Research Review By Dr. Demetry Assimakopoulos©

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Date Posted:

January 2019

Study Title:

Dose-Response and Efficacy of Spinal Manipulation for Care of Cervicogenic Headache: A Dual-Center Randomized Controlled Trial

Authors:

Haas M, Bronfort G, Evans R et al.

Author's Affiliations:

Integrative Health & Wellbeing Research Program, Earl E. Bakken Center for Spirituality & Healing, University of Minnesota, Minneapolis, MN, USA; Illumina, Inc, San Diego, CA USA; Academic Affairs, University of Western States, Portland, OR USA; The Mountain-Whisper-Light Statistics, Seattle, WA, USA.

Publication Information:

The Spine Journal 2018; 18: 1741-1754. doi: 10.1016/j.spinee.2018.02.019.

Background Information:

Cervicogenic headaches (CGH) are defined as secondary headaches emanating from a cervical/neck disorder. CGH’s have a point prevalence ranging from 0.4-4.6% and have been identified in approximately 18% of chronic headache sufferers (1-3). Spinal manipulation (SMT) is the most commonly-utilized conservative treatment by CGH sufferers; however, in spite of its common utilization, there is unfortunately no consensus on the appropriate dose of SMT to achieve maximum clinical benefit for patients. The authors of this study performed the first full-scale dose-response trial for the purpose of identifying optimal care of CGH with SMT. Their hypotheses were:
  1. There is a linear relationship between the number of SMT visits and clinical outcomes and;
  2. That a selected dose of SMT is superior to a hands-on control.

Pertinent Results:

Participants:
At baseline, the participants reported a mean of 15.6 days/month with CGH and 18.3 days/month with neck pain. The average duration of their CGH problem was 7.3 years. The mean age of participants was 41 years. There were no differing baseline characteristics between groups.

Results:
  • A reduction in CGH days was observed in all groups by the end of the study and was sustained at the 1-year post-treatment follow-up.
  • CGH days were reduced by approximately 30% for the control group, and by about 50% for the 18 SMT treatment group (that equated to 8 fewer days per month with headache!).
  • Six SMT visits had a similar outcome to the no-SMT control, while 12 SMT visits demonstrated some advantage over the control group that was not statistically significant.
  • A linear dose-response was observed for all follow-up time points, demonstrating a reduction of approximately 1 CGH day (in the prior 4-weeks) for each additional 6 visits by participants allocated to the SMT group (p = 0.05).
  • The slopes were -1.1 (p = .002) and – 1.0 (p = .010) CGH days per 6 SMT visits at the 12- and 24-week primary endpoints, respectively.
  • The greatest benefit of SMT compared with the minimal-massage control was found for 18 SMT visits at all time points (p < .05).
  • The adjusted mean difference in headache days comparing 18 SMT visits with the control were -3.3 CGH days (p = .005) and -2.9 CGH days (p = .017) over the previous 4 weeks for the 12- and 24-week primary endpoints, and -2.8 CGH days (p = .005) over all follow-up times in the longitudinal analysis. The results were similar across data-collection sites.
  • Over half of the participants appreciated a 30% reduction in CGH days by the 24-week post-intervention period. Less than half of participants reported a 50% reduction in CGH days, with the exception of the highest SMT dose group. Interestingly, an additional 5-11% of participants became positive SMT responders for every additional 6 SMT visits, meaning they were unresponsive at first, before they later became responsive.
Risk Difference and Number Needed to Treat:
  • Substantial risk differences favouring SMT over the control were mostly found after 18 SMT visits, demonstrating 0.35 (p < .001) at 12 weeks and 0.27 (p =.001) at 24 weeks for a minimal clinically important 30% improvement. These correspond to a clinically meaningful number needed to treat of 3 and 4 (Writer’s note: The average number of patients who need to be treated to reach this clinically meaningful outcome was 3 (at week 12) and 4 (at week 24), which is low, particularly in comparison to some pharmaceuticals on the market that are commonly prescribed for pain and headache management!).
  • The risk of difference for the 50% improvement threshold was 0.26 (p=.004) at 12 weeks and 0.15 (p=.088) at 24 weeks, corresponding to a number needed to treat of 4 and 7, respectively (Writer’s note: this implies that the average number of patients needed to be treated to reach a 50% difference in CGH days is 4 over 12-weeks, and 7 at 24-weeks, which was higher than the NNT required for a 30% improvement.)
Pain Intensity:
  • There was no difference between groups in average pain intensity throughout. However, all three SMT groups (that is, regardless of dose) demonstrated greater improvements than the control group in CGH-related disability.
  • The two higher SMT dose groups had a clinically important and statistically significant advantage over the control group in perceived pain change (recall). The magnitude of perceived change was considerably greater than the change computed from the average pain intensity in headache diaries. Perceived global improvement followed the same pattern as perceived pain change.
  • All SMT groups were superior to the control for confidence care is working, satisfaction with care and the disposition to seek the same therapy in the future (Writer’s note: This implies that the perception of improvement was greater than the mathematically calculated average change in pain intensity from headache diaries. This is an interesting finding, given the current dedication of research to ‘non-specific treatment effects (NSTE)’. These non-specific treatment effects imply that a specific proportion of analgesic effects are not directly related to treatments themselves, but to other seemingly irrelevant factors such as their doctor’s compassion, attentiveness, the sound of the cavitation [as opposed to the procedure itself], satisfaction with care, etc. Non-specific analgesic effects are very real and are produced via complex neurophysiological systems. This notion was not explored in the discussion of this article. Could NSTE have mediated part of the perceived positive response endorsed by the patients in the SMT groups?).
  • The pattern of improvement in group comparisons for days with neck pain and neck pain intensity were similar to the results for CGH.
Medication Use:
  • Medication use was fairly consistent across groups, and was unaffected by SMT relative to control.
Adverse Events:
There were no treatment-related severe or serious adverse events. A total of 10 adverse events occurred during the treatment phase, which were unrelated or unlikely related to the study intervention. Two cases (one of week-long headache and one of muscle tension that led to couch rest or loss of social activity) were reported, but were attributed to be part of the natural history of CGH. The remaining adverse events were secondary to unrelated conditions (ex. accidents or visceral disease). Mild-to-moderate adverse events related to treatment (ex. neck soreness, pain or stiffness, transient upper extremity pain/tingling, increased headache intensity, nausea, dizziness) were reported by approximately 40% of participants receiving SMT and approximately 20% of participants in the light massage control group. The number of mild-to-moderate adverse events was approximately 3x higher in the SMT groups compared with the control treatments but were entirely short-term and transient in nature.

