Approaches for the treatment of people with schizophrenia that does not respond to clozapineor ultra-resistant schizophrenia. Review of the evidence

Abstract

30% of people with schizophrenia do not respond to antipsychotics. In these cases, treatment with clozapine is indicated, but only 40% of this subpopulation responds to treatment, thus forming a subgroup of resistant patients who do not respond to clozapine and are therefore referred to as ultra-resistant. Between 12 and 20% of people with schizophrenia are ultra-resistant. The objective of this work is to review the possible treatment for ultra-resistance and its scientific evidence. From the review carried out, it is clear that: 1) The addition of a second antipsychotic to clozapine has a partial response, and there is no antipsychotic that shows significant difference compared to others. 2) Of the antiepileptics, the one that generates a slight clinical improvement is sodium valproate, but even so, a complete response is not achieved. Lamotrigine, in turn, generates a therapeutic response in studies with mild to moderately symptomatic patients. 3) The use of inhibitors of d-amino oxidase, such as sodium benzoate, only achieved a slight clinical improvement without achieving a comprehensive therapeutic response. 4) The addition of memantine was not effective. 5) The addition of electroconvulsive therapy generates significant therapeutic response in severely symptomatic patients for both the positive and negative symptomatic dimensions. Electroconvulsive therapy does not generate cognitive alterations, produces improvement in immediate and long- erm verbal memory and in executive functions. Currently more robust evidence concerning therapeutic approaches to ultrarresistant schizophrenia are lacking. In particular, randomized and controlled studies with significant number of patients will be valuable of help to make decisions in this subpopulation with an important impairment in their functionality and quality of life.