Background:Kv7 neuronal channels are recognized as a potential drug target for anxiolytic effects. We hypothesize that flupirtine as a potassium channel opener would effectively reduce the preoperative anxiety of patients undergoing craniotomy procedure.Methods:In prospective-double-blinded fashion, 124 counseled patients were randomized to receive 5 sequential doses of capsule flupirtine 100 mg (F Group) or physically similar starch capsules (C Group), at 12 h intervals during preoperative hospitalization. Primary outcome included various aspects of patient anxiety measured by visual analog scale (VAS) just before preoperative counseling and 2 h after the completion of drug regimen under trial. Statistical tool included Mann–Whitney U-test and Wilcoxon signed rank test.Results:Baseline VAS scores were higher for fear of surgical harm, being at the mercy of medical staff, and not awakening after surgery. A significant decline in VAS scores was observed after the completion of drug regime, but to a higher extent in flupirtine-treated patients; it achieved statistical significance in comparison to Group C. No side effects were observed in any patient.Conclusion:Flupirtine is a useful premedication in conjunction with behavioral therapy to alleviate patient anxiety during the preoperative period.