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Efficacy of cariprazine on predominant negative symptoms of patients with schizophrenia: post hoc analysis of PANSS data, Marder factors, and cognition
S550
P.3.d. Psychotic disorders and treatment − Treatment (clinical)
Results: The majority of patients were discharged from hospital with second-generation antipsychotics: 115 (65.7%) patients with LAI second-generation antipsychotics and 141 (80.6%) with second generation oral antipsychotics. The minority of patients were discharged from hospital with first generation antipsychotics: 35 (57.4%) with LAI, and 53 (86.9%) with first generation oral antipsychotics. Sixty-three (33.7%) patients were treated with monotherapy, 119 (63.6%) with combination of two antipsychotics and 5 (2.7%) with combination of three antipsychotics. Sixty-six (35.3%) patients had clozapine in prescriptions throughout the treatment, but it was combined with other drugs for psychosis in the majority of cases. Drugs were generally prescribed in their recommended doses, with clozapine being prescribed at the lower end of its therapeutic range. 95% of patients received psychiatric co-medications such as anxiolytics or antidepressants. Rehospitalization rate during the first 12 months was 36.4% (95% CI 29.5–43.1). The main reason for the hospital readmission was relapse in 38 (57.6%) patients (95% CI 45.9–68.6), followed by non-compliance in 15 (22.7%) patients (95% CI 13.3–32.9), social reasons in 5 (7.6%) patients (95% CI 1.8–14.5), side effects in 4 (6.1%) patients (95% CI 45 1.4–12.1), and suicide attempt in 1 (1.5%) patient (95% CI 0.0–10.3). Conclusion: Use of oral and LAI second-generation antipsychotics in Psychiatric Hospital “Sveti Ivan” is extensive. More than half of the patients participating in this study were on a LAI. Contrary to recommendations in the literature, combination of two drugs for psychosis was the most common pattern of use, while the prescription frequency for antipsychotic monotherapy was low. Also, most patients received psychiatric co-medications such as anxiolytics or antidepressants. Rehospitalization rate during the first 12 months was similar to those reported in literature [1]. The findings of this study contribute to mapping of the use of drugs for psychosis and therefore may improve treatment outcomes. References [1] Kishimoto T, Robenzadeh A, Leucht C, et al., 2014. Long-Acting Injectable vs Oral Antipsychotics for Relapse Prevention in Schizophrenia: A Meta-Analysis of Randomized Trials. Schizophrenia Bulletin. 40(1): 192–213. doi, 10.1093/schbul/sbs150.
P.3.d.036 Efficacy of cariprazine on predominant negative symptoms of patients with schizophrenia: post hoc analysis of PANSS data, Marder factors, and cognition S. Marder1 , I. Laszlovszky2 ° , E. Szalai2 , B. Szatm´ari2 , J. Hars´anyi2 , A. Barab´assy2 , M. Debelle3 , S. Durgam4 , I. Bitter5 , G. N´emeth2 1 Semel Institute at UCLA, Section on Psychosis, Los Angeles, USA; 2 Gedeon Richter Plc., Medical Division, Budapest, Hungary; 3 Gedeon Richter Plc- at the time of the study, Medical Division, Budapest, Hungary; 4 Forest Research Institute- an Allergan affiliate, Clinical Development, Jersey City, USA; 5 Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary Introduction: Schizophrenia is a complex disorder characterized by positive and negative symptoms, and cognitive impairment. Cariprazine, a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is FDA approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adult patients. In a Phase III, 26-week double-blind, randomized, active-controlled trial, cariprazine was significantly more effective than risperidone in
treating negative symptoms and improving function in patients with prospectively identified predominant negative symptoms of schizophrenia. Aims of the study: Data derived from the Positive and Negative Syndrome Scale (PANSS) were evaluated in the primary analysis; post hoc analyses of additional PANSS data from this positive study were conducted to further elucidate the effects of cariprazine in the treatment of predominant negative symptoms of schizophrenia. Methods: Subjects with schizophrenia and PANSS factor score for negative symptoms (PANSS-FSNS) 24 with no pseudospecific factors (eg, extrapyramidal and depressive symptoms) were randomized to cariprazine 4.5 mg/d (dose range: 3−6 mg/d) or risperidone 4 mg/d (dose range: 3−6 mg/d) for 26 weeks of doubleblind treatment. The primary efficacy parameter was change from baseline (CfB) to endpoint in PANSS factor score for negative symptoms (PANSS-FSNS) in the intent-to-treat (ITT) population. The secondary efficacy parameter was CfB to endpoint in Personal and Social Performance Scale (PSP), which measured functional improvement. The CfB