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.

Abstract

Introduction: Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia.

Materials and methods: Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks.

Results: Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group.

Discussions: Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Attention / drug effects
  • Chronic Disease
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Memantine / administration & dosage
  • Memantine / adverse effects
  • Memantine / therapeutic use*
  • Memory / drug effects
  • Problem Solving / drug effects
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Risperidone / administration & dosage
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Socioeconomic Factors
  • Verbal Learning / drug effects
  • Young Adult

Substances

  • Antipsychotic Agents
  • Risperidone
  • Memantine

Associated data

  • ClinicalTrials.gov/NCT00148590
  • ClinicalTrials.gov/NCT00148616