Exploring the "Insight Paradox" in Treatment-Resistant Schizophrenia: Correlations Between Dimensions of Insight and Depressive Symptoms in Patients Receiving Clozapine.

Objective: There remains a lack of clarity as to the possible cross talk of insight into illness and depressive symptoms in treatment-resistant schizophrenia. We therefore set our primary aim to evaluate relationship between insight dimensions and depressive symptoms in patients with treatment-resistant schizophrenia receiving clozapine.

Methods: This was a cross-sectional, non-interventional study, conducted in daily clinical practice conditions. Patients in outpatient clinics between March 2020 and May 2020 with treatment-resistant schizophrenia (based on Treatment Response and Resistance in Psychosis), with no comorbid psychiatric disorder, and with no body mass index greater than 40.0 kg/m were included. We collected sociodemographic variables, scores of insight dimensions (treatment compliance, illness recognition, and symptom relabeling with the Schedule for Assessment of Insight), and depressive symptoms with Calgary Depression Score for Schizophrenia. Linear regression models were used to investigate variables associated with depressive symptoms as the outcome of interest.

Results: The final analysis sample comprised 55 patients with treatment-resistant schizophrenia, with a mean age of 42.48 (SD = 9.18) years and a predominance of the male sex (n = 42, 76.9%). Model 1 [Calgary Depression Score for Schizophrenia ~ (Schedule for Assessment of Insight + Positive and Negative Syndrome Scale)] displayed that 48% of the variation in the Calgary Depression Score for Schizophrenia can be explained by Schedule for Assessment of Insight-composite and Positive and Negative Syndrome Scale-composite ( < .001). More effectively, model 2 [Calgary Depression Score for Schizophrenia ~ (Schedule for Assessment of Insight-illness recognition + Positive and Negative Syndrome Scale-general psychopathology)] revealed that 51% of the variation in the Calgary Depression Score for Schizophrenia can be explained by the sub-scales ( < .001). We further designed a new model in which Global Assessment of Functioning scores were the response variable to explore the link between awareness into illness and functionality (Global Assessment of Functioning ~ Schedule for Assessment of Insight-illness recognition). In this model, awareness of illness did not explain a significant proportion of variance in functionality scores (  = 0.045, (1,52) = 2.48,  = 0.121).

Conclusion: The treatment compliance part of insight was not one of the significant explanatory variables of depressive symptoms, but it explained the variance in functioning, in contrast to the illness recognition dimension of insight. If our findings were replicated in treatment-resistant schizophrenia, they would suggest that promoting treatment compliance dimension of insight instead of recognition of illness could not increase depressive symptoms.