OBJECTIVE: To compare the effectiveness of spinal manipulation and pharmaceutical treatment (amitriptyline) for chronic tension-type headache. DESIGN: Randomized controlled trial using two parallel groups. The study consisted of a 2-wk baseline period, a 6-wk treatment period and a 4-wk posttreatment, follow-up period. SETTING: Chiropractic college outpatient clinic. PATIENTS: One hundred and fifty patients between the ages of 18 and 70 with a diagnosis of tension-type headaches of at least 3 months' duration at a frequency of at least once per wk. INTERVENTIONS: 6 wk of spinal manipulativetherapy provided by chiropractors or 6 wk of amitriptyline treatment managed by a medical physician. MAIN OUTCOME MEASURES: Change in patient-reported daily headache intensity, weekly headache frequency, over-the-counter medication usage and functional health status (SF-36). RESULTS: A total of 448 people responded to the recruitment advertisements; 298 were excluded during the screening process. Of the 150 patients who were enrolled in the study, 24 (16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%) from the amitriptyline therapy group. During the treatment period, both groups improved at very similar rates in all primary outcomes. In relation to baseline values at 4 wk after cessation of treatment, the spinal manipulation group showed a reduction of 32% in headache intensity, 42% in headache frequency, 30% in over-the-counter medication usage and an improvement of 16% in functional health status. By comparison, the amitriptyline therapy group showed no improvement or a slight worsening from baseline values in the same four major outcome measures. Controlling for baseline differences, all group differences at 4 wk after cessation of therapy were considered to be clinically important and were statistically significant. Of the patients who finished the study, 46 (82.1%) in the amitriptyline therapy group reported side effects that included drowsiness, dry mouth and weight gain. Three patients (4.3%) in the spinal manipulation group reported neck soreness and stiffness. CONCLUSIONS: The results of this study show that spinal manipulative therapy is an effective treatment for tension headaches. Amitriptyline therapy was slightly more effective in reducing pain at the end of the treatment period but was associated with more side effects. Four weeks after the cessation of treatment, however, the patients who received spinal manipulative therapy experienced a sustained therapeutic benefit in all major outcomes in contrast to the patients that received amitriptyline therapy, who reverted to baseline values. The sustained therapeutic benefit associated with spinal manipulation seemed to result in a decreased need for over-the-counter medication. There is a need to assess the effectiveness of spinal manipulative therapy beyond four weeks and to compare spinal manipulative therapy to an appropriate placebo such as sham manipulation in future clinical trials.

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CTTH における指圧療法あるいは amitriptyline を用いた薬理学療法の予防法の有効性を検証すること．

Chiropractic college outpatient clinic

6 週間の指圧療法あるいは amitriptyline を用いた薬物療法を平行して２群で行った．

主要評価項目とそれに用いた統計学的手法

治療期間中には両群ともに同様な頭痛改善率を示したが，治療終了 4 週後の時点では，指圧治療群では，治療開始前に比べ頭痛強度は 32%, 頭痛頻度は 42%, 鎮痛剤の服用回数は 30%, 健康状態も 16% 改善したが，薬物治療群では有意な改善は得られなかった．薬物治療群では眠気，口腔内乾燥，体重増加など 82.1% の副作用を，指圧群では，頸部痛や硬直感を 4.3% に認めた．

指圧療法は， CTTH の予防法として有効である． Amitriptyline 治療は，治療終了時では指圧療法に比し頭痛回数という点ではより有効であったが，より多くの副作用が認められた．しかし，治療終了後４週間後の時点では，指圧治療群の方がより持続した治療効果を得られた .

Publication Types:
* Clinical Trial
* Randomized Controlled Trial

MeSH Terms:
* Adult
* Aged
* Amitriptyline/therapeutic use*
* Chiropractic/methods*
* Comparative Study
* Drugs, Non-Prescription/therapeutic use
* Female
* Follow-Up Studies
* Humans
* Male
* Middle Aged
* Pain Measurement
* Research Support, Non-U.S. Gov't
* Tension Headache/drug therapy
* Tension Headache/therapy*

Substances:
* Drugs, Non-Prescription
* Amitriptyline

The primary aim of this study was to investigate which treatment, patient, and study characteristics are related to treatment outcome in tension headache. Literature on the subject was obtained by searching for articles published in English through CD-rom Compact Cambridge and PSYCHLIT (1970/1993) on the subjects of headache and tension or muscle contraction in combination with therapy or treatment. Inclusion criteria were prospective design, tension headache, > or = five subjects per condition; pre- and posttreatment scores available, subjects older than 16 years. Each article was independently reviewed and its data encoded by the two authors. Finally, 78 articles with 175 treated and nontreated conditions (total of 2,866 patients) were selected for this study. Meta-analysis revealed that cognitive therapy, relaxation, or electromyelographic (EMG) biofeedback alone or in combination with relaxation were superior to no treatment and to pseudo/placebo therapy. Pharmacological and other therapies were better than no treatment. However, restricting the analyses to studies using a headache diary, the results of pharmacological therapy were comparable to those of placebo therapy. Moreover, a better treatment outcome was found in studies with a relatively short duration of headache complaints (r -0.31) and with a relatively younger patient sample (r = -0.22). The year of publication was negatively related with improvement (r = -0.36). No relationship between treatment outcome and other treatment characteristics (duration, transfer of treatment), patient characteristics (gender, method of patient recruitment), and study characteristics (internal validity of the study, criteria for diagnosing tension headache, number of patients, drop-outs) was found. These findings suggest that treatment outcome may be affected more by patient characteristics than by treatment characteristics. Finally, some practical and research implications of these findings are discussed.

