Fan JQ, Lu WJ, Tan WQ, et al. Effectiveness of acupuncture for anxiety among patients with parkinson disease: a randomized clinical trial. JAMA Netw O. 2022;5(9):e2232133.
To test the effectiveness of acupuncture to reduce anxiety among individuals with Parkinson's disease (PD)
This is an intriguing study performed in China during the height of Covid pandemic. It introduces a new device to explore the efficacy of acupuncture vs sham, and it provides evidence that acupuncture effectively treats anxiety symptoms in patients with Parkinson's disease.
Randomized, double-blinded clinical study using real and sham acupuncture alongside the Hamilton Anxiety Scale (HAM-A) to measure the efficacy of an acupuncture protocol to reduce anxiety
Researchers recruited 105 patients from the Parkinson's clinic of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. Seventy patients met the 5-point inclusion criteria, which required them to be:
- Diagnosed with idiopathic Parkinson's disease;
- Have a PD diagnosis using the Hoehn and Yahr Scale from 1 to 4;
- Assessed for anxiety with scores ranging from 14 to 29 using the HAM-A;
- Able to sign the informed consent; and
- Of an age between 45 to 80 years.
Thirty-five patients were excluded from the study according to the following criteria:
- Diagnosis of cognitive impairment with a score less than 23 on the Montreal Cognitive Assessment;
- Patient had no responsiveness when using high doses of levodopa;
- Drug or alcohol misuse;
- Acupuncture treatment within 30 days of treatment initiation;
- Use of anxiety drugs within 30 days of treatment initiation;
- Major deficiency of neurologic, renal, cardiovascular, or hepatic systems; and
- Intolerance to acupuncture.
Seven others declined due to long travel/distance from home to hospital, and 5 declined due to possible pain caused by acupuncture.
Overall, 34 women and 36 men with a mean age of 61.84 years were enrolled in the study.
An independent mathematician performed a blinded randomization process using SPSS Statistics, version 26.0.
Of the 70 participants, 35 were assigned to receive real acupuncture (RA), and 35 were assigned to receive sham acupuncture (SA). In total, 64 participants finished the 6-week acupuncture protocol and completed a 2-month follow-up study. Ultimately, 6 patients resigned from the study, including: 2 (1 each for RA and SA groups) who became too nervous and had too severe of a tremor during treatment; 1 (SA group) who dropped out due to personal reasons; and 3 (2 from RA group and 1 from SA group) who changed their medication regime of anti-Parkinson drugs, and this altered their suitability for the study criteria.
All RA and SA participants received 8 weeks of acupuncture treatment with 30-minute sessions conducted 3 times per week. Acupuncture points were chosen according to Traditional Chinese Medicine (TCM) theory based on previously published articles related to TCM use with Parkinson's disease and anxiety. The selected treatment protocol included GV24 (shen ting); GV29 (yin tang), bilateral HT7 (shen men); bilateral SP6 (san yin jiao); and Si Shen Zhen (Si Shen Cong), a 4-point area involving GV21, GV19, and 2 bilateral points identified by the research team at approximately 1.5 cun on either side of GV20. Insertion at GV24 and GV29, as well as the 4 needles of Si Shen Zhen, is normally accomplished with the needle shaft angled at a transverse insertion with a depth of 0.5–1.5 cun. For Si Shen Zhen, the 4 needles are directed toward GV20.1
All RA needles were single-use, sterile, and stainless steel with dimensions of 25 mm diameter and 25 mm long, with the exception of SP 6, in which case needles were 40 cm in length. Those in the SA group received treatment using a blunt needle with a “non-insertion procedure,” which was accomplished by use of an experimental device, recently granted a patent by the China National Intellectual Property Administration (No. ZL202121352221.7). This device (see photo) allows a needle to be inserted through a guide tube, which is held securely in place within a pedestal via its sticky base, allowing it to be affixed to the skin. The sham-acupuncture pedestal is made of solid resin and allows insertion of the tube but does not allow penetration of a blunt needle into the skin. The RA pedestal is hollow and allows the needle, inserted through a guide tube, to penetrate skin. Three holes on the pedestal allow guide tubes to be placed at different angles to match the insertion needed for scalp needling. In this study, the researchers established the angle at 15 degrees for all scalp acupoint locations.
