Implicaciones sobre la funcionalidad, el rendimiento cognitivo, la hiperprolactinemia y el funcionamiento sexual del cambio de risperidona a paliperidona palmitato en esquizofrenia

Abstract

Implications for functionality, cognitive performance, hyperprolactinemia, and sexual functioning of switching from risperidone to paliperidone palmitate in schizophrenia Introduction: Schizophrenia is one of the leading causes of disability worldwide. Cognitive impairments are a core symptom of the illness and are associated with poorer functional outcomes. Risperidone and paliperidone are two widely used atypical antipsychotics for the treatment of schizophrenia, both available in long-acting injectable formulations (long-acting injectable risperidone [R-LAI] and paliperidone palmitate [PP]), which have demonstrated improved outcomes in relapse prevention and reduced risk of rehospitalization. Although paliperidone, or 9-hydroxy-risperidone, is the active metabolite of risperidone, previous studies suggest that paliperidone may offer a better profile in terms of social functioning and cognitive abilities, as well as a more favourable tolerability profile. Objectives: To examine whether, in patients with schizophrenia, switching from risperidone (oral or R-LAI) to PP under pragmatic conditions leads to improvements in social functioning and cognitive performance. Additionally, the study evaluates the effects of switching from risperidone to PP on sexual function and prolactin levels. Methods: A total of 38 patients diagnosed with schizophrenia (DSM-IV criteria) who had been receiving stable doses of risperidone monotherapy (oral or R-LAI) for at least two months and whose psychiatrists indicated a switch to PP were included. Three assessments were conducted: 1) baseline (before the switch), 2) three months post-switch, and 3) six months post-switch. At each visit, social functioning was assessed using the Personal and Social Performance (PSP) scale, cognitive performance was evaluated with the MATRICS Consensus Cognitive Battery, and sexual functioning was measured using the Arizona Sexual Experience Scale (ASEX). Plasma levels of prolactin and sex hormones were also determined at each assessment. Statistical analyses were conducted on a final sample of 27 patients who completed at least one follow-up visit. Statistical analyses were performed using R. Linear mixed models were used to explore longitudinal changes in social functioning, cognitive outcomes, prolactin levels, and sexual function, with significance set at p < 0.05. Results: The findings indicate a significant improvement in functionality following the switch from risperidone to PP. A sensitivity analysis revealed a significant negative interaction between time and the maintenance dose of PP (greater improvement observed in patients receiving lower doses compared to higher doses). Regarding longitudinal changes in cognitive functioning, patients showed improvement in 6 out of 10 cognitive tasks, those involving processing speed, working memory, visual memory, reasoning and problem-solving, and attention and vigilance. Among women, prolactin levels decreased after the switch, with a significant time effect. Antipsychotic dosage influenced prolactin levels, as higher doses were associated with higher prolactin concentrations. No significant differences were found in total ASEX scores six months after the switch. Conclusions: The results suggest that switching from risperidone to PP may positively impact cognitive performance and social functioning in patients with schizophrenia, particularly among those receiving lower doses of PP. Furthermore, switching from risperidone to PP may reduce prolactin levels in women with schizophrenia, indicating that this switch may be considered a beneficial therapeutic option in women with schizophrenia and hyperprolactinemia.

Date of Award	17 Oct 2025
Original language	Spanish
Awarding Institution	Universitat Autònoma de Barcelona (UAB)
Supervisor	Juan David Barbero Valverde (Director) & Javier Labad Arias (Director)