Effectiveness and Safety of Acupuncture for Perimenopausal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This comprehensive meta-analysis examined 16 randomized controlled trials involving 1,311 perimenopausal women with depression, comparing the efficacy of acupuncture with that of conventional antidepressants. The study represents one of the most rigorous analyses ever conducted on this topic, applying strict inclusion criteria and robust analytical methods. Perimenopausal depression affects between 4.7% and 41.8% of women in this phase of life, which is characterized by significant hormonal fluctuations that contribute to unique depressive symptoms, differing from general depression. Conventional treatments, including antidepressants and hormone replacement therapy, often show limited efficacy and significant side effects, motivating the search for safer and more effective therapeutic alternatives.

All 16 included studies were conducted in China, encompassing both manual acupuncture and electroacupuncture. The experimental group of 660 patients received acupuncture treatment, while the control group of 651 patients was treated with various antidepressants, including fluoxetine, escitalopram, and flupentixol/melitracen. Treatment duration ranged from 2 to 12 weeks. The results demonstrated consistent superiority of acupuncture across multiple measures.

The efficacy rate was significantly higher in the acupuncture group (OR = 2.68, 95% CI: 1.84-3.90, p < 0.00001), indicating that patients treated with acupuncture had 2.68 times higher odds of showing significant clinical improvement. Analysis of Hamilton Depression Rating Scale (HAMD) scores revealed greater reductions in the acupuncture group (-1.89 points, 95% CI: -2.35 to -1.44, p < 0.00001). Both manual acupuncture and electroacupuncture demonstrated greater efficacy than antidepressants, with manual acupuncture showing slightly more robust effects. A particularly important aspect was the follow-up analysis, showing that the benefits of acupuncture are more lasting than those of antidepressants (-2.4 points on the HAMD during follow-up, p < 0.00001).

Regarding safety, acupuncture had a significantly more favorable profile, with an incidence of adverse events 77% lower than antidepressants (OR = 0.23, 95% CI: 0.1-0.52, p = 0.0004). Adverse events related to acupuncture were mainly mild and transient, including subcutaneous hematomas and mild pain at the application site, contrasting with the more severe side effects of antidepressants, such as dry mouth, fatigue, weight gain, and sexual dysfunction. Interestingly, analysis of hormone levels (FSH, E2, and LH) showed no significant differences between groups, suggesting that the antidepressant mechanisms of acupuncture may be independent of direct hormonal fluctuations. This points to possible neurobiological mechanisms, such as modulation of the limbic-paralimbic-neocortical networks of the brain and increased brain-derived neurotrophic factor.

The study has important limitations, including the exclusion of placebo or sham acupuncture studies, all trials having been conducted in China, and variable methodological quality of the included studies. Heterogeneity among studies was generally low to moderate, strengthening the reliability of the results. The clinical implications are substantial, suggesting that acupuncture may be considered a first-line treatment for perimenopausal depression, offering superior efficacy, a better safety profile, and longer-lasting benefits compared with conventional antidepressants.