Headache Currents
HEADACHE CURRENTS
Acupuncture for Migraine Prevention Arnaldo Neves Da Silva, MD
Background.—Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture. Methods.—Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body. Results.—This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications. Conclusion.—Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients’ recovery. Key words: acupuncture, prevention, alternative medicine
Acupuncture originated in China over 3000 years ago and is one of the oldest healing practices known to modern civilization. It is routine practice in Asian countries and to some extent a popular practice worldwide. It has a long tradition for the treatment of different pain conditions including headaches.1 Acupuncture is a broad term describing an array of procedures that stimulate anatomical points of the body using diverse techniques such as penetrating the skin with solid metallic needles that are stimulated by hands or electrical devices. The exact mechanism by which acupuncture may relieve pain and therefore migraine pain is not entirely understood, although research evidence suggests that acupuncture may suppress the nociceptive trigeminal nucleus caudalis and spinal dorsal horn neurons via modulation of the release of neuropeptides and neurotransmitters.2,3 In traditional Chinese medicine (TCM), the body is seen as a balance of 2 inseparable forces, Yin and Yang, and health is achieved by maintaining the body in a balanced state.4 Each organ in the body has an element of Yin and Yang within it. Even From MHNI (Michigan Head Pain and Neurological Institute), Ann Arbor, MI, USA. Address all correspondence to A.N. Da Silva, A.N. Da Silva, 3120 Professional Drive, Ann Arbor, MI, 48104 USA. Accepted for publication January 7, 2014. ............. Headache © 2015 American Headache Society
though an organ may be predominantly Yin or Yang, the balance is maintained throughout the body, because the sum total of Yin and Yang must be in equilibrium. Yin refers to feminine aspects of life including night, peace, wet, cold, winter, small, and solid. Yang refers to masculine aspects of life including day, anger, dry, hot, summer, large, and hollow. Other concepts in TCM include Qi, the vital energy that circulates inside the meridians and supports every life process and organic function including blood flow. Zang and Fu, an additional 2 characteristics, are also divided among the internal organs. Zang organs include the heart, liver, spleen, lungs, and kidneys, organs that transform and store the essential Qi. Fu organs include the gallbladder, stomach, large and small intestines, and bladder, organs whose major function is digestion and excretion. The Jing Luo meridian network consists of major meridians (Jin channels) and minor meridians (Luo collaterals) distributed throughout the body. Inside the meridians, Qi flows continuously.3 In 1996, the United States Food Administration changed the classification of acupuncture needles from class III (experimental) to class II (non-experimental but regulated) medical devices allowing their use in clinical practice.5 This review will consider the Cochrane Review on acupuncture, head to head studies, and large prospective trials, then make some clinical conclusions. The small number of studies limits certitude on acupuncture effectiveness, confirmed by the Cochrane meta-analysis.
COCHRANE REVIEW A meta-analysis of 22 trials with 4419 subjects published in 2009 addressed the effectiveness of acupuncture for migraine prevention. Six trials showed that after 3-4 months, acupuncture is superior to basic care (usually acute care only). Fourteen trials compared “true” acupuncture to “sham” acupuncture, and the pooled analysis failed to demonstrate a statistically significant superiority of true acupuncture in any outcome measures, but both groups had fewer headaches than before treatment. Four trials compared acupuncture to drugs that were proven as migraine preventives, and the acupuncture group had a slightly better outcome with fewer adverse effects than the prophylactic drugs. Overall, the authors concluded that patients can benefit from acupuncture, but it seems that correct needle placement is less important than believed by acupuncturists, as the sham and traditional acupuncture effects were comparable.6 ............. Conflict of Interest: A.N. Da Silva is on the speakers bureau for Depomed. Financial Support: None.
