Background
Some depressed patients receive acupuncture as an adjunct to their conventional medications.

Objective
This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.

Search strategy
English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021.

Inclusion criteria
RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.

Data extraction and analysis
Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies.

Results
This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] ?0.44, 95% confidence interval [CI] ?0.55 to ?0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD ?0.53, 95% CI ?0.84 to ?0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD ?1.11, 95% CI ?1.56 to ?0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.

Conclusion
Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.

Systematic review registration: INPLASY202150008.

Key words: Depression, Acupuncture plus antidepressants, Therapeutic effectiveness, Adverse drug reactions, Systematic review, Meta-analysis