Abstract
Comparison of the efficacy of headache reduction between acupuncture, topiramate and botulinum neurotoxin in the prophylaxis of chronic migraine
Mean change of migraine days from baseline. PREEMPT: Phase III Research Evaluating Migraine Prophylaxis Therapy Trial.
Acupuncture is a widely used, non-pharmacological treatment for migraine. Although its use is still controversial, a recent Cochrane systematic review found acupuncture to be as effective as, or possibly more effective than, preventive migraine agents (7). A beneficial effect of acupuncture in migraine prophylaxis was demonstrated in a prospective randomized trial for CM (8). In a 12-week treatment period, a significantly larger decrease in the mean monthly number of moderate/severe headache days was observed in the acupuncture group compared with the topiramate group (−10.5 vs. −7.8 days per 4 weeks, p < 0.01). Significant differences favoring acupuncture across multiple efficacy end points, including mean change of headache days, Migraine Disability Assessment Scores (MIDAS), Hospital Anxiety and Depression Scale (HADS) scores, Short Form 36 (SF-36) scores, Beck Depression Inventory II (BDI-II) scores, mean days of acute medication use, ≥ 50% reduction in monthly moderate/severe headache days, ≥ 50% reduction in monthly headache days, and safety end points were also observed. In the context of the topiramate studies (1,9) and the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials (4–6), similar beneficial effects were also observed in patients who were overusing acute medications.
Does this study identify an alternative choice for CM patients? Probably yes, but the reasons behind the positive effect could be complex. The study was designed according to the guidelines for trials of the prophylactic treatment of CM (10) and had a clearly defined acupuncture treatment procedure following the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations (11), making it possible to replicate the study and provide a basis for comparisons across disciplines. The acupoints chosen are classic acupuncture sites, which correspond to the dermatomal distribution of trigeminocervical complexes: V1 dermatome [Cuanzhu (BL 2) and Yintang (EX-HN 3)], V2 dermatome [Taiyang (EX-HN 5)], and C2 dermatome [Fengchi (GB-20)]. Traditionally, acupuncture has had its own diagnostic system and the acupoints are individualized and tailored for headaches over different meridians. In this study, the benefits from individualized acupuncture are limited by the fixed-site approach. However, even with this trade-off, the acupuncture arm still outweighed the topiramate group. The positive results of this trial seem to provide a rational mechanism linking the intervention with the pathophysiology of migraine; that is, modulating the trigeminal sensory system. While this hypothesis is possible, a second thought is required to interpret the data.
The investigators provided several reasons to justify the choice of topiramate as the active comparator instead of control with sham acupuncture; however, none could offset the putatively higher placebo effect caused by the needling procedure in comparison to oral medication. In addition, the number of physician visits and contact time were remarkably imbalanced between the two arms (24 visits in the acupuncture group vs. six visits in the topiramate group). Physician–patient interaction, especially in a study with such a low drop-out rate (3% in the acupuncture group and 9% in the topiramate group), could have contributed significantly to the observed effect. A double-dummy, placebo-controlled design, that is, verum acupuncture plus oral placebo vs. sham acupuncture plus oral topiramate, might be better to explore the true differences of therapeutic effects between acupuncture and topiramate. However, meta-analysis of previous studies showed that true acupuncture is not superior over sham interventions in migraine prophylaxis (7),which suggested that exact point location could be of limited importance and thus might undermine the success of a double-dummy design. Nonetheless, a recent study suggested that randomized allocation of non-specific acupoints might be able to minimize the treatment effects of sham acupuncture (12).
These study design limitations are not necessarily bad. Although this study could not completely differentiate the difference between needling and topiramate, it conveyed an even more important message: the biological and psychological effects of the twice weekly, fixed-site acupuncture over 3 months is better than topiramate, the only evidence-based oral prophylactic drug for CM. Patients with CM, who desperately need effective treatment, could benefit from the ritual, with hands-on acupuncture therapy and close physician–patient contact. In a recent clinical trial that compared four interventions involving patients with asthma, it was found that three of the interventions – active salbutamol, sham salbutamol and sham acupuncture – were equally effective in controlling asthma symptoms in terms of patient-reported improvement, despite the fact that only the group receiving active salbutamol had objective improvement of forced expiratory volume (FEV1) (13). This study raises the question of whether the patient's subjective perception of being cared for could be a more important outcome measure than objective parameters. This may be truer when confronting headache disorders wherein objective biomarkers are still lacking. Since the only parameter we can rely on is the patient's subjective rating of pain, the physician's ongoing attention may be the greatest benefit.
Are the results generalizable to other populations? Possibly and possibly not. The cultural meaning of an intervention has a significant impact on the placebo effect (and presumably the nocebo effect as well). It is conceivable that the attention of an acupuncturist in Taiwan, perhaps also in China, has a different placebo valence than in another culture, or that the side effects of a tablet has a different nocebo valence (14).
Treatment of CM remains a difficult task and always requires multidisciplinary approaches. As the authors concluded, acupuncture could be considered a treatment option for CM patients willing to undergo this prophylactic treatment, even for those who are overusing acute medications. In addition, it deserves further study to evaluate whether acupuncture as an add-on therapy to topiramate or other prophylactic medications could have additive or synergistic effects on CM.