Treatment Of Episodic Tension-type Headache Research Articles

Quality appraisal of existing guidelines for the management of headache disorders by the AGREE II's method.

To evaluate the quality of existing clinical practice guidelines for headache management and their main recommendations. Evidence-based clinical practice guidelines have been developed to support the clinical decision-making. However, to achieve this goal, the quality of these guidelines must be ensured. A systematic search for clinical practice guidelines for headache management was conducted in the PubMed database, in websites of known guideline developers and in websites of known headache associations. The quality appraisal was performed through the Appraisal of Guidelines for Research and Evaluation II method. Twelve guidelines were evaluated. The domains of rigor of development, applicability, and editorial independence, which most influence the overall quality of guidelines, had the lowest average scores and the highest standard deviation rates (61% ± 23; 37% ± 20; 53% ± 31). The main recommendations regarding medication use for acute treatment of episodic tension-type headache and migraine in adult patients consisted of paracetamol, acetylsalicylic acid, and other nonsteroidal anti-inflammatory drugs in all guidelines. The statistical results indicate that the appraised guidelines have room for both individual and collective improvement. In addition, there is a well-established medication recommendation pattern among all guidelines evaluated.

Aspirin for acute treatment of episodic tension-type headache in adults.

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headache days per month), and chronic TTH (15 headache days per month or more). Aspirin is one of a number of analgesics suggested for acute treatment of episodic TTH. To assess the efficacy and safety of aspirin for acute treatment of episodic tension-type headache (TTH) in adults compared with placebo or any active comparator. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database from inception to September 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral aspirin for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. For various outcomes (predominantly those recommended by the International Headache Society (IHS)), we calculated the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT), one additional harmful outcome (NNH), or to prevent one event (NNTp) for oral aspirin compared to placebo or an active intervention.We assessed the evidence using GRADE and created a 'Summary of findings' table. We included five studies enrolling adults with frequent episodic TTH; 1812 participants took medication, of which 767 were included in comparisons of aspirin 1000 mg with placebo, and 405 in comparisons of aspirin 500 mg or 650 mg with placebo. Not all of these participants provided data for outcomes of interest in this review. Four studies specified using IHS diagnostic criteria; one predated commonly recognised criteria, but described comparable characteristics and excluded migraine. All participants treated headaches of at least moderate pain intensity.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged one study to be at high risk of bias due to small size.There were no data for aspirin at any dose for the IHS preferred outcome of being pain free at two hours, or for being pain free at any other time, and only one study provided data equivalent to having no or mild pain at two hours (very low quality evidence). Use of rescue medication was lower with aspirin 1000 mg than with placebo (2 studies, 397 participants); 14% of participants used rescue medication with aspirin 1000 mg compared with 31% with placebo (NNTp 6.0, 95% confidence interval (CI) 4.1 to 12) (low quality evidence). Two studies (397 participants) reported a Patient Global Evaluation at the end of the study; we combined the top two categories for both studies to determine the number of participants who were 'satisfied' with treatment. Aspirin 1000 mg produced more satisfied participants (55%) than did placebo (37%) (NNT 5.7, 95% CI 3.7 to 12) (very low quality evidence).Adverse events were not different between aspirin 1000 mg and placebo (RR 1.1, 95% CI 0.8 to 1.5), or aspirin 500 mg or 650 mg and placebo (RR 1.3, 95% CI 0.8 to 2.0) (low quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing aspirin doses between 500 mg and 1000 mg with placebo was low or very low. Evidence was downgraded because of the small number of studies and events, and because the most important measures of efficacy were not reported.There were insufficient data to compare aspirin with any active comparator (paracetamol alone, paracetamol plus codeine, peppermint oil, or metamizole) at any of the doses tested. A single dose of aspirin between 500 mg and 1000 mg provided some benefit in terms of less frequent use of rescue medication and more participants satisfied with treatment compared with placebo in adults with frequent episodic TTH who have an acute headache of moderate or severe intensity. There was no difference between a single dose of aspirin and placebo for the number of people experiencing adverse events. The amount and quality of the evidence was very limited and should be interpreted with caution.

Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults.

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size.For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain-free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence).Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events. Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.

Ibuprofen for acute treatment of episodic tension-type headache in adults.

Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites. We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS). We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.For the IHS-preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high-quality evidence). No serious adverse events were reported. Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension-type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.

A Comparison of Efficacy and Safety of Non-steroidal Anti-inflammatory Drugs versus Acetaminophen in the Treatment of Episodic Tension-type Headache: A Meta-analysis of Randomized Placebo-controlled Trial Studies

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used in the treatment of tension headache. The objective of this study was to evaluate and compare the efficacy and safety of single doses of acetaminophen and NSAIDs using meta-analysis of randomized placebo-controlled trial studies.MethodsWe searched MEDLINE, EMBASE, CINAHL, Cochrane, KMbase, KoreaMed, RiCH, National Assembly Library, Riss4u, and DBPIA for studies released through 27th July 2010. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. Review Manager 5.0 was used for statistics.ResultsWe identified 6 studies. The relative benefit of the NSAIDs group compared to the acetaminophen group for participants with at least 50% pain relief was 1.18 (95% confidence interval [CI], 0.99 to 1.39; I2 = 85%). We did subgroup analysis based on allocation concealment versus non-allocation concealment, and low-dose NSAIDs versus high-dose NSAIDs. The relative benefit of the low-dose NSAIDs subgroup to the acetaminophen group was 0.98 (95% CI, 0.91 to 1.06; I2 = 0%). However, the heterogeneity of other subgroup analysis was not settled. The relative risk for using rescue medication of the NSAIDs group compared to the acetaminophen group was 0.84 (95% CI, 0.64 to 1.12; I2 = 47%). The relative risk for adverse events was 1.31(95% CI, 0.96 to 1.80; I2 = 0%).ConclusionIn this meta-analysis, there was no difference between low-dose NSAIDs and acetaminophen in the efficacy of the treatment for tension type headache. The results suggested that high-dose NSAIDs have more effect but also have more adverse events. The balance of benefit and harm needs to be considered when using high-dose NSAIDs for tension headache.

Comments on Statistical Issues in November 2012

In this section, we explain the statistical models and evaluation of heterogeneity among in meta-analysis, which appeared in the articles titled, A comparison of efficacy and safety of nonsteroidal anti-inflammatory drugs versus acetaminophen in the treatment of episodic tension-type headache: a meta-analysis of randomized placebo-controlled trial studies by Yoon et al.1) and Use of proton pump inhibitor and risk of colorectal cancer: a meta-analysis of observational studies by Ahn et al.2), both published in September 2012.

Indomethacin/Prochlorperazine/Caffeine

The indomethacin/prochlorperazine/caffeine fixed combination (Difmetré®) combines the NSAID indomethacin with the phenothiazine antiemetic prochlorperazine and caffeine. It is currently available as two oral (effervescent tablet and coated tablet) and two rectal (suppository and low-dose suppository) formulations. Oral and rectal formulations of indomethacin/prochlorperazine/caffeine were effective and generally well tolerated in the treatment of migraine and episodic tension-type headache (TTH) in adult patients participating in randomized, multicentre, active-comparator controlled studies. For the most part, the efficacy of oral indomethacin/prochlorperazine/caffeine did not significantly differ from that of oral sumatriptan in patients with migraine and oral nimesulide in patients with episodic TTH. With rectal administration, indomethacin/prochlorperazine/caffeine was, in general, significantly more effective than sumatriptan in patients with migraine. Thus, oral and rectal formulations of indomethacin/prochlorperazine/caffeine provide a further option in the acute treatment of migraine and in the treatment of episodic TTH in adult patients.

