The limited practice of depot antipsychotics and psychoeducation use, recommended for overcoming the noncompliance of patients with severe mental disorders, is linked to a high incidence of treatment violation. Therefore, the development of personalized mental healthcare approaches is a crucial healthcare task. To describe and differentiate the role of clinical, social and psychological factors that lead to different level of treatment engagement of psychiatric inpatients. Secondary analysis of findings from 91 inpatients, based on the Treatment Motivation Assessment Questionnaire and Medication Compliance Scale, as well as the Scale of Internalized Stigma of Mental Illness and Perceived Discrimination and Devaluation Scale. Factorial analysis, cluster analysis and analysis of variance with p-level=0.05 and the calculation of the effect size (ES) according to Cohen's d and Cramer's V were used. The nature of therapy compliance in various categories of patients is mediated differentially, including: the severity of negative symptoms (ES=0.29), the global level of functioning and work maladjustment (ES=0.23-0.26), various motivational and behavioral styles (ES≥0.74) and the intensity of psychiatric stigmatization (ES≥0.88). Consideration of the clinical, social and psychological factors should empirically determine the strategies for the personalized use of prolonged antipsychotics and socio-psychotherapeutic interventions when developing an individual treatment plan for psychiatric in-patients.