Abstract
Introduction
. Treatment-resistant schizophrenia remains one of the most challenging problems in contemporary psychiatry and requires the search for additional therapeutic approaches, particularly when the response to adequate antipsychotic treatment, including clozapine, is insufficient. Disturbances of energy metabolism, insulin resistance, and altered insulin signaling in the central nervous system may be among the factors influencing the severity of negative, cognitive, and affective symptoms.
Objective
: to present a series of clinical observations of patients with treatment-resistant schizophrenia in whom the use of insulin and insulin-sensitizing interventions as part of complex therapy was associated with improvement in mental state and everyday functioning.
Materials and Methods
. Three clinical cases of patients with treatment-resistant schizophrenia were analyzed. All patients received standard psychopharmacotherapy together with additional interventions aimed at modulating insulin signaling. In the first case, the patient underwent a course of forced insulin coma therapy, followed by treatment with clozapine and metformin. In the second case, a patient with a partial response to clozapine received metformin, a combination of alogliptin and pioglitazone, fenofibrate; subsequently alogliptin/pioglitazone was changed to canagliflozin. In the third case, high-dose insulin euglycemic therapy was administered in a toxicological intensive care unit after a suicide attempt and severe poisoning with clozapine and amitriptyline. The dynamics of psychopathological symptoms, emotional reactivity, cognitive productivity, social activity, everyday functioning, and tolerability of the interventions were assessed.
Results
. In all three cases, metabolic modulation was associated with clinically meaningful improvement. A reduction in negative and affective-motivational symptoms, increased emotional engagement, improved cognitive functioning, greater social activity, and better everyday adaptation were observed. In several cases, subsequent antipsychotic therapy produced a more pronounced clinical effect than at previous stages of treatment.
Conclusions
. The presented observations suggest that disturbances of insulin signaling may be involved in the development of treatment resistance in schizophrenia, and that their correction may be considered a promising direction for adjunctive therapy. These findings require cautious interpretation and do not allow definitive conclusions regarding the efficacy of individual interventions; however, they emphasize the clinical importance of personalized assessment of metabolic status in patients with treatment-resistant schizophrenia.