470
471 | Headache | March 2015
HEAD TO HEAD STUDIES Facco et al randomized 100 patients into 2 groups of 50 each. Group A received 20 sessions of acupuncture, and group B 600 mg of valproic acid per day. Rizatriptan 10 mg orally dissolvable tablets were allowed to acutely treat headache attacks. The study reported reduced pain intensity and lower rizatriptan intake at 6 months follow-up with no adverse events in the acupuncture group.7 Yang and colleagues compared acupuncture with topiramate in migraine prophylaxis. Sixty-six patients were randomized into 2 groups. The acupuncture group had 24 treatments over 12 weeks and the topiramate group was started on 25 mg and increased by 25 mg/day per week over 4 weeks to 100 mg/day followed by an 8-week maintenance period. There was a significantly larger decrease in the mean monthly number of moderate/ severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (P < .01). Adverse effects occurred in 6% in the acupuncture group and 66% in the topiramate group.8 Streng et al assessed the effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis. Fifty-nine patients were randomized to acupuncture (8-15 sessions) and 55 to metoprolol (100-200 mg daily). The metoprolol group had a much higher drop-out rate (18 vs 2). This was a negatives study, as in the acupuncture group, the number of migraine days decreased by 2.5 ± 2.9 days (baseline 5.8 ± 2.5 days) compared with 2.2 ± 2.7 days (baseline 5.8 ± 2.9 days) in the metoprolol group (P = .721). However, the responder rate, the proportion of responders with reduction of migraine attacks by ≥ 50%, was 61% for acupuncture and 49% for metoprolol. The study was powered for 480 subjects, but missing only 114 patients were enrolled, and there was a high drop-out rate in the metoprolol group, suggesting caution in interpretation of the results.9 Allais et al compared acupuncture with flunarizine, a migraine preventive agent not available in the United States, but used widely in the rest of the world. Eighty women with migraines were assigned to acupuncture weekly for 2 months and then once/month for 4 months. A second group of 80 women with migraine were assigned to use 10 mg daily of flunarizine for 2 months and then 20 mg for 4 months. Frequency of migraine attacks and use of abortives was considerably lower in both groups, but at 2 and 4 months of therapy, the number of attacks was lower in the acupuncture group. At 6 months, there was no difference between the 2 groups, but pain intensity and adverse effects were lower in the acupuncture group.10
LARGE TRIALS Linde et al investigated the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in migraineurs. Three hundred and eight subjects were randomized
Headache Currents in to 3 groups: acupuncture group, sham acupuncture group, and waiting list control. In the acupuncture and sham acupuncture groups, patients received 12 treatments over 8 weeks. The main outcome measure was the difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization. Between baseline and weeks 9 to 12, the mean (standard deviation) number of headache days decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline 5.0 (2.4) days in the sham acupuncture group and by 0.8 (2.0) days from a baseline of 5.4 (3.0) in the no acupuncture group. Reduction in number of headache days by at least 50% was observed in 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group. The study conclusion was that acupuncture was not more effective than sham acupuncture in headache prevention, although both interventions were more effective than a waiting list group.11 Diener and colleagues conducted a prospective, randomized, multicenter, double-blind, parallel-group, controlled trial including patients with 2 to 6 migraine attacks per month randomly assigned to verum acupuncture (N = 313), sham acupuncture (n = 339), and standard therapy (n = 308). Immediately after randomization, 125 patients withdrew from the study, 106 from the standard therapy alone, certainly caused by disappointment of not being randomized to the acupuncture groups. Patients received 10 sessions of acupuncture in 6 weeks or continuous prophylaxis with drugs (β-blockers, calcium-channel blockers, or anticonvulsants). The primary outcome was the difference in migraine days between 4 weeks before randomization and 23-26 weeks after randomization, and it showed a mean reduction of 2.3 days (95% confidence interval 1.9-2.7) in the verum acupuncture group, 1.5 days (95% confidence interval 1.1-2.0) in the sham acupuncture group, and 2.1 days (95% confidence interval 1.5-2.7) in the standard therapy group. These numbers were statistically significant compared with baseline (P < .0001), but not across the treatment groups (P = .09). At 26 weeks after randomization, the proportion of responders defined as reduction of migraine days by at least 50% was 47% in the verum group, 39% in the sham group, and 40% in the standard therapy group (P = .133). The authors concluded that the treatment outcomes did not differ between groups.12 Jena et al conducted a large trial to investigate the effectiveness of acupuncture in addition to routine care in patients with primary headaches (migraine and tension-type headaches) compared with routine care alone, and whether acupuncture results differed in randomized and non-randomized patients. In a randomized controlled trial plus non-randomized cohort, patients with headaches were allocated to receive up to 15 acupuncture sessions over 3 months or to a control group receiving no acupuncture during the first 3 months. Number of headache days, pain intensity, and health-related quality of life (SF-36) were assessed at baseline and after 3 and 6 months using standardized
