Basic and clinical research on acupuncture for post-stroke depression: A narrative review

Abstract

Post-stroke depression (PSD) is a common neuropsychiatric complication affecting 20%-65% of stroke survivors, with limited therapeutic options due to the side effects of antidepressants. This narrative review synthesizes recent advances in acupuncture for PSD, highlighting its multi-target mechanisms and clinical applications. Acupuncture regulates neurotransmitters (e.g., 5-hydroxytryptamine, norepinephrine, glutamate), neurotrophic factors (e.g., brain-derived neurotrophic factor), the hypothalamic-pituitary-adrenal axis, inflammatory cytokines (e.g., interleukin-6, tumor necrosis factor-alpha), and oxidative stress, while modulating the brain-gut axis and homocysteine levels. Clinically, pure acupuncture, electroacupuncture, scalp/auricular acupuncture, and comprehensive therapies (combined with herbs, moxibustion, music, or rehabilitation) demonstrate efficacy in improving depressive symptoms and daily function. However, research gaps include standardized treatment protocols, mechanistic exploration, and large-scale controlled trials. This review underscores acupuncture’s potential as a safe, multi-modal therapy for PSD and highlights areas for future research.

Key Words: Post-stroke depression; Acupuncture; Mechanisms; Clinical applications

Core Tip: This narrative review systematically summarizes the current status of basic research and clinical research of acupuncture in the management of post-stroke depression (PSD). It also discusses existing challenges, such as inconsistent research standards and insufficient high-quality evidence, and provides perspectives for future studies, aiming to offer a comprehensive reference for clinical practice and related research on acupuncture for PSD.

INTRODUCTION

Post-stroke depression (PSD) represents a prevalent neuropsychiatric complication following stroke, characterized by mood lability, cognitive slowness, insomnia, and even suicidal ideation[1]. With approximately one-third of stroke survivors developing PSD, it imposes a substantial burden on recovery outcomes, healthcare systems, and caregivers[2]. Beyond its high prevalence (reported between 20% and 65% across studies), PSD is particularly concerning as it significantly impedes rehabilitation progress, reduces quality of life, and increases mortality risk, especially among older adult populations[3]. Current clinical management primarily relies on serotonin reuptake inhibitors, which ameliorate depressive symptoms but are associated with substantial side effects, including central nervous system disturbances, gastrointestinal issues, and heightened cardiovascular risks with long-term use[4]. Furthermore, the delayed onset of action and variable efficacy of antidepressants underscore the unmet medical need for effective, well-tolerable, and timely interventions for PSD management.

Acupuncture, a key component of traditional Chinese medicine (TCM), stimulates specific somatic points to modulate physiological functions and has gained global recognition for managing neurological and psychiatric conditions, supported by a favorable safety profile[3]. By contrast, acupuncture—an integral component of TCM—has emerged as a promising therapy for PSD, offering significant efficacy with minimal adverse effects[5]. Clinical evidence demonstrates that acupuncture not only alleviates emotional and cognitive deficits in patients with PSD but also circumvents the systemic toxicity of pharmacotherapy, underscoring its high clinical value[6,7]. However, the underlying mechanisms of acupuncture in PSD remain incompletely understood, necessitating further investigation.

This narrative review synthesizes recent advances in the basic and clinical research of acupuncture for PSD, aiming to provide insights for mechanistic exploration and therapeutic optimization.

MECHANISTIC ADVANCES IN ACUPUNCTURE FOR PREVENTING AND TREATING PSD

Regulation of neurotransmitters

Human mental activities and emotional changes are predominantly modulated by various neurotransmitters, which exert extensive biological activities through brain tissues such as the thalamus, basal ganglia, and cerebral cortex[8]. Studies have found that the occurrence of PSD is closely related to abnormalities in brain neurotransmitters. It is generally believed that changes in the content of monoamine neurotransmitters and amino acid neurotransmitters in brain tissue are the main factors leading to PSD pathogenesis[9,10].

Regulation of monoamine neurotransmitters: Monoamine neurotransmitters in brain tissue mainly include 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE), which are mainly involved in processes such as human sleep and emotional regulation. Among them, 5-HT, which plays an important role, exerts its effects mainly by binding to specific 5-HT receptors (e.g., 5-HT1A, which is associated with mood regulation and neurogenesis, and 5-HT2A), activating intracellular second messengers to generate cascade reactions, and terminates with the reuptake of 5-HT by nerve cells, thereby regulating emotions[11]. After stroke, lesions in the brain will damage structures such as the brainstem locus coeruleus, and the neurons projecting 5-HT and NE to the left thalamus and frontal lobe and their conduction pathways are also destroyed, thereby inhibiting the synthesis of neurotransmitters such as 5-HT, NE, and DA, and ultimately producing depressive emotions[11]. Clinical studies have found that the severity of PSD is negatively correlated with serum 5-HT levels: When patients with PSD show depressive manifestations such as low mood and bradykinesia, the activity and concentration of serum 5-HT are lower than the normal level; when the serum 5-HT concentration is increased, depressive symptoms are significantly improved[11,12]. In addition, Hama et al[13] also found that the contents of 5-HT, NE, and DA in the frontal lobe and hippocampus of PSD rats were significantly lower than the normal values. A large number of studies have shown that acupuncture treatment can promote the transport of tryptophan in blood and cerebrospinal fluid, promote the synthesis of 5-HT in peripheral blood, thereby significantly increasing the content of monoamine neurotransmitters NE and DA in the brain, especially 5-HT, effectively regulate neurotransmitter levels, repair nerve damage, enhance the expression of nerve factors, enhance nerve excitability, and play a protective role on the central nervous system, to achieve the purpose of treating PSD[14,15]. Acupuncture has been shown in rodent models of PSD to not only increase the concentration of these monoamines but also modulate the expression and affinity of their receptors, thereby enhancing synaptic transmission and exerting antidepressant effects[16,17].

Regulation of amino acid neurotransmitters: Amino acid neurotransmitters have functions such as nourishing nerves and remodeling nerves. Among them, glutamate (Glu) is the most important excitatory amino acid (EAA) neurotransmitter in the central nervous system, while gamma-aminobutyric acid (GABA) is the most important inhibitory amino acid neurotransmitter[18,19]. Studies have found that after stroke, abnormal brain neurotransmitters release EAAs, and EAAs have neuroexcitatory toxic effects, which may cause depression[20]. Glu is one of the EAAs in the central nervous system. Brain tissue damage will lead to an imbalance in the level of Glu in the brain tissue, and the level of inhibitory amino acid neurotransmitter GABA is also disordered[21]. Studies have shown that acupuncture can significantly downregulate the content of Glu and GABA in the hippocampus and caudate putamen, alleviate the nerve damage caused by the accumulation of Glu by reducing inhibitory amino acid neurotransmitters, thereby reducing its toxic damage to the body, relieving the negative emotions of patients and exerting antidepressant effects[21,22].

Regulation of neurotrophic factors

Some scholars have proposed that the neuroimmune system is involved in the pathogenesis of PSD, and brain-derived neurotrophic factor (BDNF) is considered to be the key among them. BDNF is a protein that can promote nerve growth activity and is widely distributed in the nervous system. Tyrosine kinase receptor B (TrkB), as a specific receptor for BDNF, is necessary for the normal differentiation of hippocampal neural progenitor cells. The BDNF-TrkB signaling pathway formed by the combination of the two plays an important role in regulating the growth, differentiation, and apoptosis of nerve cells[23]. Binding of BDNF to TrkB triggers downstream signaling cascades, primarily the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt pathways, which are critical for neuronal survival, differentiation, and most importantly, for the synthesis of proteins required for synaptic plasticity and long-term potentiation[24,25]. After a stroke, patients have varying degrees of brain tissue damage and significant impairment of nerve function. The level of neurotrophic factors such as BDNF in the brain is significantly reduced, which lessens the supportive effect on neurotransmitters such as 5-HT. The excitability of the patient’s nervous system is obviously inhibited, leading to the generation of depressive emotions[26,27]. Studies have found that the expression of BDNF and its receptor TrkB in PSD model rats and in patients with PSD is inhibited, and the serum BDNF content is significantly lower than normal levels[28]. Studies have confirmed that BDNF can promote the development, growth, differentiation, and regeneration of 5-HT and noradrenergic neurons, and acupuncture can increase the content of BDNF in peripheral blood by regulating the BDNF-TrkB signaling pathway, activate the BDNF gene, and further promote the recovery of hippocampal neuron function, thereby promoting the regeneration of the central nervous system, relieving neuropathic diseases, improving the patient's depressive mood, and achieving the purpose of treating PSD[28,29]. Furthermore, animal studies have demonstrated that electroacupuncture (EA) treatment can reverse the decrease in key synaptic plasticity-related proteins, such as postsynaptic density protein 95 and synapsin I, in the hippocampus of PSD model rats[30]. This effect shows a certain “dose dependency” based on treatment duration, underscoring acupuncture's role in repairing damaged synaptic structures and restoring neural network function[31]. Critically, the elevation of BDNF is not merely a mechanistic finding but is strongly correlated with observable clinical improvements. Future studies employing mediation analysis are warranted to quantitatively assess the extent to which BDNF upregulation mediates the reduction in depressive symptoms following acupuncture treatment, thereby strengthening the causal inference between mechanism and outcome[32].