Novelty in the treatment of episodic tension-type headache

Frequent episodic tension-type headache (ETTH) is a serious medical problem that is primarily due to its high prevalence. Nonsteroidal anti-inflammatory drugs (NSAIDs) whose efficiency is determined by the rapid and complete regression of cephalgia are primarily used to relieve an ETTH attack. One of the ways to enhance the effect of NSAIDs is their combination with agents that accelerate their absorption or potentiate their action, with caffeine in particular; however, the use of combination agents is limited by a risk for drug-induced headache. A step on the road to the design of effective and safe analgesics has been the development of the combination drug Novigan that contains ibuprofen (400 mg) and the spasmolytics pitofenone (5 mg) and fenpiverinium (0.1 mg). Objective: to study the efficacy of Novigan versus ibuprofen 400 mg in relieving an ETTH attack. Subjects and methods. Fifty patients (mean age 37.1±10.9 years) with frequent ETTH that met the criteria of the International Classification of Headache Disorders, 2nd Edition, were examined. For relief of ETTH attacks, 30 patients used Novigan and 20 took ibuprofen in a dose of 400 mg. Results. There was a significant reduction in the intensity of cephalgia 49.9±35.8 and 68.2±45.9 min after drug administration in the Novigan and ibuprofen 400 mg groups, respectively (p = 0.007). The proportion of respondents was higher in the Novigan group (73.3%) than that in the ibuprofen 400 mg group (60%), which is close to the statistically significant difference (p = 0.085). The efficacy predictors were less pain intensity (p < 0.001) and a shorter time after onset (p < 0.001) in the ibuprofen 400 mg group at administration of the drug and only less pain intensity in the Novigan group at that moment (p = 0.07). Conclusion. Novigan is a combination analgesic that rapidly and effectively relieves an ETTH attack, including that of high intensity, as well as extended ETTH attack.

Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension‐type headache: a double‐blind, randomized, nimesulide‐controlled, parallel group, multicentre trial

In this double-blind, randomized, parallel group, multicentre study the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) and nimesulide were compared over an 8-h period in the treatment of two consecutive episodes of tension-type headache (TTH). Both drugs were administered orally. Of 54 randomized patients, 40 were compliant to the protocol. More patients on IndoProCaf than on nimesulide were pain-free at 2 h post-dose (45% vs. 10%; P<0.05), reached a pain reduction of at least 50% at 2 (75% vs. 30%; P<0.05) and 4 h post-dose (90% vs. 58%; P<0.05), and had a statistically significant lower mean time to a 50 and 100% pain reduction in the second TTH episode. A higher percentage of patients reached a 50 or 100% pain reduction at 2 h post-dose with IndoProCaf compared with nimesulide, in two of two treated TTH episodes. A clinically and statistically significant change within each treatment group over time was found for the severity of pain, the headache intensity difference (HID), the sum of headache intensity difference (SHID), the maximum headache intensity difference (MAXHID), the headache relief (HER), the sum of total headache relief (TOTHER) and the maximum headache relief (MAXHER). In conclusion, IndoProCaf showed to be superior, but globally not statistically different from nimesulide in the treatment of episodic TTH. Both drugs were very effective and well tolerated.

Lumiracoxib Is Effective in the Treatment of Episodic Tension‐Type Headache

To evaluate the efficacy of single doses of lumiracoxib, the most selective cyclo-oxygenase (COX)-2 inhibitor, in the treatment of episodic tension-type headache (ETTH), with particular emphasis on time to onset of analgesia. ETTH is the most frequently occurring type of headache with an annual prevalence rate of up to 40%. Some patients with ETTH do not respond to currently available therapies, thus an effective analgesic is needed that provides a rapid onset of analgesia alongside significant pain relief. Lumiracoxib is the most selective COX-2 inhibitor developed for the treatment of acute and chronic pain. In this single-center, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study, patients with ETTH were randomly assigned to receive single-dose lumiracoxib (200 or 400 mg, n = 60 in each group) or placebo (n = 30) within 1 hour of an ETTH. Efficacy was assessed over a 3-hour period, the primary efficacy variable being the time to onset of analgesia. Other efficacy variables included summed pain intensity difference from 0 to 3 hours after dosing, time-specific pain intensity difference, time-specific pain relief, time-specific pain relief intensity difference, total pain relief over 0 to 3 hours, patient's global evaluation of treatment effect, the proportion of patients who achieved onset of analgesia by 1 hour and time to rescue medication intake. Safety was assessed by monitoring and recording of all adverse events (AEs). The median time to onset of analgesia was significantly faster for lumiracoxib 200 mg (47 minutes; 95% confidence interval [CI]: 41, 52) and lumiracoxib 400 mg (41 minutes; 95% CI: 36, 48) than for placebo (>3 hours; both P < .001). Both doses of lumiracoxib were significantly superior to placebo for all secondary efficacy variables. There were no AEs recorded in any treatment group. Single 200 or 400 mg doses of lumiracoxib provided rapid and effective relief from the acute pain associated with ETTH.

