EXAMINING LURASIDONE EFFICACY IN SCHIZOPHRENIC PATIENTS WITH COMORBID ALCOHOL AND SUBSTANCE USE DISORDER: A MULTICENTRIC PROSPECTIVE INVESTIGATION

Abstract Background Alcohol/Substance Use Disorder (AUD/SUD) among schizophrenic patient represent a common and problematic co-occurrence, with a rate of comorbidity assessed between 40% and 70%, especially in young patients at the onset of their disorder (1-2). Comorbid patients are usually difficult to treat: they show a very low level of compliance, and are frequently exposed to drop-out and lack of efficacy for the available antipsychotic drugs leading to worsened clinical outcomes and increased difficulty in treatment (3-4). Aims & Objectives to evaluate the effectiveness and safety of the second generation antipsychotic lurasidone in schizophrenic patients comorbid AUD/SUD. Method In this prospective, multicentric, real-world study, a total of 21 patients (M/F ratio: 14/7; age=34.20 ± 11.81), diagnosed with Schizophrenia and AUD/SUD (6 and 15, respectively) were recruited and treated using lurasidone up to 148mg/day. Evaluations were performed at the baseline (T0) and after 4 weeks (T1) using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Improvement (CGI-I) scores. Quality of life (Q-LES-Q-SF), alcohol and substance related aggressiveness (Modified Overt Aggression Scale/MOAS), as well as craving for substances (VAS) were assessed. Repeated-measures ANOVA (rm-ANOVA) models were used to estimate the effect of treatment on the aforementioned psychometric scales. Results Lurasidone was effective in reducing the total burden of psychopathology, as highlighted by the significant reduction of PANSS (F12,1= 8.422; P= 0.013), CGI-S (F11,1= 30.94; P<0.001), MOAS (F12,1= 5.691; P=0.034) total scores. Furthermore, we found a significant reduction of craving intensity/VAS for craving from baseline to T1 (F12,1= 7.112; P= 0.021). The overall impact of Lurasidone has resulted in a significant enhancement of quality of life (Q-LES-Q-SF: F11,1= 5.273; P= 0.042). However, we observed a substantial non-adherence rate to the treatments, with 38% (8 out of 21) of patients discontinuing prior to T1. Among these, 9.5% (2 patients) relapsed into substance use, 9.5% (2 patients) experienced significant side effects, and 19% (4 patients) dropped out for reasons that remain unidentified. Discussion & Conclusion These preliminary findings underscore the potential utility of Lurasidone for dual disorder patients, targeting not only symptoms within the psychotic spectrum but also behaviours tied to substance and alcohol consumption. The observed high attrition rate is likely due to the inherent nature of the study (outpatients setting, involving subjects with severe dual diagnoses). Overall, pharmacological treatments of dual diagnosis are complex and require personalized approaches considering the heterogeneity of the population. Future research should focus on developing individualized treatment plans and understanding the biological underpinnings of dual diagnosis to create more targeted, effective pharmacological interventions. References [1]Somers, J. M., Moniruzzaman, A., Rezansoff, S. N., Brink, J., &Russolillo, A. (2016). The prevalence and geographic distribution of complex co-occurring disorders: a population study. Epidemiology and psychiatric sciences, 25(3), 267–277. https://doi.org/10.1017/S2045796015000347 [2]Alsuhaibani, R., Smith, D. C., Lowrie, R., Aljhani, S., &Paudyal, V. (2021). Scope, quality and inclusivity of international clinical guidelines on mental health and substance abuse in relation to dual diagnosis, social and community outcomes: a systematic review. BMC psychiatry, 21(1), 209. https://doi.org/10.1186/s12888-021-03188-0 [3]Schä fer I, Fischer M, Reimer J, Karow A, Haasen C. Significance of psychiatric comorbidity for the outcome of maintenance treatment – a review of the literature. Ment Health Subst Use 2011, 4(1): 62- 71, doi: 10.1080/17523281.2011.533452. [4]Martinotti, G., Chiappini, S., Mosca, A., Miuli, A., Santovito, M. C., Pettorruso, M., Skryabin, V., Sensi, S. L., &Giannantonio, M. D. (2022). Atypical Antipsychotic Drugs in Dual Disorders: Current Evidence for Clinical Practice. Current pharmaceutical design, 28(27), 2241–2259. https://doi.org/10.2174/1381612828666220623092853