Clinical Application & Conclusions:

This study was a full-scale dose-response trial for the purpose of identifying the optimal dosage of care for CGH with SMT. The results suggest that 18 visits to a chiropractor for SMT was the optimal dose for CGH relief compared to control. The responder analysis supported the advantage for 18 visits, particularly at the 12- and 24-week primary end points, where the average number of patients needed to treat to have a 30% improvement was 3 and 4 patients, respectively. The results also suggest that approximately 2/3 of patients receiving 18 SMT treatments can expect minimal clinically important improvement in headaches, and that over half can expect to achieve at least 50% improvement in CGH days. There was no significant plateau in dose-response curves over the range of SMT visits. Most secondary outcomes evaluating CGH, disability, perceived pain change, global improvement, confidence in care, satisfaction and willingness to seek the same treatment were supportive of the primary outcome findings showing a statistically significant dose-response gradient at most time points. There was however, some saturation effect beginning at 12 SMT visits for some secondary variables. Interestingly, neck pain intensity did not demonstrate meaningful improvement compared to control, which is in contrast to findings from previous systematic reviews (4, 5). The authors suggest patients may have had trouble distinguishing neck pain from their headaches.

Overall, this study demonstrated that a linear dose-response relationship between SMT visits and days with CGH that was durable to 52 weeks after the start of care. The highest and most effective dose of SMT was 18 visits.

This study confirms that SMT has a measurable and significant effect on CGH pain and frequency. It also arms clinicians with information about how many treatments may be required to impart the maximum therapeutic effect (something we can discuss with our patients). The observation that an additional 5-11% of participants became positive SMT responders for every additional 6 SMT visits was also incredibly interesting. In light of this, a longer trial of care for some CGH patients may be justified. The apparent lack of moderate-to-severe side effects also reassures clinicians and patients that SMT is a safe treatment for CGH sufferers.

Study Methods:

These authors performed a two-site, prospective, open-label RCT. 256 participants with chronic CGH were randomized to one of four dose levels of SMT (this approach was piloted in a prior, smaller study) (6, 7). All patients were scheduled for 18 chiropractic visits over 6 weeks, and were randomly assigned to receive 0, 6, 12 or 18 SMT treatments (i.e. 0-3/week) during these appointments. They received a brief, light massage at all remaining visits as a control. Follow-ups were performed via headache diary and mailed questionnaires at weeks 6, 12, 24, 39 and 52. A web-based program generated a rank-minimization scheme by balancing seven participant characteristics, including CGH days, CGH pain intensity, gender, age, differential confidence in success of SMT and massage control, previous SMT or massage care for CGH, and tension-type headache. Treatment-group assignment was concealed from participants and all personnel before allocation.

Initial screening was conducted via telephone interview, followed by eligibility assessment at two baseline visits, which took place approximately 4-weeks apart. The authors included patients who fulfilled the International Headache Society definition of CGH, which stipulates a history of at least 3 months, at least 5 headaches over 4 weeks prior to the start of care, an average of 3/10 on the pain scale and a clear temporal sequence linking the source of headache to the neck. Indications for SMT were cervical joint tenderness or restricted joint motion (joint or end play). Patients had to be 18 years of age or older and English literate.

