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Background Previous studies assessing the neurotoxicity of haloperidol, risperidone and paliperidone in cell culture suggest that paliperidone shows the strongest neuroprotective effect and a reduced apoptosis level. Other studies including patients with schizophrenia suggest that switching from risperidone long-acting injection (RLAI) to paliperidone palmitate (PP) may improve cognitive function in processing speed and attention. We aimed to study whether switching from risperidone to PP is associated with improved cognitive abilities at 3 or 6 months after the switch. Methods Our initial sample included 32 patients with schizophrenia attending to the Department of Mental Health from Parc Taulí Hospital (Sabadell, Barcelona). All patients were treated with oral risperidone or RLAI (at least two months of stable treatment in monotherapy) and had the indication to be switched to PP by their psychiatrists. Of all 32 patients, 24 (75%) had at least a follow-up visit at 3 months. Therefore, statistical analyses were conducted in a final sample of 24 patients (88% men; 35.6 ± 12.3 years; 63% were receiving RLAI at baseline visit). Ethical approval was obtained from the local Ethics Committee and all participants provided written informed consent. Clinical diagnoses for schizophrenia were generated with the OPCRIT checklist v.4.0. Three assessments were completed: 1) baseline (pre-switch), 2) 3 months post-switch, 3) 6 months post-switch. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery, which includes 10 cognitive tests for assessing 7 cognitive domains. Statistical analyses were performed with SPSS v 23.0 (IBM, USA). A non-parametric paired test (Wilcoxon test) was used for comparing changes in cognitive function over time (baseline vs 3 months; baseline vs 6 months). Significance was set at p<0.05. Results Significant improvements in cognitive function were found for two cognitive tasks dealing with processing speed (BACS-SC and TMT-A) and one task dealing with attention and vigilance (CPT-IP) at both 3 and 6 months. Although reasoning and problem solving (NAB Mazes) or spatial working memory (WMS-III-Spatial Span) did not improve at 3 months, significant improvements in these two cognitive tasks were found at 6 months. Verbal memory, visual memory and social cognition did not improve over time. Discussion In patients with schizophrenia, switching from risperidone to PP is associated with cognitive improvement in tasks dealing with processing speed, attention, working memory and reasoning and problem solving. Our findings are in accordance with previous studies that suggest a potential neuroprotective effect of paliperidone. Some limitations of our study include the lack of randomization (no control group) and the small sample size. The small number of female patients does not allow to explore potential sex differences in the improved cognitive outcome.

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