Although there are many antipsychotics, resistant schizophrenia is still to be an extremely important problem in psychiatrists' practice.

Finding a new strategy, different from the ones in daily standardized practice, could give better perspectives for the outcome of the cases of resistant schizophrenia.

Adding memantine for about six months to the last antipsychotic used in the treatment of resistant schizophrenia could be used as a method in order to induce a response to the treatment due to modulation of NMDA receptors.

Two study cases: patients diagnosed with schizophrenia paranoid type, many years ago, with many hospitalisations for psychotic episodes admitted into the hospital for a psychotic relapse. The patients were treated with 2 antipsychotics (each for 8 weeks and adequate dose) without response. Both cases had a common approach from the moment of failure of the second antipsychotic: adding memantine 20 mg per day to the second antipsychotic, maintained with the same dose from that moment.

Adding memantine to the last antipsychotic induced the remission in both cases of resistant schizophrenia. This association was made for a period of 6 months and after that the dose of memantine was progressively reduced in 2 weeks. We kept the antipsychotic as a main treatment. The remission was kept during the period of association and one year after the withdrawal of the memantine.

We think that memantine modulation of NMDA receptors in combination with antipsychotic D2 receptor blockade can improve the response of resistant schizophrenia.