The long-term effect of acupuncture for patients with chronic tension-type headache: study protocol for a randomized controlled trial

Chronic tension-type headache (CTTH) is a disorder evolving from frequent episodic tension-type headache (TTH), typically bilateral, pressing or tightening in quality, mild to moderate in intensity, lasting hours to days, or unremitting [1]. In April 2016, the World Health Organization reported that chronic headache, occurring on 15 or more days every month affected 1.7–4% of the world’s adult population, among which CTTH, as the most common chronic primary headache disorder, affected 1–3% of adults [2].

According to the guidelines developed by the European Federation of Neurological Societies, prophylactic treatment should be considered in patients with CTTH, and the recommended prophylactic drugs include amitriptyline, mirtazapine, venlafaxine, and muscle relaxants [3]. However, some unpleasant side effects of the recommended drugs have been reported, including sexual dysfunction, body weight changes, gastrointestinal discomfort, unusual bleeding, and bruising [4‐6]. In addition to the serious adverse effects associated with the use of muscle relaxants, its evidence for application to CTTH patients is limited [7]. More importantly, issues such as medication overuse and how to prevent CTTH sufferers from developing medication overuse headache require greater attention.

Acupuncture, one of the most important components in traditional Chinese medicine (TCM), is widely used to relieve tension-type headache [3, 8]. Several trials of good quality have drawn the conclusion that acupuncture was superior to sham acupuncture in TTH treatment [9, 10]; some studies, however, have indicated no significant differences [11‐13]. According to the National Institute for Health and Clinical Excellence clinical guidelines [8] and Cochrane Library systematic reviews [14, 15], acupuncture is recommended for CTTH management. Nevertheless, its scientific basis is still relatively limited owing to a lack of adequate statistical power, insufficient reports, or relevant methodological shortcomings in previous studies [16, 17].

CTTH is a chronic disorder characterized by persistent or recurrent attacks of headaches, thus the long-term effect of acupuncture is of particular importance because of its instant effect in treatments. Therefore, we have designed a randomized controlled trial (RCT) with a 36-week observation period to investigate and evaluate the long-term effect of acupuncture for CTTH.

Previous RCTs have been conducted to explore the effect of acupuncture for TTH compared with no treatment [11, 23], sham interventions (non-skin-penetrating techniques or needling non-acupoints) [9, 11‐13, 16], or other treatment (relaxation, massage, or physiotherapy) [17, 26‐28], but the conclusions remain controversial. In a recent Cochrane systematic review [15], seven of the 12 included trials recruited both episodic and chronic TTH patients [9, 11, 13, 23‐26, 28], which made it relatively difficult to evaluate the effect of acupuncture for CTTH separately and precisely. Three of the 12 trials [16, 17, 27] included participants with CTTH only, but their small sample sizes, various types of acupuncture interventions, non-uniformed comparisons, and different observation periods may lead to an uncertain evaluation of acupuncture effect. Therefore, we designed a two-armed, parallel-design, patient-assessor blind, RCT to explore and evaluate the long-term effect of acupuncture for CTTH treatment. In this trial, we will compare acupuncture with superficial acupuncture to clarify the long-term therapeutic effect of acupuncture for CTTH.

In this trial, participants in different groups will receive treatments in different rooms to block the communication between the two groups and reduce patients’ doubts about different interventions. Moreover, all of the acupuncture manipulations will be performed on the fixed main acupoints by two trained acupuncturists who have passed the special training examination, in order to reduce the influence of participants’ psychological factors on clinical effects. It is reported that negative mood state has a close relationship with TTH [29, 30] Therefore, psychological assessments of participants based on HAMA and HAMD are planned. Furthermore, we will pay special attention to the recording of the deqi sensation, which may enhance the acupuncture effect as described in TCM classical works and traditional acupuncture theory [31].

A placebo control plays a crucial part in evaluating the effectiveness of a treatment, which can help separate the specific and nonspecific effects and reduce bias by enabling blinding. Therefore, being inert and indistinguishable from the true intervention are the main characteristics of a perfect placebo or a sham intervention. However, to devise or find adequate placebos seems too difficult for physical interventions, such as acupuncture. Currently, superficial acupuncture is considered as a type of sham acupuncture, because the needle depth does not reach acupoints’ anatomical layers. However, there is increasing evidence that sham acupuncture might be associated with larger placebo effects than pharmacological placebos [32‐34], especially for some subjective outcomes and the treatment of pain [35]. A positive expectation of an intervention is an important part of the placebo effect [36, 37], which is also supported by many previous trials [38‐41]. In addition, a good doctor-patient relationship also contributes to patients’ expectations, which may increase placebo effects after repeated treatments and harmonious communications [42]. It may be the reason why no significant differences of effects between acupuncture and sham acupuncture were reported by several trials [11‐13, 24]. Hence, we will make a comparison of participants’ expectations between two groups to eliminate the impact on our results.

A recent RCT reported that the acupuncture effect can be maintained for 20 weeks after 20 sessions of treatment over 4 weeks, which could be considered as powerful evidence for the existence of a sustained effect produced by acupuncture [43]. In addition, a systematic review indicated that the placebo effect of acupuncture showed a unique pattern according to time, which increased from baseline to 12 weeks and decreased after 12 weeks [44]. Considering the necessity of a relatively long observation period, we will conduct the trial over a period of 36 weeks and make assessments every 4 weeks, which aims to not only evaluate the long-term effect of acupuncture for CTTH, but also distinguish curative effects from placebo effects of acupuncture. However, the long observation period has its limitations. It may increase the rate of patient dropout and we will not know if the patients receive other treatments in the follow-up period. To minimize the potential bias, we formulate the plan to reduce dropout by establishing good communication relationships with participants and maintaining close contacts via telephone calls, text messages and emails during the follow-up period. Moreover, characteristics of the dropouts will be extracted and analyzed, which can help judge whether the results are affected by the bias.

In conclusion, the results of this trial are expected to not only provide clinical evidence of the effectiveness of acupuncture as a painkiller, but also evaluate the duration and intensity of the acupuncture effect for CTTH.