Detoxification improves multidomain cognitive dysfunction in high-dose benzodiazepine abusers

Purpose: High-dose benzodiazepines (BZDs) abuse has been documented to cause multidomain cognitive dysfunction. We explored whether cognitive abnormalities to high-dose BZD abuse might be reversed by detoxification with slow subcutaneous infusion of flumazenil. Methods: We recruited 96 patients consecutively admitted to the Department of Internal Medicine, Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. After selection for inclusion and exclusion criteria, 50 patients (23 men, 27 women; age 42.7 ± 10.3 years) were included. They underwent a comprehensive neuropsychological battery to explore verbal memory, visuospatial memory, working memory, attention, and executive functions 28-30 days prior to admission for detoxification (T0) and at the end of detoxification, i.e., 7 days after admission (T1). A group of 50 healthy adults (24 men, 26 women; mean age 44.5 ± 12.8 years) matched for age, sex, and education served as controls. Results: At T0, patients scored significantly worse than healthy controls in all the neuropsychological tests. Depression and anxiety scores were associated with impaired verbal memory at T0 in patients. T1-T0 comparison showed improved performances in all neuropsychological tests after the end of detoxification in patients. Conclusion: We confirmed that all neuropsychological domains were significantly and profoundly impaired by high-dose BZD abuse and documented that cognitive abnormalities improved after detoxification with slow subcutaneous infusion of flumazenil.