Electronic medical databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science were explored to gather clinical studies investigating acupuncture’s impact on anxiety management, with changes in anxiety symptoms as the primary outcomes. The keywords used in each database were (anxi* or nervous* or worry or worried or uneas* or apprehensi* or fret* or angst* or fear* or disquiet* or distress* or stress* or strain*) AND (acupressure or chih-ya or shiatsu or shiatzu or zhi-ya or finger-massage or finger-pressure or Tui-Na). All capturing studies published between February 2014 and July 2023.

Inclusion criteria were formulated using the PICO (Population, Intervention, Context and Outcome) tool (3). The inclusion criteria in this review were as follows:

Studies like animal mechanism endeavors, case reports, self-controlled, non-RCTs, random crossover studies, and quasi-randomized trials were excluded.

Two researchers independently extracted data from the included studies using pre-arranged standardized forms. Extracted data included author information, study designs, sample size, average age of participants, interventions, treatment periods, acupressure points used, experimental and control intervention regimens, outcome measures results, and adverse events. The primary outcome for this review was defined as the change in anxiety level before and immediately after the intervention, evaluated by various scales such as the Visual Analogue Scale for Anxiety (VAS-A), State-Trait Anxiety Inventory (STAI), and many others. Secondary outcomes encompassed measurements such as blood pressure, heart rate, blood oxygen, The Modified Yale Preoperative Anxiety Scale (MYPAS), GAD-7, Quality of Life, and others. Two researchers independently reviewed the searched articles and selected relevant studies, with disagreement resolved through discussions among the research team.

Meta-analysis was conducted only on studies that demonstrated similar clinical characteristics and had no domain rated as high risk according to the Cochrane risk of bias assessment. Heterogeneity among studies was evaluated by calculating the I² statistic and χ² test (assessing the p-value) using Review Manager 5 (V.5.4, The Nordic Cochrane Centre, Copenhagen). Significant heterogeneity was considered when the p-value was <0.10 and I² > 50%, whereupon a random-effects model was employed for data synthesis. The standardised mean differences (SMDs) with 95% CIs were used for continuous outcomes. The overall effect size was calculated based on the pooled SMD, with Cohen’s categories—0.20, 0.50 and 0.80—interpreted as small, medium and large effects, respectively (4).

The methodological quality of identified studies was also assessed according to the quality domains in the Cochrane risk of bias tool. It was used to evaluate the following:

Each domain was rated as “high” (seriously weakens confidence in the results), “unclear” or “low” (unlikely to seriously alter the result). Given the difficulties in blinding the personnel administering acupressure, we only assessed only the blinding of participants and outcome assessments. To follow the guidelines recommended by the Cochrane Back Review Group, a compliance threshold of <50% of the criteria was associated with bias (5). Studies meeting at least four domains without serious flaws were deemed to have a low risk of bias. Disagreements were resolved by discussion or by a third reviewer (HWHT). Where necessary, attempts were made to contact authors for additional information.

This Meta-analysis included 39 RCT articles and a total of 3,395 cases, with 1902 and 1,493 cases in the test and control groups, respectively. The study participants mainly consisted of two categories: healthy individuals and patients. The healthy group included women in labor, parents of children undergoing surgery, military personnel, college students and so on. The patient group included pre-and post-surgical patients, cancer survivors, hemodialysis patients, burns, sports injuries and so on. Anxiety was evaluated using several indicators, including STAI, VAS-A, DASS-42, DASS-21, MAQ, HADS, BSPAS, FAS, POMS-J, Beck Anxiety, BAI, MCDAS, mYPAS, SAQ, GAD-7, PQOL, SAS, GDS, and various physiological parameters. Of these, the STAI and VAS were the most commonly applied (see Table 1).

Twenty-four (6–9, 13, 16, 19, 22–25, 29–32, 44) of the included RCTs were evaluated as having a low risk of bias in the randomization sequence generation, based on detailed description of randomization methods. Sixteen trials (10–12, 14, 15, 17, 18, 20, 21, 26–28, 33–36, 38, 40, 42) lack detailed information, resulting in an unclear risk of bias in randomization. Four trials (6, 15, 17, 40) used open randomization of random numbers table, resulting in a high risk of bias in concealment. Twelve trials (9, 11, 13, 20–23, 28, 33, 39, 41, 43) without sufficient detail were regarded as having an unclear risk of bias in allocation concealment. The remaining trials were evaluated as having a low risk of bias in allocation concealment.