The intervention period was 6 weeks. Treatment visits lasted 10 minutes. During these sessions, the first 5 minutes were dedicated to conducting a brief history and recording any adverse events. A hot pack was also applied to relax spinal musculature. The latter 5 minutes included a brief examination, and SMT for the experimental group(s) or light-massage for control treatments. Provider enthusiasm and treatment protocol were standardized across groups to minimize intervention bias and the potential impact of contextual factors. Analgesic medications were permitted during this trial, but all other care for CGH was discouraged in the absence of intolerable symptoms (note, there were no restrictions on care following completion of the 6 weeks of study care). High-velocity, low-amplitude (HVLA) SMT was administered to the cervical and upper thoracic regions. The specific site(s) of treatment was determined by ROM and palpatory findings from the occiput to T3 (essentially, a pragmatic chiropractic examination any of us would do with our patients). SMT was conducted at all sites of palpatory joint restriction or pain, and not in their absence (that is, the treating clinicians adjusted what they found – again, much like what most do in clinical practice). Low-velocity, low-amplitude mobilization was permitted for older adults and in cases of acute exacerbation. The light massage control treatments consisted of gentle effleurage and kneading of the neck and/or shoulder muscles. Treatment was focused to the areas of dysfunction or pain. It is noteworthy that the light massage intervention was not a true sham treatment, but rather a comparative, minimalist therapy. A sample size of 64 participants/group was pre-determined, providing the ability to detect a linear effect (slope) of 1.

Outcome Measures:

The primary outcome was CGH frequency, defined as the number of days with CGH in the 4-weeks prior to the initiation of treatment, and at 12- and 24-week follow-up. Responder analysis was conducted for the primary outcome. Potential improvement in the number of CGH days was dichotomized, using a 30% minimally clinically important change, and 50% improvement, which is a common measure of important improvement for headache research. Electronic diaries were delivered to participants using SMS or email response. Paper diaries were made available if patients were uncomfortable with electronic platforms, or if electronic platforms were unavailable. CGH frequency evaluated at 6, 39 and 52-weeks was prespecified as a secondary outcome (the baseline value was used as a covariate for the analysis).

The chief secondary outcome was average CGH pain intensity on a 0-10 scale. Additional secondary outcomes included:
  • The number of days taking medication and days with headaches other than CGH over 4-weeks, which were computed from the diaries.
  • Baseline and follow-up questionnaires, including The Headache Impact Test (HIT-6) for headache disability, quality of life using the 0-100-point visual analog scale from the Euro-QOL-5D, days with neck pain and neck pain intensity.
  • Global improvement was evaluated on a 9-point ordinal scale ranging from symptom free to as bad as it could be.

Study Strengths / Weaknesses:

Strengths:
  • This is the first larger-scale study (to our knowledge) that attempted to calculate a specific dose-response for SMT treatment of CGH.
  • The authors allowed the treating chiropractors to treat areas of pain and dysfunction based on their assessment (i.e. pragmatic treatment application).
  • The study design also included long-term follow-ups which demonstrated treatment stability after treatment was discontinued.
  • The authors utilized multiple statistical measures to demonstrate the veracity of their results.
Weaknesses:
  • The authors unfortunately did not include a true placebo group who were provided a sham treatment or no treatment at all.
  • There was also a discrepancy between the patient-reported change in CGH pain intensity, compared to what was mathematically calculated from headache pain diaries. The researchers did not explore this discrepancy, but its existence argues that pain perception is an important construct to consider in this type of research (discussed in more detail above).
  • Chiropractic treatments typically include multiple active and passive therapeutic modalities. Multimodal care was not reflected in the study, which makes the conclusions for the dose response potentially not applicable to multimodal clinical care (which, in theory at least, might be better?).

Additional References:

  1. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, 2nd edition. Cephalalgia 2004; 24(Suppl. 1):9–160.
  2. Headache Classification Committee of the International Headache Society (IHS). The International classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013; 33: 629–808.
  3. Haas M, Groupp E, Aickin M, et al. Dose-response for chiropractic care of chronic cervicogenic headache and associated neck pain: a randomized pilot study. J Manipulative Physiol Ther 2004; 27: 547– 53.
  4. Gross A, Langevin P, Burnie SJ, et al. Manipulation and mobilisation for neck pain contrasted against an inactive control or another active treatment. Cochrane Database Syst Rev 2015; (9): CD004249.
  5. Wong JJ, Shearer HM, Mior S, et al. Are manual therapies, passive physical modalities, or acupuncture effective for the management of patients with whiplash-associated disorders or neck pain and associated disorders? An update of the bone and joint decade task force on neck pain and its associated disorders by the optima collaboration. Spine J 2016; 16: 1598–630.
  6. Haas M, Spegman A, Peterson DH, Aickin M,Vavrek D. Dose-response and efficacy of spinal manipulation for chronic cervicogenic headache: a pilot randomized controlled trial. Spine J 2010; 10: 117–28.
  7. Haas M, Vavrek D, Peterson D, Polissar NL, Neradilek MB. Dose- response and efficacy of spinal manipulation for care of chronic low back pain: a randomized controlled trial. Spine J 2014; 14: 1106–16.