Effects of the Kampo medicine Yokukansan for perioperative anxiety and postoperative pain in women undergoing breast surgery: A randomized, controlled trial.

The short version

This randomized controlled trial with 77 analyzed women explored whether Yokukansan, a traditional Japanese Kampo herbal formula, can reduce anxiety around breast cancer surgery. Kampo is the Japanese adaptation of traditional herbal medicine, and Yokukansan combines seven herbal extracts that are traditionally prescribed for irritability, restlessness, and insomnia. Perioperative anxiety (anxiety in the period around an operation) matters because the authors link it to faster heart rate, higher blood pressure, longer postoperative pain, and a higher risk of postoperative delirium. Common anxiety medicines such as benzodiazepines can cause sedation, which is why a short-course herbal option was tested. Women aged 20 to 60 undergoing partial or total mastectomy at two Niigata hospitals in Japan were randomly assigned to a Yokukansan group or a control group. The Yokukansan group took two 2.5 g doses of a standardized extract granule, one at bedtime the night before surgery and one 2 hours before anesthesia; the control group received water. Anxiety was measured objectively with salivary alpha-amylase (an enzyme that rises with stress) and subjectively with two questionnaires, the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory. Pain was rated on a 100-mm scale the day after surgery. Salivary alpha-amylase just before surgery was lower in the Yokukansan group than in controls (0.88 versus 1.14 on a log scale, p = 0.03), meaning a smaller physiological stress signal at that moment. HADS-Anxiety scores dropped by 2.77 points with Yokukansan and 1.43 points in controls (both significant, though the difference between groups did not reach significance, p = 0.083), and the authors suggest part of the drop may reflect reassurance once surgery was complete. Trait anxiety on the STAI fell by 4.23 points with Yokukansan and did not change in controls (p = 0.92), with a significant group-by-time interaction (p = 0.009). On both questionnaires higher scores mean more anxiety, so falling scores indicate improvement. Pain scores were nearly identical (1.4 versus 1.36, p = 0.70), and no adverse events were observed. The authors suggest two preoperative doses may reduce perioperative anxiety and that further research is justified. Several limitations apply. Patients knew which group they were in because no matching placebo exists for Kampo medicines, so reassurance may explain some of the effect. Salivary alpha-amylase measures stress generally, and the analyzed groups fell short of the planned size, leaving statistical power at 0.708. Pain was low in both groups, so any pain effect remains untested. Larger double-blind, placebo-controlled trials, including more invasive surgeries, are called for.

Key findings

• This randomized controlled trial (a study where people are randomly assigned to a treatment or a comparison group) tested two doses of Yokukansan, a traditional Japanese herbal formula, in 77 women having breast cancer surgery.
• Salivary alpha-amylase (a stress-related enzyme measured in saliva) just before surgery was lower with Yokukansan than in the water-only control group (0.88 versus 1.14 on a log scale, p = 0.03).
• Trait anxiety (a person's general tendency toward anxiety, measured by the STAI-Trait) fell by 4.23 points with Yokukansan and did not change in the control group (p = 0.92); HADS-Anxiety fell in both groups, and the difference between groups was not statistically significant (p = 0.083).
• Pain the day after surgery did not differ between groups (VAS 1.4 versus 1.36, p = 0.70), and no adverse events were reported.
• The evidence is limited: patients knew their group because no placebo was used, the analyzed sample was small (35 and 42 patients), and post-hoc statistical power was 0.708.

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