The phenomenon of therapeutic resistance in the treatment of schizophrenia: the possibilities of modern diagnostics and methods of anti-resistant effects
Authors: Stanovaya V. V. , Guseynova Z. T. , Ivanov M. V. , Bigday E. V. 
Published: December 2023

The formation of resistance is a key factor in curbing progress in the treatment of schizophrenia. In modern psychiatric practice, despite the emergence of new medical technologies, including the use of a wide arsenal of psychotropic medicinal effects, the frequency of manifestations of therapeutic resistance in the cohort of mentally ill is on average about 30%. The reasons for the formation of resistance identified to date are diverse and can be associated with both biological changes due to violations of the functioning of various neurotransmitter systems. so it is with non-compliance with the regimen of taking medications (drug noncompliance). Therapy-resistant schizophrenia is a serious clinical problem, since patients with such manifestations often feel the need for repeated hospitalizations, have more pronounced violations of social and professional functioning. It has been established that the formation of therapeutic resistance can occur both at the beginning of active treatment and in the process of psychopharmacotherapy. Therefore, it is important to identify predictors of therapeutic resistance, which will allow using methods to overcome it as soon as possible. This literature review examines both the main forms of therapeutic resistance and the features of its formation, as well as the possibilities of drug and non-drug therapy of resistant schizophrenia.

Materials and methods. A literature review was performed in the PubMed database. The keywords types of therapeutic resistance, therapeutically resistant schizophrenia, antipsychotics, methods of anti-resistant effects. Inclusion criteria: randomized and non-randomized clinical trials, meta-analyses and systematic reviews, fulltext articles on therapeutic resistance in mentally ill patients and coping methods. Exclusion criteria: articles of poor quality. Results. The analysis of the literature data has shown the expediency of using not only clozapine, a first-line drug, for therapeutic resistance, but also modern drugs, primarily cariprazine, which, despite limited studies, have shown high efficacy both in combination therapy with clozapine and in monotherapy, in correcting stable productive, negative and cognitive symptoms. The use of augmentation with antidepressants, normotimic and glutamatergic drugs can be used to overcome resistance, but data on the effectiveness of this strategy are ambiguous. Of the non-medicinal methods of treating therapeutically resistant schizophrenia, the use of electroconvulsive therapy is recommended as the only method of biological effects that currently has an evidence base. Conclusions. According to the results of the literature review, the most studied, proven methods of overcoming therapeutically resistant schizophrenia are clozapine and electroconvulsive therapy. At the same time, taking into account the preliminary positive results of the use of third-generation antipsychotics, it can be considered appropriate to use them both in combination therapy and in monotherapy, with insufficient effectiveness of clozapine.