472 | Headache | March 2015
questionnaires. At 3 months, the number of headache days decreased from 8.4 ± 7.2 to 4.7 ± 5.6 in the acupuncture group and from 8.1 ± 6.8 to 7.5 ± 6.3 in the control group (P < .001). Improvement of pain and quality of life were also statistically significant in the acupuncture group (P < .001). Treatment success was maintained at 6 months, outcomes were similar in randomized and non-randomized patients, and hence the authors concluded that acupuncture plus routine care in patient with headaches was associated with marked clinical improvement compared with routine care alone.13 Li et al assessed the efficacy of migraine-specific acupuncture points, randomizing 480 patients with migraine into 4 groups: Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture, and sham acupuncture (control). Shaoyang is a lateral headache according to acupuncture theory. All groups received 20 treatments that included electrical stimulation over 4 weeks. Patients in the acupuncture groups reported fewer headache days than the control group during weeks 5-8 and 13-16. There was a significant but not clinically relevant benefit for almost all secondary outcomes in the 3 acupuncture groups compared with the control group. There was no significant difference between the 3 acupuncture groups. The authors concluded that acupuncture appears to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.14
CONCLUSIONS Acupuncture is effective for chronic pain management, and significant although modest differences between true and sham acupuncture suggest that acupuncture effect in headache is likely more than a placebo.15 A well-designed, multicenter, randomized trial well powered with 480 patients failed to demonstrate a convincing superiority of acupuncture over sham acupuncture in migraine prophylaxis.14 Complicating certain conclusions, Meissner et al, analyzing results of 79 randomized clinical trials of migraine prophylaxis, concluded that sham acupuncture and sham surgery are associated with higher responder rates than oral pharmacological placebos.16 A meta-analysis of placebo response in the prophylaxis of migraine that including 32 clinical trials estimated the placebo response in 21% and 30% of the patients who took placebo reported some adverse effect.17 The therapeutic gain for most drugs or alternative treatments compared with placebo in terms of difference in efficacy is small.18 Acupuncture is probably at least as effective as conventional drug preventive therapy for migraine and is safe, long lasting, and may be cost-effective.19 Cost effectiveness of acupuncture in migraine prophylaxis was validated by Witt et al in a randomized controlled trial.20
Headache Currents Acupuncture is a complex intervention that may also depend on the relationship built between therapist and patient to exert a positive effect in patient recovery.4
References 1. Gaul C, Eismann R, Schmidt T, et al. Use of complementary and alternative medicine in patients suffering from primary headache disorders. Cephalalgia. 2009;29:1069-1078. 2. Sheng LL, Nishiyama K, Honda T, Sugiura M, Yaginuma H, Sugiura Y. Suppressive effects of neiting acupuncture on toothache: An experimental analysis on fos expression evoked by tooth pulp stimulation in the trigeminal subnucleus pars caudalis and the periaqueductal gray of rats. Neurosci Res. 2000;38:331-339. 3. Zhao CH, Stillman MJ, Rozen TD. Traditional and evidence-based acupuncture in headache management: Theory, mechanism, and practice. Headache. 2005;45:716-730. 4. Schiapparelli P, Allais G, Rolando S, et al. Acupuncture in primary headache treatment. Neurol Sci. 2011;32(Suppl. 1):S15-S18. 5. Eskinazi DP, Jobst KA. National institutes of health office of alternative medicine-food and drug administration workshop on acupuncture. J Altern Complement Med. 1996;2:3-6. 6. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009;(1):CD001218. doi: 10.1002/14651858. 7. Facco E, Liguori A, Petti F, Fauci AJ, Cavallin F, Zanette G. Acupuncture versus valproic acid in the prophylaxis of migraine without aura: A prospective controlled study. Minerva Anestesiol. 2013;79:634-642. 8. Yang CP, Chang MH, Liu PE, et al. Acupuncture versus topiramate in chronic migraine prophylaxis: A randomized clinical trial. Cephalalgia. 2011;31:1510-1521. 9. Streng A, Linde K, Hoppe A, et al. Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis. Headache. 2006;46:1492-1502. 10. Allais G, De Lorenzo C, Quirico PE, et al. Acupuncture in the prophylactic treatment of migraine without aura: A comparison with flunarizine. Headache. 2002;42:855-861. 11. Linde K, Streng A, Jurgens S, et al. Acupuncture for patients with migraine: A randomized controlled trial. JAMA. 2005;293:21182125. 12. Diener HC, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: A multicentre randomised controlled clinical trial. Lancet Neurol. 2006;5:310-316. 13. Jena S, Witt CM, Brinkhaus B, Wegscheider K, Willich SN. Acupuncture in patients with headache. Cephalalgia. 2008;28:969979. 14. Li Y, Zheng H, Witt CM, et al. Acupuncture for migraine prophylaxis: A randomized controlled trial. CMAJ. 2012;184:401410. 15. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med. 2012;172:1444-1453. 16. Meissner K, Fassler M, Rucker G, et al. Differential effectiveness of placebo treatments: A systematic review of migraine prophylaxis. JAMA Intern Med. 2013;173:1941-1951.
473 | Headache | March 2015
17. Macedo A, Banos JE, Farre M. Placebo response in the prophylaxis of migraine: A meta-analysis. Eur J Pain. 2008;12:68-75. 18. Diener HC. Acupuncture prophylaxis of migraine no better than sham acupuncture for decreasing frequency of headaches. Evid Based Med. 2013;18:33-34.
Headache Currents 19. Molsberger A. The role of acupuncture in the treatment of migraine. CMAJ. 2012;184:391-392. 20. Witt CM, Reinhold T, Jena S, Brinkhaus B, Willich SN. Costeffectiveness of acupuncture treatment in patients with headache. Cephalalgia. 2008;28:334-345.
HEADACHE CURRENTS
Acupuncture for Migraine Prevention Arnaldo Neves Da Silva, MD
Background.—Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture. Methods.—Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body. Results.—This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications. Conclusion.—Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients’ recovery. Key words: acupuncture, prevention, alternative medicine
Acupuncture originated in China over 3000 years ago and is one of the oldest healing practices known to modern civilization. It is routine practice in Asian countries and to some extent a popular practice worldwide. It has a long tradition for the treatment of different pain conditions including headaches.1 Acupuncture is a broad term describing an array of procedures that stimulate anatomical points of the body using diverse techniques such as penetrating the skin with solid metallic needles that are stimulated by hands or electrical devices. The exact mechanism by which acupuncture may relieve pain and therefore migraine pain is not entirely understood, although research evidence suggests that acupuncture may suppress the nociceptive trigeminal nucleus caudalis and spinal dorsal horn neurons via modulation of the release of neuropeptides and neurotransmitters.2,3 In traditional Chinese medicine (TCM), the body is seen as a balance of 2 inseparable forces, Yin and Yang, and health is achieved by maintaining the body in a balanced state.4 Each organ in the body has an element of Yin and Yang within it. Even From MHNI (Michigan Head Pain and Neurological Institute), Ann Arbor, MI, USA. Address all correspondence to A.N. Da Silva, A.N. Da Silva, 3120 Professional Drive, Ann Arbor, MI, 48104 USA. Accepted for publication January 7, 2014. ............. Headache © 2015 American Headache Society
though an organ may be predominantly Yin or Yang, the balance is maintained throughout the body, because the sum total of Yin and Yang must be in equilibrium. Yin refers to feminine aspects of life including night, peace, wet, cold, winter, small, and solid. Yang refers to masculine aspects of life including day, anger, dry, hot, summer, large, and hollow. Other concepts in TCM include Qi, the vital energy that circulates inside the meridians and supports every life process and organic function including blood flow. Zang and Fu, an additional 2 characteristics, are also divided among the internal organs. Zang organs include the heart, liver, spleen, lungs, and kidneys, organs that transform and store the essential Qi. Fu organs include the gallbladder, stomach, large and small intestines, and bladder, organs whose major function is digestion and excretion. The Jing Luo meridian network consists of major meridians (Jin channels) and minor meridians (Luo collaterals) distributed throughout the body. Inside the meridians, Qi flows continuously.3 In 1996, the United States Food Administration changed the classification of acupuncture needles from class III (experimental) to class II (non-experimental but regulated) medical devices allowing their use in clinical practice.5 This review will consider the Cochrane Review on acupuncture, head to head studies, and large prospective trials, then make some clinical conclusions. The small number of studies limits certitude on acupuncture effectiveness, confirmed by the Cochrane meta-analysis.
COCHRANE REVIEW A meta-analysis of 22 trials with 4419 subjects published in 2009 addressed the effectiveness of acupuncture for migraine prevention. Six trials showed that after 3-4 months, acupuncture is superior to basic care (usually acute care only). Fourteen trials compared “true” acupuncture to “sham” acupuncture, and the pooled analysis failed to demonstrate a statistically significant superiority of true acupuncture in any outcome measures, but both groups had fewer headaches than before treatment. Four trials compared acupuncture to drugs that were proven as migraine preventives, and the acupuncture group had a slightly better outcome with fewer adverse effects than the prophylactic drugs. Overall, the authors concluded that patients can benefit from acupuncture, but it seems that correct needle placement is less important than believed by acupuncturists, as the sham and traditional acupuncture effects were comparable.6 ............. Conflict of Interest: A.N. Da Silva is on the speakers bureau for Depomed. Financial Support: None.
470
471 | Headache | March 2015
HEAD TO HEAD STUDIES Facco et al randomized 100 patients into 2 groups of 50 each. Group A received 20 sessions of acupuncture, and group B 600 mg of valproic acid per day. Rizatriptan 10 mg orally dissolvable tablets were allowed to acutely treat headache attacks. The study reported reduced pain intensity and lower rizatriptan intake at 6 months follow-up with no adverse events in the acupuncture group.7 Yang and colleagues compared acupuncture with topiramate in migraine prophylaxis. Sixty-six patients were randomized into 2 groups. The acupuncture group had 24 treatments over 12 weeks and the topiramate group was started on 25 mg and increased by 25 mg/day per week over 4 weeks to 100 mg/day followed by an 8-week maintenance period. There was a significantly larger decrease in the mean monthly number of moderate/ severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (P < .01). Adverse effects occurred in 6% in the acupuncture group and 66% in the topiramate group.8 Streng et al assessed the effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis. Fifty-nine patients were randomized to acupuncture (8-15 sessions) and 55 to metoprolol (100-200 mg daily). The metoprolol group had a much higher drop-out rate (18 vs 2). This was a negatives study, as in the acupuncture group, the number of migraine days decreased by 2.5 ± 2.9 days (baseline 5.8 ± 2.5 days) compared with 2.2 ± 2.7 days (baseline 5.8 ± 2.9 days) in the metoprolol group (P = .721). However, the responder rate, the proportion of responders with reduction of migraine attacks by ≥ 50%, was 61% for acupuncture and 49% for metoprolol. The study was powered for 480 subjects, but missing only 114 patients were enrolled, and there was a high drop-out rate in the metoprolol group, suggesting caution in interpretation of the results.9 Allais et al compared acupuncture with flunarizine, a migraine preventive agent not available in the United States, but used widely in the rest of the world. Eighty women with migraines were assigned to acupuncture weekly for 2 months and then once/month for 4 months. A second group of 80 women with migraine were assigned to use 10 mg daily of flunarizine for 2 months and then 20 mg for 4 months. Frequency of migraine attacks and use of abortives was considerably lower in both groups, but at 2 and 4 months of therapy, the number of attacks was lower in the acupuncture group. At 6 months, there was no difference between the 2 groups, but pain intensity and adverse effects were lower in the acupuncture group.10
LARGE TRIALS Linde et al investigated the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in migraineurs. Three hundred and eight subjects were randomized