Regulation of neuroendocrine function

Some scholars believe that the occurrence of PSD is related to a disruption in the regulatory function of the hypothalamic-pituitary-adrenal axis (HPA). The HPA axis is a system of direct action and feedback interaction, in which corticotropin-releasing hormone (CRH) is first secreted in the hypothalamus, and CRH promotes the release of adrenocorticotropic hormone (ACTH) when passing through the pituitary gland, and finally acts on the adrenal cortex to synthesize glucocorticoids (mainly cortisol [CORT]). At the same time, the synthesis of CORT will feedback to the pituitary and hypothalamus, and affect the secretion and synthesis of ACTH and CRH, thus forming a feedback pathway[33,34]. When a stroke occurs, if the lesion directly occurs in the hypothalamus, the process of CRH secretion in the hypothalamus of the patient is affected, which will directly lead to HPA axis dysfunction; when the lesion occurs in the hippocampus and other parts that have a greater impact on emotional changes, it is easy to damage the neuroendocrine regulation system, and the patient cannot adjust it by himself, resulting in abnormal hormone secretion in the body, which feedbacks on the HPA axis, leading to its dysfunction[35]. The serum levels of ACTH and CORT in the human body are positively correlated with depressive mood, insomnia, mental anxiety, etc. Hyperfunction of HPA can cause disorder in serum ACTH and CORT levels, leading to the occurrence of PSD[36]. The regulatory effect of acupuncture on the HPA axis is often used to treat various diseases. Acupuncture has been shown to effectively treat PSD by positively influencing the HPA axis. Research indicates that acupuncture helps regulate HPA axis function through multiple mechanisms, including modifying levels of monoamine neurotransmitters, impacting hippocampal activity, and regulating gene expression in the hypothalamus. This benign intervention leads to a reduction in elevated levels of CRH, ACTH, and CORT often observed in PSD rats, thereby improving the behavior of depressive rats, relieving depressive symptoms, and finally achieving the purpose of treating PSD[14,37]. Therefore, inhibiting HPA axis hyperfunction and regulating neuroendocrine function are considered to be one of the mechanisms of acupuncture in the treatment of PSD.

Regulation of inflammatory cytokines

Proinflammatory cytokines involved in the inflammatory response process mainly include interleukin 2 (IL-2), IL-6, and tumor necrosis factor alpha (TNF-α)[38]. After PSD occurs, the activity of the inflammatory signaling pathway p38 MAPK is enhanced and a large number of inflammatory factors are produced. Studies have shown that long-term immune inflammatory reactions will have serious adverse effects on the body's homeostasis, leading to depression or exacerbating cognitive impairment[39]. The significant increase in the level of proinflammatory cytokines activates the inflammatory response, causes an increase in tryptophan metabolism, interferes with the immune level, depletes serum 5-HT, and leads to neurotransmitter disorders. Moreover, immune-inflammatory stress reactions are involved in the occurrence and development of PSD from multiple aspects including the apoptosis of nerve cells (including 5-HT), nerve remodeling, neuroendocrine (HPA), and neurotoxic side effects[40]. Notably, baseline levels of specific inflammatory markers, such as IL-6, may serve as predictive biomarkers for treatment response. Patients with higher pre-treatment inflammatory loads might exhibit a different therapeutic trajectory, and monitoring these cytokines could help stratify patients and personalize acupuncture treatment strategies[41]. Studies have shown that acupuncture can effectively inhibit the activation of the p38 MAPK signaling pathway and significantly reduce the content of proinflammatory cytokines such as IL-2, IL-6, and TNF-α in the serum, alleviate the inflammatory reaction of depression and regulate the edema degree of nerve cells, thereby improving the degree of depression and daily activity ability, to achieve the purpose of treating PSD.

Regulation of oxidative stress injury

Under normal operation of the body, antioxidant enzymes such as superoxide dismutase (SOD) and glutathione (GSH) will quickly clear the oxygen free radicals produced in the body, but when the production of free radicals increases, the body’s antioxidant capacity decreases, and the excessive free radicals in the body cannot be cleared in time, their accumulation in the body will damage the body instead, and this reaction process is oxidative stress[42]. The occurrence of stroke leads to the imbalance of the oxidation and antioxidant system in the patient’s body, and the deficiency of antioxidant enzymes SOD and GSH further enhances the oxidative stress reaction. The hippocampus, frontal lobe, and other brain structures closely related to emotional disorders, which are extremely sensitive to stress reactions, cause neurotoxic reactions and neuronal apoptosis after receiving stimulation, and then lead to the occurrence of PSD[43]. Studies have found that inflammatory reactions can activate oxidative stress reactions, reduce antioxidant enzymes such as SOD and GSH, increase the level of oxidation products, and finally aggravate PSD[35]. Acupuncture can reduce the levels of inflammatory factors such as IL-6 and TNF-α, thereby reversely increasing the plasma levels of SOD and GSH in PSD model rats, reducing oxidative stress damage and correcting the depressive behavior of PSD rats. Therefore, the regulation of oxidative stress damage by acupuncture is a possible mechanism for the treatment of PSD.

Regulation of serum protein levels

Regulation of serum ferritin content: Serum ferritin (SF) is mainly involved in the storage and regulation of iron levels. Stored iron in the body is a strong pro-oxidant, and when excessive iron accumulates in the body, it will form a large number of oxygen free radicals through urging cell reactions. A large number of oxygen free radicals cause oxidative damage to related tissues, leading to the death of some neurons. SF can promote the occurrence and development of depression by triggering oxidative stress reactions[44]. Studies have confirmed that hyperferritinemia has obvious neurotoxicity, and the serum SF content of patients with PSD is in a high-expression state[45]. Clinical studies have found that acupuncture can reduce the serum SF content of patients by mobilizing the body’s anti-inflammatory and antioxidant effects, reduce the damage of SF-mediated oxidative stress to nerve cells, thereby protecting central nerve cells, inhibiting nerve apoptosis, and nervous system degeneration, to effectively improve the patient's depressive symptoms and prevent the occurrence of depression. Therefore, reducing the serum SF level is one of the possible mechanisms of acupuncture in the treatment of PSD.

Regulation of S100B protein concentration: S100B protein is a neurotrophic factor released by astrocytes in the central nervous system and is currently considered a specific protein that can best mark the degree of brain tissue and blood vessel damage[46,47]. Studies have found that the serum S100B protein concentration of patients with PSD is in a high-expression state[48]. Zhang et al[49] found that acupuncture can effectively reduce the serum S100B protein concentration of patients with PSD, reduce the impact of S100B protein on the function of the hippocampus and 5-HT system, and improve the patient's depression while repairing the patient's nerve function. The mechanism of action may be related to acupuncture reducing the serum S100B protein concentration of patients.

Others

Regulation of the brain-gut axis: Studies have shown that damage to the neuroimmune system in patients with PSD will cause intestinal flora disorders and cause intestinal inflammation, which will damage 5-HT signal transduction, thereby leading to aggravation of PSD[40,50]. This bidirectional brain-gut communication pathway connecting brain nerves and intestinal flora is called the “brain-gut axis”. Acupuncture can mediate the “brain-gut axis” pathway by regulating serum 5-HT levels to alleviate the gastrointestinal symptoms of PSD, to achieve the purpose of treating PSD.

Regulation of blood homocysteine level: High homocysteine (Hcy) levels can adversely affect neurotransmitters and cause neurotoxicity by inducing oxidative stress, inflammation, DNA damage, and apoptosis, which are significant risk factors for PSD[51]. Studies have shown that patients with PSD have higher Hcy than those without PSD[52]. Acupuncture has been found to act as an antidepressant through several physiological mechanisms: It regulates Hcy content, affects neurotransmitter secretion, enhances BDNF expression, and suppresses the production of cytokines and inflammation. These combined effects facilitate neuron recovery and improve symptoms of depression.

Research progress on the mechanism of acupuncture treatment for PSD is shown in Table 1. A corresponding schematic diagram (Figure 1) is provided to visually summarize these multi-target mechanisms.

Figure 1 Schematic diagram illustrating the multi-target mechanisms of acupuncture in the treatment of post-stroke depression. 5-HT: 5-hydroxytryptamine; ACTH: Adrenocorticotropic hormone; BDNF: Brain-derived neurotrophic factor; CRH: Corticotropin-releasing hormone; DA: Dopamine; GABA: Gamma-aminobutyric acid; GSH: Glutathione; IL: Interleukin; NE: Norepinephrine; SF: Serum ferritin; SOD: Superoxide dismutase; TNF-α: Tumor necrosis factor alpha.

Table 1 Mechanistic advances in acupuncture for post-stroke depression.

Mechanism category	Specific regulatory targets	Pathological mechanism of PSD	Mechanism of acupuncture action	Ref.
Neurotransmitter regulation	Monoamine neurotransmitters (5-HT, NE, DA)	Brain injury reduces the synthesis of monoamine neurotransmitters, which is negatively correlated with the severity of depression	Promotes tryptophan transport and 5-HT synthesis, increases levels of 5-HT, NE, and DA in the brain, and repairs nerve conduction pathways	[10-14]
	Amino acid neurotransmitters (Glu, GABA)	Brain injury leads to Glu accumulation (neurotoxicity) and GABA imbalance, inducing depression	Downregulates Glu and GABA contents in the hippocampus and caudate putamen, reducing Glu-mediated nerve damage	[15-19]
Neurotrophic factor regulation	BDNF and its receptor TrkB	Post-stroke reduction in BDNF levels inhibits the regeneration of 5-HT neurons, leading to decreased neural excitability	Activates the BDNF-TrkB signaling pathway, increases peripheral blood BDNF content, and promotes the recovery of hippocampal neuron function	[20-24]
Neuroendocrine regulation	HPA axis and CRH, ACTH, CORT	HPA axis hyperfunction increases CRH, ACTH, and CORT levels, which are positively correlated with depression and anxiety	Regulates monoamine neurotransmitters, affects hippocampal function and hypothalamic mRNA expression, reducing CRH, ACTH, and CORT levels	[13,25-29]
Inflammatory cytokine regulation	Proinflammatory cytokines (IL-2, IL-6, TNF-α) and p38 MAPK signaling pathway	Activation of the p38MAPK pathway leads to excessive release of proinflammatory factors, depleting 5-HT and inducing neurotoxicity and depression	Inhibits the activation of the p38MAPK pathway, reduces levels of IL-2, IL-6, and TNF-α, and alleviates neuroinflammation and edema	[30-32]
Oxidative stress regulation	Antioxidant enzymes (SOD, GSH) and oxidative products	Post-stroke imbalance in the oxidation-antioxidation system, reduced SOD and GSH, and accumulation of free radicals leading to neuronal apoptosis	Reduces levels of IL-6 and TNF-α, thereby increasing SOD and GSH contents and alleviating oxidative stress damage	[27,33-35]
Serum protein regulation	SF	High SF induces oxidative stress through iron ions, causing neuronal death and depression	Mobilizes anti-inflammatory and antioxidant effects, reduces SF content, and decreases oxidative damage to nerve cells	[35,36]
	S100B protein	High expression of S100B impairs hippocampal and 5-HT system function, exacerbating depression	Reduces serum S100B concentration, repairs nerve function, and improves depressive mood	[37-39]
Other regulatory mechanisms	Brain-gut axis	Intestinal flora disorder causes intestinal inflammation, disrupting 5-HT signal transduction and aggravating depression	Mediates the brain-gut axis pathway by regulating serum 5-HT levels, alleviating gastrointestinal symptoms	[32,40]
	Blood homocysteine (Hcy)	High Hcy induces depression through inflammation, oxidative stress, and neurotoxicity	Regulates Hcy content to affect neurotransmitter secretion, promotes BDNF expression, inhibits cytokine production, and reduces inflammatory reactions	[41,42]

5-HT: 5-hydroxytryptamine; ACTH: Adrenocorticotropic hormone; BDNF: Brain-derived neurotrophic factor; CRH: Corticotropin-releasing hormone; DA: Dopamine; GABA: Gamma-aminobutyric acid; GSH: Glutathione; Hcy: Homocysteine; HPA: Hypothalamic-pituitary-adrenal; IL: Interleukin; MAPK: Mitogen-activated protein kinase; NE: Norepinephrine; PSD: Post-stroke depression; SF: Serum ferritin; SOD: Superoxide dismutase; TNF-α: Tumor necrosis factor alpha.