Only one (6) of the 39 studies described the blinding method for outcome evaluators. Eight studies (12, 13, 15, 21, 33, 41, 44, 45) did not describe blinding methods, and five (6, 9, 17, 22, 30) indicated that assessors were not blinded. Six studies (9, 12, 16, 30, 36, 43) exhibited a high risk of data integrity. One trial (19) without sufficient detail was considered as having an unclear risk of bias in allocation concealment. Four studies (8, 11, 14, 15) selectively report results, indicating in a high risk of bias. Other studies (20, 23, 36–38, 40) had registered online with specified outcomes, leading to a low risk of bias in selective reporting. All trials had an unknown risk in other sources of bias. Details of the risk of bias were summarized in Table 2, (Figures 1, 2).

Sensitivity analysis suggested that the main sources of heterogeneity came from the studies of Aygin and Şen (8), Rani et al. (9) and Sharifi Rizi et al. (22), as I² decreased to 51% after their removal (Figure 9). The funnel plot of changes in anxiety levels was symmetric, indicating no detectable publication bias (Figure 4).

Subgroup analysis was conducted to verify whether different interventions in the control group would influence changes in anxiety levels. According to the STAI subgroup analysis, the therapeutic effect of the acupressure group on anxiety levels was higher than that of the sham intervention group and blank control group, with low heterogeneity between groups (I² = 0%, p = 0.77) (Figure 10). Three trials (15, 27, 32) including 133 patients using random effects models demonstrated that acupressure was more effective than sham acupressure in improving changes in anxiety levels (SMD −2.76, 95% CI: −5.98 to 0.46, p = 0.09). Two trials (39, 44) compared acupressure and blank controls in assessing the effect on changes in anxiety levels, but results were significantly different (SMD −3.49, 95% CI: −7.23 to 0.24, p = 0.07).

Anxiety symptoms typically encompass both physical and psychological manifestations such as excessive worry, fatigue, muscle or jaw tension, sleep difficulties, increased heart rate, and sweating. Severe anxiety may also induce symptoms like nausea, headaches, and lack of concentration. To alleviate these symptoms, many individuals resort to use medication including benzodiazepines (45), non-benzodiazepines and anti-anxiety antidepressants, which can potentially lead to side effects and dependency (46, 47). Psychotherapy, through physical and verbal communication, can establish a positive doctor-patient relationship, guiding and aiding patients to alter detrimental behavior habits, cognitive concepts and psychological states (48).

Physical therapy methods such as massage, acupuncture, transcranial magnetic stimulation treatment can also alleviate anxiety and soothe the body and mind. Studies suggest that acupuncture and electroacupuncture can effectively treat anxiety either independently or as adjuncts to pharmacological therapy (49). Acupuncture therapy may reduce preoperative patient anxiety (50). rTMS presents as a feasible therapeutic option for high-prevalence neuropsychiatric dysfunctions and contributes to our understanding of pathological and neuropsychological adaptation processes (51).

Other treatments include practices like yoga, jogging, tai chi and other aerobic exercises, as well as distraction by studying, listening to music, painting, etc., which can all contribute to treating anxiety disorders. Meta-analyses and systematic reviews have shown that these interventions can improve symptoms of depression and anxiety disorders (52).

Acupressure, an ancient nonpharmacological technique used for symptom management, involves the application of steady, gentle pressure on one or more of the body’s 365 energy points across 12 meridians, thereby creating balance and releasing energy. Simple to administer and requiring no instruments, acupressure is suitable for various demographics, from children to the elderly, and can aid in managing clinical symptoms such as dyspnea, pain, insomnia, nausea and vomiting. From a scientific perspective, acupressure aims to influence the sympathetic and parasympathetic systems through pressure application, thereby releasing neurotransmitters and mediators (53), and ultimately relieving anxiety. Studies indicate that acupressure is effective for generalized anxiety disorder and provides lasting benefits (54).

The etiology and pathogenesis of anxiety disorder are complex, believed to involve a variety of factors including genetics, neurobiochemistry, neuroimaging, sex hormones, constitution and other reasons (55–57). Contemporary studies propose that the pathogenesis of anxiety disorder primarily encompasses neurotransmitter hypothesis and neuroendocrine dysfunction hypothesis, specifically the serotonin system, the hypothalamic-pituitary-adrenal (HPA) axis (58), and hypothalamic-pituitary-gonadal (HPG) axis activity (59).

The potential mechanism of acupressure and its treatment of anxiety remains unclear. Most existing literature focuses on general clinical summaries or efficacy observations, and few studies delving into basic research. Acupressure is believed to stimulate specific points on the body, regulating human function, balancing yin and yang, relieving fatigue, and preventing disease (59). The temple can regulate the autonomic nervous system, compensate the heart, and calm the mind. The product of the three yin, involving the liver, spleen, kidney meridians, can have soothing effects. Acupressure massage, grounded in meridian acuity theology, uses massage as the main treatment method, serving as a preventative and therapeutic approach (46). The primary physiological reasons involved in the massage stimulation process might include the stimulation of serotonin to alleviate pain or emotional discomfort and/or expected psychological responses to stress or perceived environmental threats. Acupressure massage has been shown to reduce heart rate, pulse rate and blood pressure by suppressing the sympathetic nerve and activating the parasympathetic nerve, thus relieving anxiety (60).

Mechanism of acupressure on anxiety recent advances in animal models of anxiety, have greatly enhanced our understanding of the potential mechanisms of acupoint therapy in treating anxiety disorders. Four potential mechanisms have been proposed: it may be related to the up-regulation of atrial natriuretic peptide (ANP) expression and downregulation of C-type natriuretic peptide (CNP) expression in the peripheral adrenal medulla, which in turn inhibits the release of corticosterone (CORT) and the activity of hypothalamic-pituitary-adrenal axis (HPA) (61). Acupressure may inhibit the elevation of amygdala-like norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), induced by acute restraint stress (ARS), and prevent the enhancement of tyrosine hydroxylase protein and mRNA expression in the central nucleus of amygdala (CeA) (62). Acupressure can also significantly reduced depressive-like behaviors caused by chronic unpredictable stress (CUS), and the expression of certain NLRP3 and mature IL-1b (63). Lastly, following Tuina, anxiety-like behaviors were efficiently reduced, and the hyperactivity of the HPA axis was efficiently inhibited, along with enhanced GR expression in the hippocampus and lung (64).

Although the effectiveness of acupressure in relieving STAI has been confirmed, the heterogeneity is relatively large. This could be attributed to the wide range of research subjects included in this study, encompassing healthy individuals such as expectant mothers, parents of children awaiting surgery, military personnel, and college students, as well as patients with various pre- and post-surgery, cancer, hemodialysis, burns, sports injuries. However, subgroup analysis did not indicate a decrease in heterogeneity. This could be due to factors such as the choice of acupuncture points and massage duration.

The global spread of COVID-19 has triggered numerous social issues related to health, economy, and society, all of which are important factors contributing to anxiety. To our knowledge, acupressure is a viable method for relieving anxiety. Amid widespread pandemic widespread concerns, acupressure serves massage as a practical treatment strategy with numerous advantages: it is easily implemented, cost-effective, safe, devoid of toxic side effects, and easy acceptance by people readily accepted by different age groups and populations.

Our study benefits from several strengths. Firstly, we focused our review on the effect of acupressure as a standalone treatment, excluding studies involving mixed therapies, and conducted a subgroup study of sham acupressure or blank control in the control group to verify whether acupressure’s effectiveness in treating anxiety. Secondly, our review included 39 RCTS with larger sample sizes and a variety of acupressure points. Compared with previous studies, our study included patients of varying ages, encompassing both diseased and non-diseased populations, thus providing strong evidence supporting the hypothesis that acupressure is effective in treating anxiety. Thirdly, the included studies were conducted at multiple locations and in different countries, covering a diverse range of ethnicities and cultures, potentially reducing selection bias and improving external validity. Fourthly, we conducted sensitivity analysis and funnel plot, indicating that the meta-analysis was stable, robust, and free from publication bias. Lastly, most of the studies were longitudinal, with one having a follow-up period of 1 year, which lends further support to the clinical practice of acupressure in the treatment of patients with anxiety.

However, there are limitations to consider when interpreting these results. This review only included RCTs, thereby excluding observational and non-randomized studies. Most of the included studies did not feature follow-up evaluations, preventing a comprehensive meta-analysis of acupressure’s long-term effects. The overall quality of the studies was low, particularly concerning allocation concealment and participant and personnel blindness. Furthermore, this review only included English-language, excluding potential insights from non-English sources.

Acupressure demonstrates promising application prospects. However, a unified and standardized acupoint selection plan is lacking, and there are limited studies conducting in-depth analyses from an anti-anxiety mechanism perspective. Future research would benefit from a more standardized approach to acupressure point selection, alongside more extensive studies examining the anti-anxiety mechanisms involved.