Novel therapeutic agents: Lumiracoxib, a novel COX-2 selective inhibitor, is effective in the treatment of episodic tension-type headache

A majority of the general population will experience an episodic tension-type headache (ETTH) during their lifetime. The objective of this double-blind, randomized, single-center, in-patient, placebo-controlled, parallel-group trial was to evaluate the analgesic efficacy of a single dose of lumiracoxib 200mg or 400mg, or placebo, in the treatment of ETTH, with emphasis on the time to onset of analgesia. A total of 150 patients with moderately severe to severe pain were randomized to receive lumiracoxib 200mg (n=60), lumiracoxib 400mg (n=60) or placebo (n=30) within 1 hour of onset of an ETTH. Pain assessments were performed at scheduled timepoints for 3 hours after dosing; the two-stopwatch technique was used to determine time to onset of analgesia, the primary efficacy parameter. For time to onset of analgesia, both doses of lumiracoxib were statistically superior to placebo (p<0.001) and comparable to each other. Median (95% CI) time to onset of analgesia was 47 (41, 52) and 41 (36, 48) minutes for lumiracoxib 200mg and 400mg, respectively (placebo >3 hours). A significantly greater proportion of subjects receiving lumiracoxib 200mg (70%) or 400mg (75%) experienced onset within 1 hour compared with those receiving placebo (30%; both p<0.001). For pain intensity difference and pain relief scores at individual timepoints (1, 2 and 3 hours), and for summed measures combining scores over 3 hours, both doses of lumiracoxib were superior to placebo (p<0.05) and generally comparable to each other. Similar results were obtained for patient global evaluation of treatment effect. No adverse events were reported. In summary, single 200mg or 400mg doses of lumiracoxib provided rapid and effective relief of pain associated with ETTH. Both lumiracoxib doses were well tolerated.

Current and potential future drug therapies for tension-type headache.

Tension-type headache is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any pharmacologic therapy. Simple analgesics and nonsteroidal anti-inflammatory drugs are the mainstays of treatment of episodic tension-type headache. The tricyclic antidepressant amitriptyline is the drug of choice in the preventive treatment of chronic tension-type headache. Progress in basic neuroscience has emphasized the importance of nitric oxide inhibition and N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid receptor antagonism in the treatment of chronic pain. It has been demonstrated that inhibition of nitric oxide is effective in chronic tension-type headache. These interesting data indicate that more specific and effective treatment possibilities will emerge in the future.

Intravenous chlorpromazine in the acute treatment of episodic tension-type headache: a randomized, placebo controlled, double-blind study

Acute headache is a very frequent symptom, responsible for a significant percentage of caseload at primary care units and emergency rooms. Chlorpromazine is easily available in such settings. The aim of this study is to conduct a randomized, placebo-controlled, double-blind study to assess the efficacy of chlorpromazine on the acute treatment of episodic tension-type headache. We randomized 30 patients to receive placebo (10 ml of saline intravenous injections) and 30 patients to receive 0.1 mg/Kg chlorpromazine intravenously. We used 7 parameters of analgesic evaluation. Patients receiving chlorpromazine showed a statistically significant improvement (p < 0.05 and p < 0.01) of pain compared to placebo, far up to 30 minutes after the drug administration. The therapeutic gain was 36.7% in 30 minutes and 56.6 % in 60 minutes. The number needed to treat (NNT, the reciprocal or the therapeutic gain) was 2.7 in 30 minutes and 1.8 in 60 minutes. There were reductions in the recurrence and in the use of rescue medication in the chlorpromazine group. We can conclude that intravenous chlorpromazine is an effective drug to relief the pain in tension-type headache.

Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial

Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial