Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: A preliminary study

Background: Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits. Methods: Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. Results: We found a significant improvement of the PANSS score (baseline 116.28 ± 21.9 vs. 97.86 ±24.48 after six weeks, t = 5.98, p < 0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40 ± 6.38 vs. 31.71 ± 7.76 after six weeks, t = 5.87, p < 0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement. Conclusion: Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations.