Acupuncture for Depression: A Comprehensive Review

Neuroplasticity and Brain Circuitry Changes

Chronic depression is associated with impaired neuroplasticity – the brain’s ability to form new connections and adapt. Depressed patients often have reduced levels of brain-derived neurotrophic factor (BDNF), a protein important for neuron growth and synaptic plasticity, which can lead to atrophy in areas like the hippocampus. Acupuncture has demonstrated pro-neuroplastic effects that could counteract these deficits. Research shows acupuncture can promote the growth and restoration of nerve cells and increase synapse-related proteins in the brain, thereby improving synaptic connectivity. In animal models, acupuncture elevates BDNF expression and activates signaling pathways (e.g. BDNF/TrkB-mTOR) that are crucial for synaptic plasticity and neurogenesis. These changes mirror the effects of certain antidepressants which also ultimately increase BDNF and synaptic strength. One study in a rodent depression model found acupuncture enhanced hippocampal BDNF levels and reduced markers of oxidative stress, leading to improved depressive behaviors on par with antidepressant medication. There is also evidence that acupuncture can normalize other neurotrophic factors; for instance, a clinical pilot trial noted that both acupuncture and fluoxetine restored glial cell line–derived neurotrophic factor (GDNF) levels in depressed patients’ serum, with acupuncture showing some advantage in regulating GDNF production. Beyond molecular changes, neuroimaging studies reveal that acupuncture can modulate activity in brain regions involved in mood regulation. For example, stimulation of the Baihui (GV20) point in patients with major depression was found to enhance activation of the prefrontal cortex – a region typically underactive in depression – especially in those with severe symptoms. By engaging and “rewiring” neural circuits, acupuncture may improve emotional processing and cognitive control, contributing to symptom relief.

Autonomic Nervous System Balance

Depression is often accompanied by an overactive stress response and autonomic nervous system imbalance – specifically, increased sympathetic (“fight or flight”) activity and reduced parasympathetic (“rest and digest”) tone. Acupuncture appears to help rebalance the autonomic nervous system (ANS). Stimulating certain acupoints can activate parasympathetic fibers, leading to slowed heart rate, lowered blood pressure, and muscle relaxation. Studies measuring heart rate variability (HRV) – an indicator of ANS function – show that acupuncture can increase HRV, reflecting enhanced parasympathetic modulation and stress reduction. Acupuncture’s calming effect is partly why it can alleviate anxiety and insomnia that often co-occur with depression. Additionally, acupuncture has been found to regulate the hypothalamic-pituitary-adrenal (HPA) axis, which controls stress hormone release. Depression is associated with HPA axis hyperactivity and elevated cortisol levels. Acupuncture may normalize this: clinical observations indicate acupuncture treatments can lower high cortisol levels and reduce HPA hyperactivity in depressed patients. By restoring a healthier balance between sympathetic and parasympathetic nervous activity, acupuncture produces a homeostatic effect that can manifest as improved mood and reduced physiological stress. This mechanism is thought to underlie acupuncture’s ability to not only improve emotional symptoms but also physical symptoms of depression (like poor sleep or appetite) that are tied to ANS dysfunction.

Hormonal and Neuroendocrine Regulation

Related to ANS effects is acupuncture’s influence on hormonal regulation. Beyond cortisol, acupuncture may modulate other hormones relevant to depression. Some research suggests it can affect thyroid function, sex hormones, and melatonin, although the strongest evidence is for stress-related hormones. By acting on the brain’s regulatory centers (hypothalamus and pituitary), acupuncture can trigger systemic effects. For instance, needling certain points has been linked to adjustments in the levels of endorphins, which are natural mood enhancers. It may also stimulate the release of oxytocin, associated with social bonding and stress relief. Regarding the HPA-axis hormones, studies indicate that acupuncture can reduce cortisol and modulate levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). By fine-tuning these neuroendocrine networks, acupuncture may alleviate the physiological burden of chronic stress, thereby improving mood. These multifaceted actions provide a biological rationale for the antidepressant effects observed in clinical practice.

Scientific Evidence from PubMed Studies

A growing body of high-quality research has evaluated acupuncture’s efficacy in treating depression. The evidence includes randomized controlled trials (RCTs), systematic reviews, and meta-analyses. Below, we review several key studies—all sourced exclusively from PubMed.

