Neuroimaging studies of acupuncture for depressive disorder: a systematic review of published papers from 2014 to 2024

Acupuncture in the treatment of depression has been the subject of growing scientific interest in recent decades. Depression affects approximately 300 million people worldwide and is projected to become the leading cause of economic and medical burden related to disease by 2030. Although conventional antidepressants are effective for many patients, they have significant limitations, including prolonged side effects, drug resistance, and symptom recurrence. Some patients do not respond adequately to medications or experience worsening of emotional and physical symptoms, increasing the risk of comorbidities.

In this context, acupuncture has emerged as a promising therapeutic alternative, offering a non-pharmacologic approach that can significantly improve both the physical and psychological symptoms of depression. This ancient Chinese technique works through the stimulation of specific points, promoting regulation at multiple levels and therapeutic targets. With advances in medical imaging techniques, particularly neuroimaging technologies, it has become possible to scientifically explore the mechanisms by which acupuncture exerts its therapeutic effects on the brain.

This systematic study had as its primary objective to analyze and evaluate the neuroimaging evidence on the impact of acupuncture in patients with depressive disorder, identifying specific central targets and brain networks influenced by the therapy. The investigators conducted a comprehensive search in eight databases, including PubMed, Cochrane Library, EMBASE, Web of Science, and Chinese databases, covering studies published between February 2014 and February 2024. Only controlled studies that used at least one neuroimaging technique to evaluate the effects of acupuncture in patients diagnosed with depressive disorder were included. The methodology encompassed several types of acupuncture intervention, such as manual acupuncture, electroacupuncture, transcutaneous auricular vagus nerve stimulation, and transcutaneous vagus nerve stimulation.

The methodological quality of the studies was assessed using standardized tools for randomized and non-randomized studies. Data were extracted following rigorous guidelines and analyzed qualitatively due to significant methodological differences among the studies.

The results revealed consistent and clinically relevant findings. Twenty-six studies were included, involving a total of 1,138 participants — 742 patients with depression and 396 healthy controls. All studies used magnetic resonance imaging as a neuroimaging technique, demonstrating that acupuncture can affect neural activity in specific brain regions associated with depression. The most frequently affected areas include the cingulate gyrus, precuneus, insula, prefrontal lobe, middle frontal gyrus, cerebellum, hippocampus, putamen, angular gyrus, superior frontal gyrus, thalamus, and amygdala.

These regions are primarily located in neural networks critical for emotional regulation, including the default mode network, limbic system, emotional and cognitive regulation network, reward network, central executive network, and sensorimotor network. Particularly interesting was the observation that the neuroimaging results in most patients with depression correlated significantly with scores on the Hamilton Depression Rating Scale, providing clinical validation for the observed neurological changes.

The clinical implications of these findings are substantial for both patients and clinicians. For patients, the results offer robust scientific evidence that acupuncture produces measurable and beneficial changes in brain activity, particularly in regions associated with emotional regulation and cognitive processing. This suggests that acupuncture is not merely a placebo effect but an intervention that induces real neuroplastic changes in the brain. The increase in functional connectivity in regions related to emotional regulation may help explain how acupuncture relieves depressive symptoms and improves patients' overall well-being.

For clinicians, these findings can aid in the identification of biomarkers that predict treatment response, allowing more personalized therapeutic plans and increasing the effectiveness of acupuncture in the treatment of depression. By understanding the neurological mechanisms underlying the effects of acupuncture, clinicians can be better prepared to use acupuncture as an adjunct treatment, especially for patients resistant to conventional therapies. The correlation between neuroimaging changes and clinical improvement also provides an objective tool for monitoring treatment progress.

Despite the promising findings, the study has several important limitations that must be considered. All 26 included studies were conducted in mainland China, limiting the applicability of the findings to other populations and cultural contexts. In addition, all were non-randomized controlled studies, with 15 of them showing a 'serious' risk of bias due to participant dropout. The absence of adequate randomization and allocation concealment, together with the lack of blinding in most studies, compromises overall methodological quality.

The studies also varied significantly in their intervention techniques, including needle retention time, intensity, and frequency, which may have influenced the results. Most studies included more female than male patients, and many had relatively small sample sizes, which may reduce the statistical power of the findings. Finally, all studies used only magnetic resonance imaging as a neuroimaging technique, limiting multimodal understanding of the effects of acupuncture on the brain.

This study represents the most current and comprehensive systematic review of neuroimaging and acupuncture for depression, providing evidence that acupuncture induces functional changes in distinct brain regions associated with emotional regulation and cognitive processing. The findings suggest that acupuncture may have regulatory effects on the abnormal functioning of neural regions and networks in individuals diagnosed with depression. However, high-quality randomized controlled trials with multimodal designs and better integration of neuroimaging data are needed to fully elucidate the mechanisms by which acupuncture impacts patients with depressive disorder and to establish more precise clinical guidelines for its therapeutic use.