold K, Heinz A, Gallinat J. Acute and Long-term Memantine Add-on Treatment to Risperidone Improves Cognitive Dysfunction in Patients with Acute and Chronic Schizophrenia. Pharmacopsychiatry. 2020 Jan;53(1):21-29. doi: 10.1055/a-0970-9310. Epub 2019 Aug 7.