Acupuncture as Add-on Therapy to SSRIs Can Improve Outcomes of Treatment for Anxious Depression: Subgroup Analysis of the AcuSDep Trial

Abstract

Purpose

Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).

Patients and Methods

Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.

Results

Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.

Conclusion

For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.

Clinical Trials Registration

ChiCTR-TRC-08000297.

Keywords:

• anxious depression
• non-anxious depression
• acupuncture
• SSRIs
• subgroup analysis

Abbreviations

AD, anxious depression; NAD, non-anxious depression; MDD, major depressive disorder; STAR*D, Sequenced Treatment Alternatives to Relieve Depression; AcuSDep, Acupuncture as add-on treatment of SSRIs for Depression; PRCT, pragmatic randomized controlled trial; MA, manual acupuncture; EA, electroacupuncture; SSRIs, selective serotonin reuptake inhibitors; HAMD-17, 17-items Hamilton Depression Scale; ASF, anxiety/somatization factor; SDS, Self-Rating Depression Scale; CGI, Clinical Global Impression; SI, severity of illness; SERS, Rating Scale for Side Effects; WHOQOL-BREF, WHO Quality of Life-BREF; mITT, modified intention-to-treat; LOCF, last observation carried forward; GLMM, Generalized linear mixed model.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to their containing information that could compromise the privacy of participants.

Acknowledgments

The authors are very grateful to all the study participants, sincerely thank the team of AcuSDep for their efforts and contributions.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant number 82004445); the National Science and Technology Support Program of China (grant number 2006BAI12B05-2); the Young Talents Lifting Project of Beijing Association for Science and Technology (grant number BYESS2023338). The funding sources had no role in the study design, data collection, analysis, interpretation of data or manuscript preparation.