Manual acupuncture plus SSRIs showed strongest short-term depression benefit in China

A systematic review and network meta-analysis of 77 randomized controlled trials conducted in China found that adding manual acupuncture to a selective serotonin reuptake inhibitor was associated with the largest short-term reduction in clinician-rated depression scores among the eight connected treatments evaluated. The analysis included 7,031 participants with major depressive disorder or another clinically diagnosed depressive condition. Manual acupuncture plus an SSRI produced a mean difference of −3.37 Hamilton Depression Rating Scale points compared with SSRI monotherapy, with a 95% Bayesian credible interval of −3.86 to −2.89, indicating greater improvement with the combination in the primary model.

Electroacupuncture plus an SSRI was also associated with better short-term symptom reduction than SSRIs alone, with a mean difference of −2.98 HAMD points and a 95% credible interval of −3.66 to −2.31. Manual acupuncture combined with serotonin–norepinephrine reuptake inhibitors, or SNRIs, also favored combination treatment over SNRI monotherapy, but the estimate was less precise at −3.16 points, with a wide 95% credible interval of −6.03 to −0.28. These were network estimates combining direct and indirect evidence rather than results from a single head-to-head trial.

The manual-acupuncture-plus-SSRI treatment had the highest posterior probability of occupying the most effective position in the network, Rank 8, at 0.466. Manual acupuncture plus SNRIs followed at 0.406, while electroacupuncture plus SSRIs had a Rank 8 probability of 0.076. SSRI monotherapy had a probability of 0.000 for that position. These figures describe the probability that a treatment would occupy a particular rank after uncertainty was incorporated; they are not summary scores of treatment benefit, and a favorable rank does not by itself demonstrate clinical superiority.

The apparent advantage of manual acupuncture did not survive unchanged under a key sensitivity analysis. Because the trials used both the 17-item and 24-item versions of the HAMD, whose score ranges differ, the researchers repeated the analysis using standardized mean differences. In that model, electroacupuncture plus SSRIs had a standardized mean difference of −0.764, with a 95% credible interval of −1.030 to −0.498, relative to SSRI monotherapy. Manual acupuncture plus SSRIs had a standardized mean difference of −0.659, with a 95% credible interval of −0.842 to −0.476. Both combinations therefore remained associated with improvement over SSRI monotherapy, but their relative order reversed.

The underlying literature was broad but clinically uneven. All included studies were conducted in China and had been published between 2003 and 2025. Participants had primary depression or depression associated with post-stroke, postpartum, perimenopausal, cancer-related, chronic-pain and other clinical settings. Treatment lasted from two to 12 weeks, most commonly four to eight weeks. Acupuncture practices also varied: trials used manual or electroacupuncture and, in some cases, other needling or warming methods, with differing acupoints, treatment frequencies, session durations and antidepressant doses. The researchers therefore considered the transitivity assumption connecting the network comparisons to be uncertain and did not perform subgroup or meta-regression analyses by clinical context.

Quality concerns limit confidence in the treatment estimates. Using the Cochrane Risk of Bias 2 tool, the reviewers found concerns about the randomisation process in 66 studies, commonly because allocation concealment was inadequately reported. Deviations from intended interventions raised concerns in 59 studies, often because the roles and standardisation of acupuncture practitioners were insufficiently described. Outcome measurement raised concerns in 59 trials and was rated at high risk in seven, while three studies were considered at high risk for selective reporting. Although 57 studies were rated as low risk for missing outcome data, the overall body of evidence is vulnerable to biases that could exaggerate or obscure the observed effects.

The statistical model converged satisfactorily, and node-splitting detected no significant local inconsistency for most comparisons that could be tested. However, it identified inconsistency between direct and indirect evidence for electroacupuncture plus SSRIs versus manual acupuncture plus SSRIs, with a reported p value of 0.0063. That particular comparison should therefore be viewed cautiously. The investigators also could not establish transitivity with confidence because potential modifiers—including baseline depression severity, treatment duration, clinical setting and intervention details—were incompletely or unevenly reported. The model’s numerical precision should not be confused with certainty about the clinical importance of the effects.

Safety evidence was too sparse to support a claim that acupuncture-antidepressant combinations were safer, less harmful or equivalent to antidepressant monotherapy. The available networks did not show statistically clear differences in nausea and vomiting, dry mouth or headache for manual acupuncture plus SSRIs or electroacupuncture plus SSRIs relative to SSRIs alone, but credible intervals were extremely wide. Some odds ratios for nausea and vomiting were implausibly small, extending across many orders of magnitude; the authors attributed these estimates mainly to sparse events and zero-event cells rather than interpreting them as evidence of strong protection. Treatment discontinuation was reported too infrequently for a meaningful quantitative synthesis.

The review’s central result is therefore a provisional signal for short-term symptom improvement, not a prescription for a preferred treatment. Manual acupuncture plus SSRIs produced the largest raw-score reduction in the principal network, and both manual and electroacupuncture combinations retained a benefit over SSRI monotherapy in the standardized sensitivity analysis. Yet the shift in their relative ordering, local inconsistency, uncertain transitivity, risk-of-bias concerns, heterogeneous clinical populations and lack of long follow-up prevent a definitive treatment hierarchy. Preclinical studies have proposed effects on serotonergic transmission, stress-axis regulation, neuroimmune signalling and mood-related brain circuits, but such mechanisms remain supportive context and do not prove that acupuncture and antidepressants act synergistically in patients.

Subject of Research: Short-term efficacy and safety of acupuncture–antidepressant combinations for clinically diagnosed depressive disorders in China

Article Title: Acupuncture–antidepressant combinations for clinically diagnosed depressive disorders in China: a systematic review and network meta-analysis

Article References: Qiu, Q., Zhang, Z., Yang, W., Tew, W. Y., Liu, C., Leong Bin Abdullah, M. F. I., Yam, M. F., & Yang, S. (2026). Acupuncture–antidepressant combinations for clinically diagnosed depressive disorders in China: a systematic review and network meta-analysis. Frontiers in Psychiatry, 17, Article 1805745. https://doi.org/10.3389/fpsyt.2026.1805745

Image Credits: AI Generated

DOI: 10.3389/fpsyt.2026.1805745

Keywords: acupuncture, antidepressants, major depressive disorder, network meta-analysis, selective serotonin reuptake inhibitors, electroacupuncture, depression symptoms, systematic review, randomized controlled trials, treatment safety, antidepressant, combinations