Cognitive Effects of Lurasidone and Cariprazine: A Mini Systematic Review

Abstract

Background: Cognitive deficits are associated with schizophrenia and show a progressive worsening, often being unresponsive to treatment. New antipsychotic molecules acting as antagonist at the serotoninergic 5-hydroxytryptamine receptor 7 (e.g. lurasidone) or partial agonists at dopamine D3 receptor (e.g. cariprazine) could have an impact on cognition in this patient group. Objective: The aim of the systematic review is to explore the efficacy of lurasidone and cariprazine in improving cognition in both animal models and human studies. Methods: The following terms: (lurasidone AND cognit*) OR (cariprazine AND cognit*) were searched in Web of Science from inception to December 2021. We included all studies that assessed changes in cognitive function after treatment with cariprazine or lurasidone. Results: Of 201 selected articles, 36 were included. Twenty-four articles used animal models (rats, mice and marmosets), five evaluating the effects of cariprazine and 19 the effects of lurasidone. Twelve articles were clinical studies (cariprazine n = 2; lurasidone n = 10). In both animal and human studies lurasidone showed a greater efficacy on cognitive performance compared to placebo, quetiap- ine, ziprasidone or treatment-as-usual. Cariprazine was superior to other antipsychotics in improving cognitive functions in both animal and human studies. Conclusion: The cognitive effect of lurasidone could be explained by its potent antagonism at the 5- HT7 receptors combined with partial agonism at 5-HT1A receptors. The pro-cognitive effect of cariprazine is probably explained by its very high affinity for D3 receptors. Head-to-head studies com- paring lurasidone and cariprazine are needed to establish the “first-choice” treatment for cognitive dys- function associated with schizophrenia.

The trace amine-associated receptor 1 agonists – non-dopaminergic antipsychotics or covert modulators of D2 receptors?

“…Further investigation of this action at the 5-HT7 receptor would be valuable in understanding the clinical effects of ulotaront; 5-HT7 ligands have been proposed to be valuable as potential treatments for a wide range of neuropsychiatric indications ( Nikiforuk, 2015 ). These include cognitive dysfunction ( Gasbarri and Pompili, 2014 ) – 5-HT7 antagonism has been proposed to underlie a relatively greater procognitive effect of lurasidone ( Olivola et al, 2023 ) – and affective disorders ( Gottlieb et al, 2023 ), albeit without any selective ligands currently licensed.…”

Cariprazine and cognition in patients with schizophrenia and bipolar disorder: A systematic review

“…Recently, several studies have been published on the pro cognitive effects of cariprazine in patients with schizophrenia and bipolar disorder, although a systematic review has not yet been carried out with the exception of a minireview that only included 2 clinical studies publish before 2021 (19). Therefore, we ought to systematically review all available studies regarding the effectiveness of cariprazine in the cognitive impairments suffered by people with psychotic symptoms, especially patients with schizophrenia and bipolar disorder.…”