Purpose: Theory of mind (ToM) is an important part of social cognitive function and is associated with medial prefrontal cortical (mPFC) activity. This study aimed to evaluate the efficacy of paliperidone in improving ToM task performance in patients with schizophrenia compared with haloperidol.
Patients and Methods: This study was a single-center, single-blinded (assessor), parallel-group randomized clinical trial of patients with schizophrenia randomized to paliperidone or haloperidol. ToM was assessed at weeks 0, 8, 12, and 16 using the first-order belief, higher-order belief, faux-pas, and Reading the Mind in the Eyes tests. The primary outcome was the change in the ToM performance scores from baseline to after 16 weeks of treatment.
Results: The participants received paliperidone (n = 29) or haloperidol (n = 31). For the first-order belief task, there were no between-group differences (P > 0.05) but time differences in both groups (P < 0.05). For the higher-order belief task, there were no between-group differences (P > 0.05), but there were time differences in both groups (P < 0.05) and a time×group interaction in the paliperidone group only (P < 0.05). For the faux-pas task, there was a difference between groups at week 16 (P < 0.05), and the improvement in time was significant for the paliperidone group only (P < 0.05). For the Reading the Mind in the Eyes task, there was an improvement over time for the paliperidone group only (P < 0.05). Safety was manageable in both groups.
Conclusion: Paliperidone treatment might be more effective than haloperidol in improving ToM task performance in schizophrenia.
Trial Registration: chictr.org.cn_identifier ChiCTR-IPR-15007635.
Keywords: schizophrenia, theory of mind, longitudinal study, paliperidone, haloperidol