Direct and indirect effects of paliperidone extended-release tablets on negative symptoms of schizophrenia

Abstract

Direct and indirect effects of the new psychotropic paliperidone extended-release (paliperidone ER) tablets on negative symptom improvement in schizophrenia were investigated using path analysis. A post hoc analysis of pooled data from three 6-week, double-blind, placebo-controlled studies of paliperidone ER in patients experiencing acute exacerbation was conducted. Regression analysis explored relationships between baseline/study characteristics and negative symptoms. Change in Positive and Negative Syndrome Scale (PANSS) negative factor score at endpoint was the dependent variable; explanatory variables included demographic and clinical characteristics. Path analysis determined direct and indirect effects of treatment on negative symptom change. Indirect mediators of negative symptom change in the model included changes in positive symptoms, anxiety/depression symptoms and movement disorders. Path analysis indicated that up to 33% of negative symptom improvement was a direct treatment effect. Indirect effects on negative symptoms were mediated through changes in positive symptoms (51%) and anxiety/depression symptoms (18%), whereas changes in movement disorders had a 2.1% inverse effect. Path analysis indicated that paliperidone ER has a direct effect on negative symptoms. Negative symptom improvement also was indirectly mediated via changes in positive and depressive symptoms.

Keywords: antipsychotic; paliperidone ER; path analysis; psychotropic; schizophrenia.

Figure 1

Path model illustrating the relationships between the direct and indirect effects of treatment from positive symptoms, anxiety/depression symptoms, and EPS symptoms on negative symptoms. P1 Through P7 are path coefficients. Abbreviation: EPS, extrapyramidal symptoms.

Figure 2

Estimated path coefficients for the comparisons of effects of all paliperidone ER doses combined vs placebo. The numbers in parentheses are the coefficients of the intermediate paths; the coefficient of the indirect path can be obtained by multiplying the coefficients of the intermediate paths. Sample interpretation, for positive symptoms: the first intermediate path shows that paliperidone ER treatment (all doses combined) was associated with a P1: −3.95-unit greater change in positive symptoms than placebo, after controlling for the baseline score; the second intermediate path shows that there was a P5: 0.35-unit effect of positive symptoms on negative symptoms, after controlling for the other symptoms. The product of the intermediate path coefficients ([−3.95]*[0.35] = −1.39) shows that paliperidone ER treatment (all doses combined) was associated with a 1.39-unit greater improvement in negative symptoms via positive symptom improvement vs placebo. Abbreviations: EPS, extrapyramidal symptoms; ER, extended-release.

Figure 3

Percentage of the total treatment effect due to direct or indirect effects contributing to change in the negative factor score at endpoint, all paliperidone ER doses combined. Abbreviations: ER, extended-release; SAS, Simpson-Angus Scale.