Treatment of Depression with Acupuncture Based on Pathophysiological Mechanism

This review, published in the International Journal of General Medicine in 2024, presents a comprehensive analysis of the pathophysiologic mechanisms through which acupuncture acts in the treatment of depression. The authors, Sun and colleagues, conducted a narrative literature review to explore how this ancient therapy can offer a safe and effective alternative to conventional depression treatments. Depression is recognized as a prevalent mental disorder that profoundly affects an individual's psychologic and physical well-being, characterized by persistently depressed mood, loss of interest, decreased energy, and cognitive dysfunction. The study highlights that, although traditional treatments rely mainly on medications and psychotherapy, these methods are not always effective for every patient and frequently produce significant side effects.

The investigators identified four principal mechanisms by which acupuncture exerts its antidepressant effects. The first mechanism involves the modulation of neurotransmitter levels. Acupuncture has been shown to increase serotonin, dopamine, and norepinephrine levels in the brain — neurotransmitters fundamental to mood regulation. Animal-model studies have shown that acupuncture can significantly increase activity at 5-HT1A and 5-HT1B receptors, thereby improving depressive behavior.

Electroacupuncture, a variation of the traditional technique, has proved particularly effective in modulating the dopaminergic system in the prefrontal cortex. The second mechanism identified is modulation of the neuroendocrine axis, particularly the hypothalamic-pituitary-adrenal (HPA) axis. In patients with depression, this axis frequently shows hyperactivity, resulting in elevated cortisol levels. Acupuncture has been shown to lower blood cortisol levels and reduce HPA-axis hyperactivity, restoring the balance between the sympathetic and parasympathetic nervous systems.

This homeostatic effect not only reduces depressive symptoms but also promotes overall neuroendocrine balance. The third mechanism involves the enhancement of neuroplasticity. Neuroplasticity, which refers to the nervous system's capacity to adapt to environmental change, tends to be impaired in patients with depression. Acupuncture has been shown to promote the growth and reconstruction of nerve cells in the brain through activation of the BDNF/mTORC1 signaling pathway.

This pathway is crucial for the formation and functional maintenance of synaptic connections. Studies have shown that acupuncture can increase the expression of synapse-related proteins such as PSD95, synapsin I, and GluR1 and increase dendritic spine density in the prefrontal cortex. The fourth mechanism identified is acupuncture's anti-inflammatory effect. Depression is frequently associated with an increased inflammatory response, with patients showing elevated levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.

Acupuncture has been shown to reduce the production and release of these inflammatory mediators while promoting the release of anti-inflammatory factors such as IL-10. Animal studies have shown that acupuncture can inhibit activation of the NLRP3 inflammasome, a protein complex involved in the inflammatory response and pyroptotic cell death. The clinical results presented in the review consistently show that acupuncture can significantly improve depressive symptoms through these multiple mechanisms. In animal models of depression, acupuncture has been shown to reduce depressive behaviors, improve neurologic function, and normalize biomarkers associated with depression.

Electroacupuncture, in particular, has proved effective in reversing behavioral changes induced by chronic stress and restoring normal synaptic function. The clinical implications of these findings are substantial. Acupuncture offers a therapeutic approach that acts through multiple biologic pathways simultaneously, providing a comprehensive antidepressant effect. Unlike conventional antidepressant medications, which frequently cause side effects such as nausea, vomiting, diarrhea, and sexual dysfunction, acupuncture has a superior safety profile.

In addition, acupuncture's capacity to modulate neurotransmitters, inflammation, neuroplasticity, and the neuroendocrine system simultaneously suggests that it may be particularly effective for patients who do not respond adequately to conventional treatments. However, the authors acknowledge important limitations of their review. The quality and quantity of research on acupuncture are still insufficient to establish it as a broadly accepted medical treatment. In addition, the efficacy of acupuncture varies among individuals, and the technique, if not performed appropriately, can cause side effects such as infection, bleeding, and needle injuries.

Acupuncture treatment also requires multiple sessions and can be time-consuming, which may represent an inconvenience for some patients. The investigators emphasize the need for more controlled and randomized clinical trials to confirm these mechanisms in human populations and establish standardized treatment protocols. They also highlight the importance of considering cultural factors and individual beliefs, given that acupuncture is deeply influenced by the philosophy of traditional Chinese medicine, which may not be compatible with the cultural context of every patient.