Schizophrenia is a serious neuropsychiatric disease characterized by positive symptoms, negative symptoms and cognitive impairment. Evidence have shown that cognitive impairment sustains in every clinical stage, may relate with the liability, may predict functional outcome in schizophrenia and could be the core symptom of schizophrenia. The treatment of cognitive impairment in schizophrenia could alleviate the burden of the illness and has become the subject of intensive research. In this review, we synthesize current advances of assessing strategies, pharmacological and non-pharmacological treatments of cognitive impairment in schizophrenia. According to the registered records of ClinicalTrials.gov, the most widely studied strategies have aimed at modifying neurochemical mechanisms of dopamine metabolism, glutamate metabolism, γ-aminobutyric acid (GABA) metabolism, serotonin metabolism, acetylcholine metabolism, and oxytocin. Despite preclinical data for putative pro-cognitive drugs, their clinical benefits for schizophrenia patients have been limited. The small sample sizes and the short treatment duration could be related with the suboptimal results. Evidence supported the short-term benefits of cognitive remediation therapy on cognitive domains with small to moderate effects; however, the small sample sizes and the characteristics of subjects limited the generalization of the positive results and the long-term functional outcome is not clear. Combination therapy is promising, by integrating pro-cognitive agents and cognitive rehabilitation programs or combining two kinds of pro-cognitive agents via different mechanisms. Future studies should investigate the pro-cognitive drugs’ long-term efficacy, rebound deterioration in psychosis/cognition following discontinuation, and related biomarkers of functional outcome.
Keywords: Cognitive impairment, schizophrenia, clinical trials.