CLINICAL ADVANCES IN ACUPUNCTURE FOR PSD

Theoretical framework in TCM

Acupuncture, as a core therapeutic modality within TCM, is based on the theory of meridians and aims to regulate the body’s physiological and pathological states by stimulating specific acupoints[53]. It is widely applied in the treatment of various diseases, including PSD, by promoting the flow of qi and blood, balancing yin and yang, and harmonizing the functions of Zang-fu organs[54].

PSD is categorized as a combined disorder of “stroke” and “depressive syndrome” in TCM. Stroke primarily affects the brain, impairing mental activities, while depressive syndrome originates from liver dysfunction, leading to emotional stagnation. The core pathogenesis involves disharmony of brain shen (spirit) and liver qi stagnation. As stated in Jingyue Quanshu Depressive Syndrome, “Depression due to five qi stagnation can give rise to various diseases” indicating that PSD belongs to “depression secondary to stroke”. Post-stroke qi dysregulation, disharmony of qi-blood-yin-yang, and liver-spleen disharmony lead to phlegm-stasis obstruction of clear orifices, while deficiency of liver-kidney and heart-spleen impairs brain nourishment. This complex pathogenesis features root deficiency (liver-kidney deficiency, heart-spleen qi-blood deficiency) and branch excess (liver qi stagnation, phlegm-stasis obstruction)[14,55].

Critically, the clinical application of acupuncture for PSD demonstrates a favorable safety profile. A recent meta-analysis of high-quality trials indicates that serious adverse events are rare, with minor events such as slight bleeding or hematoma being typically mild and transient[56]. Future studies incorporating structured reporting using CTCAE v5.0 criteria will further strengthen the evidence base for its safety.

Pure acupuncture therapy

Plain needle acupuncture is widely used to alleviate PSD symptoms by regulating shen and smoothing qi flow. Study emphasized regulating shen with Governor Vessel acupoints (Baihui GV20, Yintang EX-HN3, Shenting GV24), combined with liver, spleen, heart, and pericardium meridian points, significantly improving HAMD scores and Barthel Index[57]. Qin et al[58] selected Governing Vessel and Bladder Meridian acupoints (Naohu GV17, Shentang BL44) to activate brain shen, showing marked improvements in depressive and neurological symptoms after 4 weeks. Cai et al[59] integrated shen-regulating (Baihui, Sishencong EX-HN1) and qi-soothing (Taichong LR3, Ganshu BL18) points with Sanyinjiao SP6, demonstrating safe and effective outcomes. Wang et al[60] adopted "Governor Vessel Depression-Treating Acupuncture", using GV20, GV24, EX-HN3, Shuigou GV26 for shen regulation, Hegu LI4-Taichong LR3 to release liver qi, and Neiguan PC6-Shenmen HT7 for mental acuity, effectively relieving depression.

EA therapy

EA combines traditional needling with electrical stimulation, transmitting pulses via peripheral nerves to modulate central pathways. Zhang et al[61] used prefrontal acupoints (Baihui, Yintang, Sishencong, Toulinqi GB15, Shuaigu GB8, Taiyang EX-HN5, Touwei ST8), activating brainstem reticular formation via trigeminal pathways to enhance 5-HT and NA secretion, improving mood and cognition[61]. EA at Fengchi GB20 and Gongxue (extra point) promotes monoamine release through spinal-reticular-brainstem pathways, enhancing cortical excitability via the ascending reticular activating system. Xiao et al[62] found EA at GB20 plus five-element music therapy activated limbic system, improving daily function. Frequency parameters (e.g., dense-sparse waves at 2/15 Hz or 2/100 Hz) show comparable efficacy to antidepressants, with 2/15 Hz demonstrating superior short-term sustainability[63,64]. Optimal frequency for stroke recovery requires further study.

Specialty acupuncture techniques

Scalp acupuncture: Neuroimaging shows limbic-cortico-striato-pallido-thalamic circuits regulate emotion, with prefrontal cortex and limbic system gray matter reduction as key PSD pathologies[65]. Scalp acupuncture directly targets cerebral cortex, upregulating monoamines, neurotrophins, and autophagy to protect neurons[66]. Liu et al[67] used planar needling at bilateral emotional areas and frontal region, activating frontal cortex via cumulative stimulation, safely improving symptoms. Wang et al[68] combined Yu's frontal scalp acupuncture with intradermal needles, forming an "acupuncture field" to activate prefrontal cortex through cluster needling and prolonged retention. Ren[69] applied Jiaoshi scalp acupuncture at bilateral foot motor-sensory and emotional areas with rapid needling, relieving neuronal inhibition and restoring excitability.