to endpoint in PANSS factor score for positive symptoms (PANSS-FSPS) was an additional efficacy parameter. Post hoc analyses evaluated CfB in PANSS single items, the PANSS-derived Marder factors (disorganized thought, uncontrolled hostility/excitement, anxiety/depression) [1], and a modified PANSS-based cognitive subscale (items P2, N5, N7, G10, G11) [2]. Results: A total of 461 patients were randomized (1:1) to double-blind treatment; there were 227 cariprazine- and 229 risperidone-treated patients in the ITT population. The least squares mean difference (LSMD) in CfB at Week 26 was statistically significant in favor of cariprazine versus risperidone in PANSS-FSNS (LSMD = −1.46; P = 0.002) and PSP total scores (LSMD = 4.63; P < 0.001). Statistical improvement in favor of cariprazine versus risperidone was seen on the PSP subdomains of self-care (P = 0.004), socially useful activities (P < 0.001), and personal and social relationships (P < 0.001). PANSS-FSPS were low at baseline indicating low levels of positive symptoms in both groups; LS mean CfB was small and similar for cariprazine and risperidone (−1.07 and −1.08, respectively; LSMD = 0.01 [-0.43, 0.45]; P = 0.963). On the PANSS Marder factors, CfB at Week 26 in disorganized thought was on the level of significance in favor of cariprazine (LSMD = −0.63; P = 0.05); changes in the anxiety/ depression and uncontrolled hostility/excitement factors were not statistically different between groups. Significant improvement at Week 26 in favor of cariprazine was seen on the PANSS-based cognitive subscale (LSMD = −0.53; P = 0.028). Conclusion: Statistically significant improvement in negative symptoms and patient function was seen after 26 weeks of monotherapy with cariprazine compared with risperidone in patients with predominant negative symptoms of schizophrenia. Statistically significant improvement was seen in cognitive improvement for cariprazine versus risperidone. References [1] Marder, S.R., Davis, J.M., Chouinard, G. 1997. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry 58, 538–546. [2] Meltzer, H.Y., Cucchiaro, J., Silva, R. 2011. Lurasidone in the treatment of schizophrenia: A randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry 168, 957–967. Disclosure statement: This study is supported by funding from Gedeon Richter, Plc. I, Istv´an Laszlovszky, am an employee of Gedeon Richter Plc.
P.3.d. Psychotic disorders and treatment − Treatment (clinical)
Results: The majority of patients were discharged from hospital with second-generation antipsychotics: 115 (65.7%) patients with LAI second-generation antipsychotics and 141 (80.6%) with second generation oral antipsychotics. The minority of patients were discharged from hospital with first generation antipsychotics: 35 (57.4%) with LAI, and 53 (86.9%) with first generation oral antipsychotics. Sixty-three (33.7%) patients were treated with monotherapy, 119 (63.6%) with combination of two antipsychotics and 5 (2.7%) with combination of three antipsychotics. Sixty-six (35.3%) patients had clozapine in prescriptions throughout the treatment, but it was combined with other drugs for psychosis in the majority of cases. Drugs were generally prescribed in their recommended doses, with clozapine being prescribed at the lower end of its therapeutic range. 95% of patients received psychiatric co-medications such as anxiolytics or antidepressants. Rehospitalization rate during the first 12 months was 36.4% (95% CI 29.5–43.1). The main reason for the hospital readmission was relapse in 38 (57.6%) patients (95% CI 45.9–68.6), followed by non-compliance in 15 (22.7%) patients (95% CI 13.3–32.9), social reasons in 5 (7.6%) patients (95% CI 1.8–14.5), side effects in 4 (6.1%) patients (95% CI 45 1.4–12.1), and suicide attempt in 1 (1.5%) patient (95% CI 0.0–10.3). Conclusion: Use of oral and LAI second-generation antipsychotics in Psychiatric Hospital “Sveti Ivan” is extensive. More than half of the patients participating in this study were on a LAI. Contrary to recommendations in the literature, combination of two drugs for psychosis was the most common pattern of use, while the prescription frequency for antipsychotic monotherapy was low. Also, most patients received psychiatric co-medications such as anxiolytics or antidepressants. Rehospitalization rate during the first 12 months was similar to those reported in literature [1]. The findings of this study contribute to mapping of the use of drugs for psychosis and therefore may improve treatment outcomes. References [1] Kishimoto T, Robenzadeh A, Leucht C, et al., 2014. Long-Acting Injectable vs Oral Antipsychotics for Relapse Prevention in Schizophrenia: A Meta-Analysis of Randomized Trials. Schizophrenia Bulletin. 40(1): 192–213. doi, 10.1093/schbul/sbs150.
