The current review and NCG were based on the Population, Intervention, Comparison and Outcome (PICO) framework, with the methodology following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. This review adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and its protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) in 2020, ID: CRD42020220124.

Organization of the work

The Danish Knowledge Centre on Headache Disorders invited a multidisciplinary expert group with the purpose of developing a NCG for non-pharmacological treatment for patients with TTH as an aid to assist healthcare professionals and patients with TTH to identify and seek the most relevant non-pharmacological treatment strategies. The study process was led by the Danish Knowledge Centre on Headache Disorders (CVH, LNC, JMH) assisted by a specialist in literature search (KB) and a research methodologist (HEC). Members of the multidisciplinary expert group were appointed by Danish societies, i.e. the Chiropractor Association, the Osteopath Association, the Society for Physiotherapy, the Psychologist Association, the Medical Acupuncture, and the Neurological Society. Patient organizations and other representatives from the Danish health care system were included as a reference group. They provided feedback on the questions investigated, patient preferences, and on the final recommendations. The draft of the NCG was peer-reviewed by two external reviewers and disseminated for public feedback i.e. to relevant stakeholders.

Clinical questions

Five PICO questions were constructed in order to investigate the effect of specific non-pharmacological interventions for patients diagnosed with TTH.


Patients diagnosed with TTH according to the International Classification of Headache Disorder 2nd-3rd edition (ICHD 2–3) [13, 29] were included. The study population was aged 18 years or older. Studies of patients suffering from both TTH and migraine were also included but only if results were reported separately for TTH. We excluded studies of any other primary or secondary headache disorders. If studies of cervicogenic headache also included patients with TTH, there had to be a clear distinction between these two classifications based on ICHD 2–3 for both headache disorders and/or the classification proposed by Sjaastad et al. for cervicogenic headache [30].


The investigated interventions included: 1) manual joint mobilisation techniques 2) supervised physical activity 3) psychological treatment 4) acupuncture and 5) patient education.


1) Maunal joint mobilisation techniques compared to no manual joint mobilisation techniques, other treatment than manual joint mobilisation techniques, treatment as usual, placebo, sham intervention or waitlist; 2) Supervised physical activity compared to no supervised physical activity, other treatment than physical activity, treatment as usual, placebo, sham intervention or waitlist; 3) Psychological treatment compared to no psychological treatment, other treatment than psychological treatment, treatment as usual, placebo, sham intervention or waitlist; 4) Acupuncture compared to no acupuncture, other treatment than acupuncture, treatment as usual, placebo, sham intervention (studies that only used sham acupuncture with skin penentration as control group were excluded) or waitlist; 5) Patient education compared to no patient education, other treatment than patient education, treatment as usual, placebo, sham intervention or waitlist.


Two primary outcomes were selected for each PICO question: headache frequency in days per month and quality of life, both measured at the end of treatment. Additional primary outcomes were selected for psychological treatment (functioning) and patient education (degree of increased knowledge about illness and treament). A complete list of primary and secondary outcomes for each PICO question can be found in the Additional file 1 (Table 1).


Manual joint mobilisation techniques

Manual joint mobilisation techniques were defined as all manual techniques, mobilisation or manipulation within the normal range of motion of the joint, aimed at affecting the joints, muscles and connective tissues of the neck, chest and lower back.

Supervised physical activity

Supervised physical activity was defined as planned, repeated and structured physical activity [43].

Psychological treatment

Phychological treatment refers to approaches that address self-efficacy to decrease negative effect of reduced functioning and improve quality of life despite headache pain and headache related disability.


Acupuncture was defined as a treatment where thin needles are inserted into the body including dry-needling and trigger point acupuncture excluding electroacupuncture.

Patient education

A disease-specific education aiming at improving the understanding of the disorder and treatment options, thus improving both knowledge and skills to master the life with recurring headache. Disease specific education can be conducted individually and in classes and also address family members containing information about the disease, its treatment, medication overuse, self-care, lifestyle, physical activity, regular diet and sleep. The intervention had to be conducted by a trained professional.

Literature search and study selection

A systematic search was made on February 2020 to July 2020. Databases included EMBASE, PsycINFO, MEDLINE, CINAHL and PEDRO. The search was performed for Randomised Controlled Trials (RCT) included in existing guidelines and systematic reviews. Subsequently, an individual search for RCTs was performed, with the search date limited to the date of the latest search in identified existing systematic reviews. There was no restriction regarding publication status. The studies had to be published in English, Swedish, Norwegian or Danish. The search protocol can be found in Additional file 2.

The title and abstract of studies were independently screened by one review author followed by an assessment of full text of potential studies by two review authors. Any disagreement was recognised and resolved. The authors evaluating the studies were not blinded.

Data extraction, risk of bias and quality assessment

Systematic reviews or existing clinical guidelines were identified and the methodological quality was evaluated using the AMSTAR [44] and AGREE [45] tools, respectively. Only systematic reviews and guidelines of sufficient quality were included, followed by data extraction of individual RCTs mentioned in the review and/or clinical guideline. Data including population demographics, intervention and control details, outcome and time measurement were independently extracted, by two review authors, from relevant RCTs. Risk of bias within individual RCTs was independently assessed by two review authors using the Cochrane risk of bias tool [46]. Any discrepancy was resolved through discussion. The review authors were not blinded.

Summary measures

Meta-analysis for each outcome were performed if data, in the included RCTs, was comparable. Data was extracted in the online software program, Covidence [47] and subsequently exported to RevMan5 [48], where pooled estimates of effects were calculated using the random-effect model. Dichotomous outcomes were calculated as relative risks (RR) and continous outcomes as mean differences (MD). If different scales were used in the measurement of continuous outcomes, a standardised mean difference (SMD) was applied. A 95% confidence interval was calculated for both dichotomous and continuous outcomes. I2 statistics were used for quantification of statistical heterogeneity (I2 > 50% was considered substantial heterogeneity). There was insufficient data to allow for any subgroup analysis. Results were displayed in forest plots for each outcome.

Certainty of evidence and recommendations

The GRADE approach was applied to assess the certainty of evidence obtained for each outcome. One of four possible rating was possible; high, moderate, low or very low. If needed, downgrading the certainty of evidence was done based on the extent of risk of bias, inconsistency, indirectness, imprecision, and publication bias. The overall certainty of evidence for each clinical question was based on the lowest rating of the primary outcome.

If evidence was available for a given clinical question, either a strong or weak recommendation, for or against an intervention was made. If no evidence was available, a consensus recommendation was made. Recommendations were based on a combined evaluation of the certainty of evidence, patient preferences, and the identified benefits and harms.

Patient preferences and consensus recommendation

The Danish Knowledge Centre on Headache Disorders performed a survey on patients’ expectations concerning treatments offered by chiropractors, physiotherapists, psychologists, acupuncturists and courses about knowledge on illness and treatment. They were also asked whether they would seek this treatment again. The headache population was recruited by a modified snowball sampling via facebook and patient organizations.

Patient preferences and consensus recommendation were based on direct patient involvement based on responses from the survey, direct feedback from chairmen (ABO, BOL) and board member (JB) representing Danish Migraine Association, Denmark’s Patient Society for People with Headache, and the Migraine and Headache Society, respectively. Additionally, patient preferences were based on expert opinion of the multidisciplinary working group formed by their experience in working with patients in daily practice.

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