Critics on "Adjunctive Memantine Therapy for Cognitive Impairment in Chronic Schizophrenia: A Placebo-Controlled Pilot Study"

Abstract

Purpose: Cognitive impairment represents a core feature of schizophrenia among the majority of patients. Cognitive deficits appear during the initial episode of the illness and may appear even in those who are antipsychotic-naive, suggesting that these deficits do not reflect the deteriorative effects of treatment. Because cognitive impairment is among the strongest predictors of functional outcome in patients with schizophrenia, the improvement of cognitive functioning has been identified as an important treatment goal. In this study, we investigated the effect of memantine on cognitive impairment in patients with chronic schizophrenia to study the effects of N-methyl-d-aspartate (NMDA) receptor antagonists. Methods: A 12-week, double-blind, placebo-controlled trial of memantine as an add-on treatment to conventional antipsychotic drugs was conducted among 26 patients with chronic schizophrenia. The subjects were evaluated using the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Symptom Scale (PANSS), the 17-item Hamilton Rating Scale for Depression (HAM-D) A battery of neuropsychological tests was administered to evaluate changes in several domains of cognitive functioning. The K-MMSE, the Hopkins Verbal Learning Test (HVLT), the Rey Complex Figure Test (RCFT), the Digit Span Forward and Backward Test, the Digit Symbol Substitution Test (DSST), the Stroop test, the Trail Making Test (Part A), the Verbal Fluency Test (VFT), and the Boston Naming Test were used to assess attention, auditory and visual memory, and executive functioning. Results: Twenty-nine subjects met the eligibility criteria at baseline. However, three subjects withdrew their consent after random assignment. The remaining 26 subjects were randomly assigned to memantine (n = 15) or placebo (n = 11) treatment groups and completed the 12-week trial. Compared to the placebo condition, memantine treatment was not associated with significantly improved scores on the cognitive measures. Among the domains of cognitive functioning assessed by this study, memantine was associated with improved immediate and delayed recall, as measured by the Hopkins Verbal Learning Test (HVLT); selective attention, as measured by the Stroop Test; overall scores on the Trail Making Test, Part A; and overall scores on the Boston Naming Test. The scores on the PANSS negative subscale improved more in the memantine group than in the placebo group but did not change significantly. Memantine was well tolerated and the incidence of adverse events was similar between groups. In total, 47% of the memantine group and 55% of the placebo group experienced adverse events. Conclusion: The addition of memantine to the treatment of patients with schizophrenia did not improve their cognitive functioning or affect their psychopathology. Memantine showed good tolerability and did not exacerbate positive symptoms among the patients with chronic schizophrenia who participated in this study. However, future studies are required to examine more deeply the effects of memantine on cognitive impairment in schizophrenia.