Abstract
BackgroundNegative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms. MethodsUsing post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227). ResultsChange from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P < .05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P < .01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P < .05). ConclusionsSince items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.
Highlights
Schizophrenia, an often chronic and debilitating psychiatric disorder, is characterized by a constellation of clinical signs and symptoms that are categorized into distinct positive, negative, disorganization and cognitive symptom domains
Baseline values Mean baseline values for individual Positive and Negative Syndrome Scale (PANSS) Negative and Positive subscale items were similar between groups (Table 2) and supported that inclusion criteria succeeded in selecting a patient population with at least moderate negative symptoms and mild positive symptoms
On the individual items of the PANSS-FSNS, significant differences in change from baseline at week 26 were seen in favor of cariprazine over risperidone on 4 of the 5 negative symptom items included in the factor (N1, N2, N3, N4); no between-group difference was noted for N6 (Fig. 1A)
Summary
Schizophrenia, an often chronic and debilitating psychiatric disorder, is characterized by a constellation of clinical signs and symptoms that are categorized into distinct positive, negative, disorganization and cognitive symptom domains. A significant between-group difference for cariprazine versus risperidone was seen on the secondary efficacy parameter, the Personal and Social Performance Scale (PSP) [25], demonstrating that negative symptom improvement was accompanied by improvement in dayto-day functioning for cariprazine-treated patients. This well-designed large-scale study in patients with schizophrenia and PPNS provided important evidence of the clinically significant superiority of cariprazine over another second-generation antipsychotic in treating negative symptoms. To further evaluate negative symptom improvement with cariprazine in prospectively defined patients with schizophrenia and PPNS, we assessed changes in PANSS individual subscale items and PANSSderived factors using post hoc analyses. Given the results of the original trial, we expect that our more detailed investigations will show that cariprazine has greater efficacy than risperidone on negative symptoms and related constructs when change from baseline to week 26 is assessed using PANSS individual items and PANSS-derived factors
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