Auricular acupuncture: Auricular therapy (transcutaneous auricular vagus nerve stimulation [ta-VNS], auricular pressure, acupuncture) modulates neurohumoral pathways via vagus nerve-nucleus tractus solitarius, promoting neural remodeling[70]. ta-VNS increased 5-HT, BDNF, and cAMP responsive element binding protein 1 (CREB1) in patients with PSD, activating BDNF-CREB signaling for durable antidepressant effects[71]. Magnetic bead auricular pressure regulated transient receptor potential channels, 5-HT, and β-tubulin, reducing neurotoxicity[72]. Applying pressure to specific points on the ear (known as Shenmen, Sympathetic, Heart, Liver, Subcortex) improves a person’s quality of life by modulating default mode network connectivity. Qin-style auricular intradermal needling demonstrated a 93.18% efficacy, with prolonged stimulation and high compliance[73]. The treatment involved needling specific points on the ear corresponding to the spleen, stomach, small intestine, and sympathetic nervous system.

Comprehensive therapies

Acupuncture combined with Chinese herbal medicine: Acupuncture-herb combination targets multi-pathways: Jiang et al[74] combined Chaihu Shugan San with shen-regulating acupuncture, reducing IL-6 and cysteine while increasing BDNF and monoamines, rapidly improving neurofunction. Duan et al[75] used Peiyuan Didan Kaiyu Decoction with Governor Vessel acupuncture, elevating 5-HT and NA in phlegm-stasis PSD. Gong et al[76] combined Danzhi Xiaoyao Powder with Du-Ren meridian acupuncture, increasing Lactobacillus/Bifidobacterium abundance and immune markers.

Acupuncture combined with moxibustion: Moxibustion is a TCM that involves burning dried mugwort (Artemisia vulgaris) to stimulate acupoints with heat[77]. It functions to warm the meridians, dispel cold and dampness, and regulate the flow of qi and blood, thereby supporting neurological recovery and enhancing cortical reorganization after stroke[78] used Huayu Tongluo moxibustion (solid pressing at Baihui, suspending at Dazhui GV14/Shenting) with intradermal needles, improving cognition and quality of life. Leihuo moxibustion at Shenque CV8, Sishencong, Shenmen HT7, Yintang combined with acupuncture reduced IL-2/6 and TNF-α, improving cerebral perfusion[79].

Acupuncture combined with music therapy: Five-element music therapy synergizes with acupuncture to enhance qi resonance. Wang et al[79] used Jue-mode music with GV20/EX-HN3/GV24, elevating 5-HT and improving sleep. Liu et al[80] combined Gong-mode music with acupoints (GV20, Zhongwan CV12, Zusanli ST36), increasing beneficial bacteria and 5-HT, and reducing HAMD-17 and GSRS scores.

Acupuncture combined with rehabilitation training: Psychological rehabilitation corrects negative cognition in PSD. EA plus psychological intervention outperforms single therapy[81]. Acupuncture combined with attribution training improves psychological resilience and neurofunction. Cognitive training during acupuncture establishes positive neural feedback, enhancing long-term outcomes[82]. The comparative efficacy and distinctive advantages of these acupuncture modalities are systematically summarized in Table 2.

Table 2 Comparative efficacy and advantages of acupuncture therapies for post-stroke depression.

Modality	Primary clinical applications and efficacy	Key advantages
Pure acupuncture	Alleviates core depressive symptoms; improves neurological function and daily living activities	Foundation of TCM treatment; addresses both root (deficiency) and branch (excess) causes
Electroacupuncture	Improves mood, cognition, and cortical excitability; offers sustainable short-term results	Combines TCM with electrical neurostimulation for potent effects
Specialty acupuncture techniques
Scalp acupuncture	Targets emotional brain regions; effective for emotional regulation and neuronal recovery	Highly targeted based on neuroimaging; provides sustained stimulation to specific areas
Auricular acupuncture	Provides durable antidepressant effects; improves overall quality of life	Minimally invasive with high compliance; allows for prolonged stimulation (e.g., with beads)
Comprehensive therapies
Acupuncture + herbal medicine	Rapid improvement in neurofunction; addresses complex TCM patterns like phlegm-stasis	Synergistic multi-target approach (anti-inflammatory, neurotrophic, gut microbiome)
Acupuncture + moxibustion	Supports neurological recovery and improves cognitive function	Adds a warming and tonifying effect, ideal for deficiency patterns
Acupuncture + music therapy	Improves mood and sleep; reduces depressive and gastrointestinal symptoms	Holistic approach that integrates sensory stimulation to regulate emotion and physiology
Acupuncture + rehabilitation training	Improves psychological resilience, neurofunction, and long-term outcomes	Integrates physical neuromodulation with behavioral/cognitive training for comprehensive rehab

