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Cariprazine and Cognition in Patients with Schizophrenia and Bipolar Disorder: A Systematic Review
Lorena García-Fernández1, Verónica Romero-Ferreiro, Inmaculada Peñuelas-Calvo
1From Clinical Medicine Department, Universidad Miguel Hernández (Dr. García-Fernández); Psychiatry Department, Hospital Universitario de San Juan, Alicante, Spain (Dr. García-Fernández); CIBERSAM-ISCIII (Biomedical Research Networking Centre for Mental Health), Spain (Drs. García-Fernández, Santos, Rodriguez-Jimenez, and Romero-Ferreiro); European University of Madrid (Dr. Romero-Ferreiro); The Research Institute Hospital 12 de Octubre-Imas12 (Drs. Peñuelas-Calvo, Rodriguez-Jimenez, and Romero-Ferreiro), Madrid, Spain; Complutense University of Madrid-UCM (Drs. Peñuelas-Calvo and Rodriguez-Jimenez); Department of Medicine and Medical Specialities, University of Alcala (Dr. Álvarez-Mon); Department of Psychiatry and Mental Health. Hospital Universitario Infanta Leonor (Dr. Álvarez-Mon); Ramón y Cajal Institute of Sanitary Research-IRYCIS (Dr. Álvarez-Mon), Madrid, Spain; Department of Biomedical and Neuromotor Sciences, University of Bologna (Dr. Scala); Faculty of Health Sciences, Universidad Francisco de Vitoria (Dr. Romero-Ferreiro); CIBERESP/ISCIII (Biomedical Research Networking Centre for Epidemiology and PublicHealth/Carlos III Health Institute), Spain (Dr. Romero-Ferreiro); Center for Social and Health Research, University of Castilla-La Mancha (Dr. Jiménez López); Department of Psychiatry, Virgen de La Luz Hospital (Drs. Jiménez López and Santos); Neurobiological Research Group, Technological Institute, University of Castilla-La Mancha (Dr. Santos), Cuenca, Spain.
Background:
Cariprazine (CAR), an antipsychotic with partial agonism at the D3 receptor and higher affinity than dopamine, has shown significant procognitive effects in preclinical animal studies. This study systematically reviews CAR's effects on cognitive measures in patients with schizophrenia and bipolar disorder.
Methods:
Two independent reviewers systematically searched PubMed, Web of Science, Scopus, and the Cochrane Library up to May 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Additional studies were found by hand searching the references of included studies. Eligible studies were randomized controlled trials (RCTs) in English that assessed CAR's effects on cognition in patients with schizophrenia or bipolar disorder. Quality was assessed using the Jadad scale.
Results:
Out of 139 reports, 5 studies (involving 6,104 patients with schizophrenia or bipolar disorder) were included. In schizophrenia, CAR showed better cognitive outcomes (mainly indirect measures) than placebo (PBO) in both early and late stages. It also outperformed risperidone and aripiprazole in attention-related cognitive tests. In bipolar disorder, CAR improved cognition compared to PBO (also using indirect measures). Most studies found the greatest cognitive benefits with low doses of CAR (1.5-3 mg/d).
Conclusions:
CAR improved cognitive measures compared to PBO and other D2 antagonists or partial agonists in RCTs, especially in patients with greater baseline impairment. Thus, CAR may be a promising option for enhancing cognition in schizophrenic and bipolar patients; though, more trials using specific cognitive assessment tools are needed.
Systematic Review Registration:
PROSPERO CRD42023485028.
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