Study Parameters Assessed
Researchers noted compliance with Consolidated Standards of Reporting Trials (CONSORT) and the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA).
All patients were taking pharmaceuticals to control symptoms of PD, but the specific drug was not a criterion or impediment to participation. Instead, to ensure equivalency of dose and outcome measures, all medications and doses were converted to a levodopa equivalent to standardize measures and results. Unfortunately, the researchers did not assess these pharmaceuticals within the paper regarding impact on behaviors and other symptoms related to anxiety.
Researchers assessed demographic and clinical characteristics of all participants at baseline before initial treatment.
Researchers measured blood serum levels of adrenocorticotropic hormone (ACTH) and cortisol (CORT) at baseline and at 2 months post clinic treatments. As CORT and ACTH are recognized as influencers of the HPA axis, they are useful for assessing biomarkers, which may reflect a state of anxiety.
This study was designed to assess whether acupuncture reduces anxiety and improves emotional well-being (EW) in Parkinson's disease patients. Researchers employed 3 outcome measures:
- They used the HAM-A to measure aspects of anxiety, mood, emotions, and related somatic experiences.
- They used the Unified Parkinson Disease Rating Scale (UPDRS) and Parkinson Disease Questionnaire (PDQ) to determine changes in daily living activities and assess overall quality-of-life (QOL) changes during the study; and
- They also used the blood serum measures for CORT and ACTH to determine levels of hormones involved with the maintenance of the hypothalamic–pituitary–adrenal axis (HPA).
It is unclear whether patients were required to forego additional acupuncture treatment during the 2-month postclinic phase. Receiving additional acupuncture during this time would impact findings.
Researchers concluded that the efficacy of acupuncture to reduce anxiety in patients with PD becomes more obvious with a time-lapse post-treatment. By the end of the clinical treatment phase (at 8 weeks), outcomes between the RA and SA participants were not statistically significant. The HAM-A measures at the end of the treatment phase were practically identical, with a 0.22 difference (P=0.62). Still, at 8 weeks follow-up to the postclinical phase, RA participants experienced a significant reduction in HAM-A scores over the SA group, for a difference of 7.03 and a P<0.001. Researchers concluded that this measure taken at 8 weeks post-treatment indicates a substantial reduction in anxiety systems among participants from the RA group.
The UPDRS-PDQ39 EW scores among the RA participants were not significantly different than those in the SA group at the end of treatment (–0.25, P=0.62). At 2-month follow-up, the RA group reported improvements above the SA group, with a 2.13% difference (P<0.001), indicating a significantly improved quality-of-life measure in the RA group. At the 8-week follow-up, changes in ACTH and CORT values among participants in the RA group were significant compared to changes noted in the SA group, suggesting that acupuncture potentially inhibits a hyperactive HPA axis. Researchers noted that levels of blood serum ACTH were substantially reduced in the RA group compared to the SA group, subduing activation of the HPA axis and reducing anxiety symptoms.
Dr. Xin Liu reported an affiliation with the patent awarded for the device used to “blind” needle insertion. Funding sources and author disclosures were provided.
Practice Implications & Limitations
This is an exciting study for many reasons, the most obvious one being the timing. Although the authors did not mention this, they conducted the research in-person during a time of extreme medical caution (and perhaps heightened anxiety) amidst the Covid pandemic in China. They also employed a newly patented device for conducting sham acupuncture, with results that suggest it has viability for future research. Researchers additionally identified and embraced implicit bias, presumed to be present with the Chinese participants, as a positive aspect of the study, and they considered the participants ideal candidates to test the legitimacy of SA in this study.
