Efficacy and safety of 3-n-butylphthalide for the treatment of cognitive impairment: A systematic review and meta-analysis

CNS Neurosci Ther. 2022 Nov;28(11):1706-1717. doi: 10.1111/cns.13952. Epub 2022 Sep 1.


Background: Current evidence for the efficacy of pharmacological treatment in improving cognitive function is absent. Recent studies have reported that 3-n-butylphthalide (NBP) has a positive effect on improving cognitive impairment; however, its clinical efficacy and safety is unclear. Therefore, we conducted a meta-analysis to assess its efficacy and safety for cognitive impairment.

Methods: We systematically searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases, and two reviewers independently screened and extracted the data from included studies. We synthesized the data using the Review Manager Software version 5.3.

Results: We included six randomized clinical trials (RCTs), encompassing 851 patients with cognitive impairment. The results showed that NBP improved cognitive impairment. Specifically, the clinical efficacy was better than that in the control group, with better performance in improving the Mini-Mental State Examination and the Montreal Cognitive Assessment scores, while decreasing the Alzheimer's Disease Assessment Scale-Cognitive subscale and the Clinician's Interview-Based Impression of Change plus caregiver input scores. There was no significant difference in the incidence of adverse events between both groups.

Conclusion: The NBP is effective and safe in improving cognitive impairment; however, more high-quality RCTs are needed to confirm these findings.

Keywords: 3-n-butylphthalide; MMSE; MoCA; cognitive impairment; meta-analysis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans* / adverse effects
  • Cognition
  • Cognition Disorders* / drug therapy
  • Cognition Disorders* / etiology
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / drug therapy
  • Humans


  • Benzofurans
  • 3-n-butylphthalide