Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients

The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.