Abstract
BACKGROUND: This systematic review aimed to assess the efficacy and safety of acupuncture for generalized anxiety disorder (GAD), with a particular focus on acupuncture alone and acupuncture combined with medication, compared with medication or sham acupuncture. METHODS: We searched MEDLINE/PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov up to August 31, 2025. Randomized controlled trials (RCTs) of acupuncture for GAD were independently screened and extracted by two reviewers following strict quality assessment. Risk of bias was evaluated using the RoB 2.0 tool, evidence certainty was assessed with the GRADE approach, and meta-analyses were conducted with RevMan 5.3. Subgroup analyses were performed according to comparator type and acupuncture parameters (treatment modality, duration, frequency, and sessions). RESULTS: A total of 41 RCTs involving 3,209 participants were included. Meta-analysis showed that acupuncture alone (MD -1.79, 95% CI -2.69 to -0.88; 19 studies) and acupuncture combined with medication (MD -2.26, 95% CI -3.05 to -1.48; 20 studies) were superior to medication alone in reducing Hamilton Anxiety Rating Scale (HAMA) scores. Acupuncture also outperformed sham acupuncture (MD -3.46, 95% CI -4.76 to -2.16; 3 studies). Significant improvements were also observed in total effective rate, Self-Rating Anxiety Scale (SAS) scores, and Clinical Global Impression-Efficacy Index (CGI-EI), with lower rates of adverse events in the acupuncture groups. Subgroup analyses suggested that a treatment duration of 4-6 weeks was associated with better outcomes; for stand-alone acupuncture, a frequency of seven sessions per week was more effective than medication, while for combined therapy, a frequency of 2-4 sessions per week was more effective than medication. DISCUSSIONS: This meta-analysis indicates that acupuncture, either as a monotherapy or in combination with medication, may provide superior efficacy to medication and sham acupuncture, with fewer adverse events. However, most included studies were rated as having "some concerns" in risk of bias by RoB 2.0, and GRADE assessment suggested low or very low certainty of evidence for the primary outcome (HAMA). Egger's test indicated no significant publication bias in HAMA. Further high-quality, large-scale RCTs are required to confirm these findings. REGISTRATION: The protocol of the review was registered in PROSPERO (CRD42015016033).