TCM: Traditional Chinese medicine.

A review of the literature indicates that the antidepressant mechanisms of acupuncture in PSD primarily involve regulating abnormal neurotransmitter levels, inhibiting inflammatory cytokine secretion, increasing neurotrophic factor expression, reducing hippocampal neuronal apoptosis, repairing damaged hippocampal neurons, modulating signaling pathway proteins, and suppressing HPA axis hyperactivity. Compared with Western antidepressant therapy for PSD, acupuncture exhibits a broader regulatory effect, characterized by multi-system, multi-link, multi-level, and multi-target holistic modulation. Acupoint stimulation can influence the functions of multiple organs and systems simultaneously at different biological levels. In pathological states, acupuncture can improve the body's condition, enhance regulatory capacity, induce neuroprotection, and improve the brain tissue's disease resistance, thereby alleviating stroke and post-stroke depressive symptoms.

When evaluating the advantages and limitations of different acupuncture usages, several key points emerge. Manual acupuncture (MA) and EA are the most widely applied techniques. MA allows for individualized manipulation (e.g., reinforcing-reducing methods) tailored to the patient's pattern, but its efficacy is highly dependent on the practitioner's skill[83]. EA offers standardized, quantifiable stimulation parameters, which enhances reproducibility and is particularly advantageous in research settings for investigating specific neurophysiological mechanisms[84]. Scalp acupuncture is often emphasized for stroke-related neurological deficits due to its proposed close connection to the cerebral cortex, while body acupuncture (e.g., targeting LR3, PC6) is more commonly employed for regulating emotional and psychological symptoms[76]. The combination of different techniques, such as MA plus EA or acupuncture combined with moxibustion, may offer synergistic effects[85], although this also increases the complexity of treatment protocols and requires further high-quality evidence.

However, several limitations and unresolved issues exist in the basic research on acupuncture for PSD: The lack of objective and standardized criteria for acupoint selection and treatment, as well as quantitative indicators for needling angle, depth, manipulation, and stimulation intensity, affects the objectivity and reproducibility of experimental results. Therefore, it is necessary to further standardize the quantitative indicators of acupuncture in future studies. Currently, most studies focus on the efficacy of acupuncture in treating PSD, while research on related mechanisms is limited. Thus, basic research on animal models should be strengthened in future studies. The absence of multicenter, large-sample, double-blind controlled trials in clinical research affects the reliability of the results. Therefore, evidence-based medicine should be followed in future clinical studies, and scientific and rigorous large-sample studies should be adopted to make the results more reliable. In particular, future trials should adopt multi-center designs with standardized protocols-using validated scales (e.g., HAMD-17, MADRS) and long-term follow-up (≥ 6 months)-and include subgroup analyses comparing EA with MA. Furthermore, future studies should prioritize standardizing key acupuncture parameters (e.g., needle depth, retention time, and Deqi criteria) through formal expert consensus (e.g., Delphi technique) and implement triple-blind designs to minimize bias and enhance validity. Considering the differences between humans and animals, the conclusions of basic research need to go through clinical transition stages such as exploration, modification, and verification when guiding clinical practice, so that the theories and methods can better guide practical applications.

CONCLUSION

Acupuncture shows multi-target potential for PSD by modulating neurotransmitters, inflammation, neurotrophins, and the HPA axis. Techniques like manual and EA, often combined with moxibustion, can improve depressive symptoms and neurological function. Current limitations include insufficient protocol standardization, overreliance on animal studies, and small clinical trials. Future work should focus on standardizing treatments, using omics to uncover mechanisms, conducting larger trials, and exploring combination and personalized strategies. In conclusion, while acupuncture offers a holistic complementary option for PSD, more robust evidence is needed to confirm its efficacy and support its integration into standard stroke rehabilitation.