Bloodletting therapy for primary headache: A systematic review and meta-analysis of randomized controlled trials

Headache is one of the most common symptoms worldwide. This systematic review aimed to assess the effectiveness and safety of bloodletting therapy (BLT) for primary headache. Four English databases, four Chinese databases and five trials registries were searched from inception to 2nd Sep 2022. Randomized controlled trials which compared BLT to no treatment or drugs for primary headache were included. BLT as adjunctive treatment of drugs or acupuncture was also included. Two authors extracted data and assessed the quality of trials through the Cochrane risk of bias tool 2.0 independently. Pain intensity was the primary outcome (e.g. Visual analogue scale, VAS). Meta-analysis (using RevMan 5.4.1) with random effect model was conducted when there was no serious statistical heterogeneity among trials (I²≤75 %). GRADE was used to assess the certainty of evidence. Seventeen trials involving 1123 participants were included. Types of BLT included pricking BLT, wet cupping and bloodletting puncture with plum-blossom needle. The most frequently used BLT acupoint was Tai Yang. Type of comparisons included BLT vs. drugs (n = 3), BLT plus drugs vs. drugs (n = 4) and BLT plus acupuncture vs. acupuncture (n = 10). All included trials were assessed as "high risk of bias". Results showed that BLT plus rizatriptan benzoate tablets was superior to drug alone in reducing VAS (Mean Difference (MD)=-2.07 cm, 95 % Confidence Interval (CI) -2.65 cm to -1.50 cm, P<0.00001) and increasing the number of patients with more than half pain relief (by 39 %). BLT plus acupuncture was superior to acupuncture alone (MD=-0.80 cm, 95 % CI -1.20 cm to -0.41 cm, P<0.00001) for pain relief. However, no difference was found between BLT and drugs on decreasing VAS. The certainty of the overall evidence is very low mainly due to the poor methodological quality and high heterogeneity among trials. Very low certainty evidence suggests that BLT combined with acupuncture or drugs may be more effective in relieving pain of primary headache and other concomitant symptoms. Current evidence does not support confirmatory conclusions about the safety of BLT.