Headache Currents in to 3 groups: acupuncture group, sham acupuncture group, and waiting list control. In the acupuncture and sham acupuncture groups, patients received 12 treatments over 8 weeks. The main outcome measure was the difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization. Between baseline and weeks 9 to 12, the mean (standard deviation) number of headache days decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline 5.0 (2.4) days in the sham acupuncture group and by 0.8 (2.0) days from a baseline of 5.4 (3.0) in the no acupuncture group. Reduction in number of headache days by at least 50% was observed in 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group. The study conclusion was that acupuncture was not more effective than sham acupuncture in headache prevention, although both interventions were more effective than a waiting list group.11 Diener and colleagues conducted a prospective, randomized, multicenter, double-blind, parallel-group, controlled trial including patients with 2 to 6 migraine attacks per month randomly assigned to verum acupuncture (N = 313), sham acupuncture (n = 339), and standard therapy (n = 308). Immediately after randomization, 125 patients withdrew from the study, 106 from the standard therapy alone, certainly caused by disappointment of not being randomized to the acupuncture groups. Patients received 10 sessions of acupuncture in 6 weeks or continuous prophylaxis with drugs (β-blockers, calcium-channel blockers, or anticonvulsants). The primary outcome was the difference in migraine days between 4 weeks before randomization and 23-26 weeks after randomization, and it showed a mean reduction of 2.3 days (95% confidence interval 1.9-2.7) in the verum acupuncture group, 1.5 days (95% confidence interval 1.1-2.0) in the sham acupuncture group, and 2.1 days (95% confidence interval 1.5-2.7) in the standard therapy group. These numbers were statistically significant compared with baseline (P < .0001), but not across the treatment groups (P = .09). At 26 weeks after randomization, the proportion of responders defined as reduction of migraine days by at least 50% was 47% in the verum group, 39% in the sham group, and 40% in the standard therapy group (P = .133). The authors concluded that the treatment outcomes did not differ between groups.12 Jena et al conducted a large trial to investigate the effectiveness of acupuncture in addition to routine care in patients with primary headaches (migraine and tension-type headaches) compared with routine care alone, and whether acupuncture results differed in randomized and non-randomized patients. In a randomized controlled trial plus non-randomized cohort, patients with headaches were allocated to receive up to 15 acupuncture sessions over 3 months or to a control group receiving no acupuncture during the first 3 months. Number of headache days, pain intensity, and health-related quality of life (SF-36) were assessed at baseline and after 3 and 6 months using standardized
472 | Headache | March 2015
questionnaires. At 3 months, the number of headache days decreased from 8.4 ± 7.2 to 4.7 ± 5.6 in the acupuncture group and from 8.1 ± 6.8 to 7.5 ± 6.3 in the control group (P < .001). Improvement of pain and quality of life were also statistically significant in the acupuncture group (P < .001). Treatment success was maintained at 6 months, outcomes were similar in randomized and non-randomized patients, and hence the authors concluded that acupuncture plus routine care in patient with headaches was associated with marked clinical improvement compared with routine care alone.13 Li et al assessed the efficacy of migraine-specific acupuncture points, randomizing 480 patients with migraine into 4 groups: Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture, and sham acupuncture (control). Shaoyang is a lateral headache according to acupuncture theory. All groups received 20 treatments that included electrical stimulation over 4 weeks. Patients in the acupuncture groups reported fewer headache days than the control group during weeks 5-8 and 13-16. There was a significant but not clinically relevant benefit for almost all secondary outcomes in the 3 acupuncture groups compared with the control group. There was no significant difference between the 3 acupuncture groups. The authors concluded that acupuncture appears to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.14
CONCLUSIONS Acupuncture is effective for chronic pain management, and significant although modest differences between true and sham acupuncture suggest that acupuncture effect in headache is likely more than a placebo.15 A well-designed, multicenter, randomized trial well powered with 480 patients failed to demonstrate a convincing superiority of acupuncture over sham acupuncture in migraine prophylaxis.14 Complicating certain conclusions, Meissner et al, analyzing results of 79 randomized clinical trials of migraine prophylaxis, concluded that sham acupuncture and sham surgery are associated with higher responder rates than oral pharmacological placebos.16 A meta-analysis of placebo response in the prophylaxis of migraine that including 32 clinical trials estimated the placebo response in 21% and 30% of the patients who took placebo reported some adverse effect.17 The therapeutic gain for most drugs or alternative treatments compared with placebo in terms of difference in efficacy is small.18 Acupuncture is probably at least as effective as conventional drug preventive therapy for migraine and is safe, long lasting, and may be cost-effective.19 Cost effectiveness of acupuncture in migraine prophylaxis was validated by Witt et al in a randomized controlled trial.20
Headache Currents Acupuncture is a complex intervention that may also depend on the relationship built between therapist and patient to exert a positive effect in patient recovery.4
References 1. Gaul C, Eismann R, Schmidt T, et al. Use of complementary and alternative medicine in patients suffering from primary headache disorders. Cephalalgia. 2009;29:1069-1078. 2. Sheng LL, Nishiyama K, Honda T, Sugiura M, Yaginuma H, Sugiura Y. Suppressive effects of neiting acupuncture on toothache: An experimental analysis on fos expression evoked by tooth pulp stimulation in the trigeminal subnucleus pars caudalis and the periaqueductal gray of rats. Neurosci Res. 2000;38:331-339. 3. Zhao CH, Stillman MJ, Rozen TD. Traditional and evidence-based acupuncture in headache management: Theory, mechanism, and practice. Headache. 2005;45:716-730. 4. Schiapparelli P, Allais G, Rolando S, et al. Acupuncture in primary headache treatment. Neurol Sci. 2011;32(Suppl. 1):S15-S18. 5. Eskinazi DP, Jobst KA. National institutes of health office of alternative medicine-food and drug administration workshop on acupuncture. J Altern Complement Med. 1996;2:3-6. 6. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009;(1):CD001218. doi: 10.1002/14651858. 7. Facco E, Liguori A, Petti F, Fauci AJ, Cavallin F, Zanette G. Acupuncture versus valproic acid in the prophylaxis of migraine without aura: A prospective controlled study. Minerva Anestesiol. 2013;79:634-642. 8. Yang CP, Chang MH, Liu PE, et al. Acupuncture versus topiramate in chronic migraine prophylaxis: A randomized clinical trial. Cephalalgia. 2011;31:1510-1521. 9. Streng A, Linde K, Hoppe A, et al. Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis. Headache. 2006;46:1492-1502. 10. Allais G, De Lorenzo C, Quirico PE, et al. Acupuncture in the prophylactic treatment of migraine without aura: A comparison with flunarizine. Headache. 2002;42:855-861. 11. Linde K, Streng A, Jurgens S, et al. Acupuncture for patients with migraine: A randomized controlled trial. JAMA. 2005;293:21182125. 12. Diener HC, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: A multicentre randomised controlled clinical trial. Lancet Neurol. 2006;5:310-316. 13. Jena S, Witt CM, Brinkhaus B, Wegscheider K, Willich SN. Acupuncture in patients with headache. Cephalalgia. 2008;28:969979. 14. Li Y, Zheng H, Witt CM, et al. Acupuncture for migraine prophylaxis: A randomized controlled trial. CMAJ. 2012;184:401410. 15. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med. 2012;172:1444-1453. 16. Meissner K, Fassler M, Rucker G, et al. Differential effectiveness of placebo treatments: A systematic review of migraine prophylaxis. JAMA Intern Med. 2013;173:1941-1951.
473 | Headache | March 2015
17. Macedo A, Banos JE, Farre M. Placebo response in the prophylaxis of migraine: A meta-analysis. Eur J Pain. 2008;12:68-75. 18. Diener HC. Acupuncture prophylaxis of migraine no better than sham acupuncture for decreasing frequency of headaches. Evid Based Med. 2013;18:33-34.
Headache Currents 19. Molsberger A. The role of acupuncture in the treatment of migraine. CMAJ. 2012;184:391-392. 20. Witt CM, Reinhold T, Jena S, Brinkhaus B, Willich SN. Costeffectiveness of acupuncture treatment in patients with headache. Cephalalgia. 2008;28:334-345.