P.3.d.036 Efficacy of cariprazine on predominant negative symptoms of patients with schizophrenia: post hoc analysis of PANSS data, Marder factors, and cognition S. Marder1 , I. Laszlovszky2 ° , E. Szalai2 , B. Szatm´ari2 , J. Hars´anyi2 , A. Barab´assy2 , M. Debelle3 , S. Durgam4 , I. Bitter5 , G. N´emeth2 1 Semel Institute at UCLA, Section on Psychosis, Los Angeles, USA; 2 Gedeon Richter Plc., Medical Division, Budapest, Hungary; 3 Gedeon Richter Plc- at the time of the study, Medical Division, Budapest, Hungary; 4 Forest Research Institute- an Allergan affiliate, Clinical Development, Jersey City, USA; 5 Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary Introduction: Schizophrenia is a complex disorder characterized by positive and negative symptoms, and cognitive impairment. Cariprazine, a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is FDA approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adult patients. In a Phase III, 26-week double-blind, randomized, active-controlled trial, cariprazine was significantly more effective than risperidone in
treating negative symptoms and improving function in patients with prospectively identified predominant negative symptoms of schizophrenia. Aims of the study: Data derived from the Positive and Negative Syndrome Scale (PANSS) were evaluated in the primary analysis; post hoc analyses of additional PANSS data from this positive study were conducted to further elucidate the effects of cariprazine in the treatment of predominant negative symptoms of schizophrenia. Methods: Subjects with schizophrenia and PANSS factor score for negative symptoms (PANSS-FSNS) 24 with no pseudospecific factors (eg, extrapyramidal and depressive symptoms) were randomized to cariprazine 4.5 mg/d (dose range: 3−6 mg/d) or risperidone 4 mg/d (dose range: 3−6 mg/d) for 26 weeks of doubleblind treatment. The primary efficacy parameter was change from baseline (CfB) to endpoint in PANSS factor score for negative symptoms (PANSS-FSNS) in the intent-to-treat (ITT) population. The secondary efficacy parameter was CfB to endpoint in Personal and Social Performance Scale (PSP), which measured functional improvement. The CfB to endpoint in PANSS factor score for positive symptoms (PANSS-FSPS) was an additional efficacy parameter. Post hoc analyses evaluated CfB in PANSS single items, the PANSS-derived Marder factors (disorganized thought, uncontrolled hostility/excitement, anxiety/depression) [1], and a modified PANSS-based cognitive subscale (items P2, N5, N7, G10, G11) [2]. Results: A total of 461 patients were randomized (1:1) to double-blind treatment; there were 227 cariprazine- and 229 risperidone-treated patients in the ITT population. The least squares mean difference (LSMD) in CfB at Week 26 was statistically significant in favor of cariprazine versus risperidone in PANSS-FSNS (LSMD = −1.46; P = 0.002) and PSP total scores (LSMD = 4.63; P < 0.001). Statistical improvement in favor of cariprazine versus risperidone was seen on the PSP subdomains of self-care (P = 0.004), socially useful activities (P < 0.001), and personal and social relationships (P < 0.001). PANSS-FSPS were low at baseline indicating low levels of positive symptoms in both groups; LS mean CfB was small and similar for cariprazine and risperidone (−1.07 and −1.08, respectively; LSMD = 0.01 [-0.43, 0.45]; P = 0.963). On the PANSS Marder factors, CfB at Week 26 in disorganized thought was on the level of significance in favor of cariprazine (LSMD = −0.63; P = 0.05); changes in the anxiety/ depression and uncontrolled hostility/excitement factors were not statistically different between groups. Significant improvement at Week 26 in favor of cariprazine was seen on the PANSS-based cognitive subscale (LSMD = −0.53; P = 0.028). Conclusion: Statistically significant improvement in negative symptoms and patient function was seen after 26 weeks of monotherapy with cariprazine compared with risperidone in patients with predominant negative symptoms of schizophrenia. Statistically significant improvement was seen in cognitive improvement for cariprazine versus risperidone. References [1] Marder, S.R., Davis, J.M., Chouinard, G. 1997. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry 58, 538–546. [2] Meltzer, H.Y., Cucchiaro, J., Silva, R. 2011. Lurasidone in the treatment of schizophrenia: A randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry 168, 957–967. Disclosure statement: This study is supported by funding from Gedeon Richter, Plc. I, Istv´an Laszlovszky, am an employee of Gedeon Richter Plc.