Chinese patients, they explained, have obviously been exposed to RA through normal cultural and medical practices and would, therefore, be more likely to “generally believe that they have received an effective treatment.”2 The authors suggest that all participants were predisposed to placing value on the treatment regardless of RA or SA. They recognized that this same predisposition could impact outcomes if patients feel a strong enough bias that would change their perception of a true outcome. To compensate for this possibility, researchers specifically planned to measure levels of ACTH and CORT hormones at baseline and at 2-month follow-up. Using blood serum biomarkers was determined to be an efficient method to document change, or no change, in rise or fall of 5-HT, a chemical marker of anxiety.
The authors noted that previous research on rats3 indicates that electroacupuncture can inhibit a hyperactive HPA. Although relevant, the 2016 research used electrostimulation at only 2 acupoints (ST36, Zusanli, and CV4, Guanyuan), neither of which were included in the PD protocol.
The authors recognize that further research is needed to explore whether acupuncture can inhibit the HPA axis.
The clinical phase of the study, during which needles were provided 3 times per week, was only 8 weeks in duration, with follow-up scheduled 2 months later. Measures of ACTH and CORT at follow-up document that participants in the RA group experienced lowered ACTH and, thus, reduced 5-HT biomarkers for anxiety, in addition to sustained improvements reported by UPDRS surveys. For the SA group, the combined results of biochemical markers with UPDRS assessments at 8-week follow-up imply that despite assumed bias favoring acupuncture, participants in the SA group were unable to maintain positive biochemical and emotional responses to reduce anxiety levels. Researchers acknowledge that the 8-week duration of the clinical phase was not long enough to lower CORT levels.
The sham-acupuncture pedestal is made of solid resin and allows insertion of the tube but does not allow penetration of a blunt needle into the skin.
Most patients have few options outside of medications for anxiety, which is known to be a common comorbidity of PD. Dated research indicates that anxiety medications, including benzodiazepines, buspirone, and selective serotonin reuptake inhibitors (SSRIs), have various degrees of success in treating anxiety in PD, but they all have side effects that can complicate a patient’s health.4 Attention to the impact of all PD prescriptive medications on states of anxiety and depression among PD patients would have been ideal. Such information would complement clinical understanding of the biochemical response of the blood serum markers of ACTH and CORT during clinic phase and at follow-up.
A few limitations noted by the authors bear consideration. Replicating this study with a diverse ethnic population outside of China is warranted, given the recognized bias of cultural acceptance of acupuncture. They also note that elements of the HAM-A score measuring anxiety are imprecise and need to be better calibrated for patients with PD.
Justification for selection of the acupoints was missing from the article, as was the perspective of TCM’s differential diagnoses related to Parkinson's disease. Perhaps this is understandable, assuming the article was written for publication by the Journal of the American Medical Association and, therefore, the details of a TCM differential diagnosis and acupoint selection would be extraneous to the audience. The question of how and why the acupoints were selected, however, is still a critical piece of information missing from the article.
A 2012 literature review published in CNS Neurosciences and Therapeutics and titled “Acupuncture for anxiety” indicates that the most common acupoints used for anxiety are GV20 (baihu), PC6 (neiguan), HT7 (shen men), SP6 (san yin jiao), and ExHN3 (yin tang).5
Auricular acupuncture (AA) for anxiety has been used as a standard treatment for thousands of years, with some research indicating that a “correct” and extended AA protocol has long-term effects to reduce anxiety over a longer term than body points (Hou, P-W, 2105).6
Although the results presented by the authors are compelling, attention to the function of the selected acupoints as a specific protocol for anxiety in undifferentiated PD would be appropriate in future publications.
Finally, while we celebrate the introduction of and apparent success in using the newly patented sham-acupuncture device, further investigation is needed to explore its efficacy and reliability among different cultures and physical conditions.