Efficacy as a Stand-Alone Treatment

Randomized Controlled Trials (RCTs):

• Allen et al. (2006): In a landmark U.S. trial (the ACUDep trial), 151 patients with major depression were randomized to receive either depression-specific acupuncture, general (non-specific) acupuncture, or no acupuncture (waitlist control) over 8 weeks. Patients in both acupuncture groups showed significantly greater reductions in depression scores (measured by the Hamilton Depression Rating Scale, HAM-D) compared to the waitlist. However, there was no statistically significant difference between the depression-specific and non-specific acupuncture groups.
  Plain English: Both types of acupuncture worked better than doing nothing, although pinpointing the exact “active” points remains challenging.

• Sun et al. (2013): In a trial of 75 outpatients with major depressive disorder, patients were randomized to receive either electroacupuncture (EA) or the SSRI fluoxetine for 6 weeks. The study found that EA was as effective as fluoxetine in reducing depressive symptoms, with a faster onset of action and fewer side effects.
  Plain English: Electroacupuncture provided similar mood improvements to a common antidepressant, but with quicker relief and fewer unwanted effects.

• Li et al. (2020): This study evaluated 60 patients with depression partially responding to antidepressants. They were randomized to continue medication alone or to receive adjunct electroacupuncture three times per week for 8 weeks. The combined treatment group experienced significantly greater improvement in depressive symptoms and a higher remission rate.

  Plain English: Adding acupuncture to antidepressant treatment helped patients feel better faster and more completely than medication alone.

Systematic Reviews and Meta-Analyses

Review 1: Smith et al. (2018) – Cochrane Review
This Cochrane review analyzed 64 RCTs involving over 7,000 patients with depression. It concluded that acupuncture may reduce depression severity compared to no treatment; however, when compared to sham acupuncture, the additional benefit was smaller and not always statistically significant. The overall quality of evidence was rated as low to very low.
Plain English: Acupuncture appears to help depression more than doing nothing, though its advantage over a placebo procedure is less clear.

Review 2: Armour et al. (2019)
A meta-analysis including 29 RCTs with 2,268 patients found that acupuncture was more effective than usual care and sham acupuncture, and when combined with antidepressants, it produced an even larger effect size (Hedges’ g = 0.84). The analysis also noted that more frequent acupuncture sessions correlated with greater improvement.
Plain English: Acupuncture can boost mood significantly, especially when used along with standard antidepressant medications, and more sessions generally lead to better results.

Review 3: Xu et al. (2023)
In a meta-analysis of 43 RCTs, Xu and colleagues demonstrated that acupuncture alone was as effective as antidepressant medication for major depression, and that adding acupuncture to medication led to superior outcomes compared to medication alone. Patients receiving acupuncture reported fewer adverse effects.
Plain English: Acupuncture works as well as antidepressants for many people and is even more effective when combined with them, with the added benefit of fewer side effects.

Comparison with Conventional Treatments

Antidepressant Medications

• Efficacy: Research shows that acupuncture is roughly comparable to antidepressants (e.g., SSRIs) for treating moderate depression. For example, in Sun et al. (2013), electroacupuncture produced similar reductions in depression scores as fluoxetine.

• Side Effects: Antidepressants can cause side effects such as nausea, sexual dysfunction, weight gain, and insomnia. Acupuncture, on the other hand, generally has minimal side effects—mainly minor local reactions such as bruising or slight pain.

• Onset of Action: While SSRIs may take 4–6 weeks to become fully effective, acupuncture sometimes yields improvements within 2–3 weeks, potentially offering faster relief for some patients.

Psychotherapy (CBT)

• Efficacy: Cognitive-behavioral therapy (CBT) is well-established for depression and often yields long-term benefits. Studies like the ACUDep trial have shown that acupuncture and counseling can produce similar improvements in depression severity over 3–12 months.

• Engagement: CBT requires active patient participation and sometimes a long-term commitment, whereas acupuncture is a passive treatment. Some patients may prefer the relaxation and holistic experience of acupuncture over talk therapy.

• Combination Approaches: Evidence suggests that integrating acupuncture with CBT or medication can enhance outcomes, suggesting that each modality may address different aspects of depression.