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再発性緊張型頭痛の治療：メタ解析

どのような治療法，患者，研究デザインが最も緊張型頭痛の予後に関連しているかを明らかにすること．

1970 年から 1993 年にかけて CD-rom Compact Cambridge and PSYCHLIT に掲載された英語で書かれた論文検索で， headache と tension あるいは muscle contraction を therapy あるいは treatment を組み合わせてで検索した． Inclusion 基準として，前向き研究，緊張型頭痛， 5 人以上の対象患者であること，治療前後のスコアーが記載されていること，患者は 16 歳以上であることなどである．２人の reviewers によって選出された．

主要評価項目とそれに用いた統計学的手法

最終的に 78 編の論文が選出された． ( 合計 2,866 人の患者 ) ．メタ解析の結果，認知治療，緩和治療，筋電図生体フィードバック療法のみ，あるいは緩和療法との併用療法が未治療群やプラセボ治療群より勝っていた．薬物治療あるいはその他の治療は，未治療より勝っていなかった．しかし，頭痛日記を用いている試験結果に絞ると，薬物治療成績は，プラセボ効果と同等であり，更に，頭痛持続期間が短い場合や若年者では薬物療法の治療成績が勝っていた．論文掲載年度と治療成績には逆相関がみられた．治療成績と，治療要因（治療の持続期間，治療法），患者要因，試験の信頼度（患者の性，患者の登録法），試験方法（緊張型頭痛の診断基準，患者数，脱落率）には有意な関係がなかった．

治療予後は，治療法自体より患者の特徴によって影響を受ける可能性がある．

Publication Types:
* Meta-Analysis

MeSH Terms:
* Humans
* Recurrence
* Tension Headache/drug therapy
* Tension Headache/psychology
* Tension Headache/therapy*

In a controlled trial the effect of traditional Chinese acupuncture v. placebo acupuncture was evaluated in 18 patients with chronic tension headache (mean disease duration 15 years). All patients suffered from daily or frequently recurring headache, the intensity of which was recorded by the patient over a period of 15 weeks. Each patient was treated by traditional Chinese acupuncture as well as by placebo acupuncture in a cross-over design following randomization. Each period of treatment comprised six treatments. Traditional Chinese acupuncture was found to be significantly more pain-relieving than placebo acupuncture, according to the pain registration of the patients themselves. The pain reduction was 31%. Acupuncture is therefore found to be a reasonable treatment for chronic tension headache.

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伝統的中国式の鍼灸治療とプラセボ鍼灸治療をそれぞれ３週間ずつ行い，有効性について評価した．

主要評価項目とそれに用いた統計学的手法

伝統的中国式の鍼灸治療群はプラセボ群に比べ有意に改善した．

伝統的中国式の鍼灸治療群は有効な治療法である．

Publication Types:
* Clinical Trial
* Randomized Controlled Trial

MeSH Terms:
* Acupuncture Therapy*
* Chronic Disease
* Clinical Trials
* Headache/therapy*
* Humans

The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.

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CTTH （ 48 人）と ETTH （ 34 人）の合計 82 人である．

治療開始前 4 週間， 12 週間の治療期間，治療終了後の 4 週間１ヶ月毎に評価し，有効性について検討した．

主要評価項目とそれに用いた統計学的手法

amitriptyline 治療は ETTH では有効ではない．

MeSH Terms:
* Adrenergic Uptake Inhibitors/therapeutic use*
* Amitriptyline/therapeutic use*
* Analgesics/therapeutic use
* Chronic Disease
* Humans
* Recurrence
* Tension Headache/classification
* Tension Headache/drug therapy*
* Tension Headache/etiology

Substances:
* Adrenergic Uptake Inhibitors
* Analgesics
* Amitriptyline

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CTTH の診断基準に合致した 60 名

主要評価項目とそれに用いた統計学的手法

客観的，主観的な改善効果， Hamilton17 によるうつの評価，鎮痛薬の使用減少と副作用を評価項目とした．

CTTH に対するミルタザピンの効果はアミトリプチリンに優る．

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ジクロフェナク -K12.5mg （ n ＝ 160 ），ジクロフェナク 25mg （ n=156 ），イブプロフェン 400mg （ n=151 ）およびプラセボ（ n=153 ）．

主要評価項目とそれに用いた統計学的手法

単回で投与されたジクロフェナク -K12.5mg および 25mg は ETH を効果的に緩和し，イブプロフェン 400mg と同等の効果が認められた．

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アセトアミノフェン 1,000mg 群
ナプロキセン 375mg 群
プラセボ群　の薬物治療

主要評価項目とそれに用いた統計学的手法

本試験により，中等度〜重症の緊張型頭痛の治療において， OTC アセトアミノフェン 1,000mg と処方薬ナプロキセン 375mg は共に有効であり，忍容性が高いことが示された．

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プラセボ群（生理食塩水 10mｌ静注）
クロロプロマジン群（ 0.1mg/kg 静注）の両薬剤投与

主要評価項目とそれに用いた統計学的手法

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二重盲検プラセボ対照薬物投与

主要評価項目とそれに用いた統計学的手法

治療薬剤は有意に 1 週間の鎮痛薬使用量を減少させた． Sertraline はアミトリプチリンが無効あるいは忍容性が低い場合の有用な代替治療である．

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脊柱手技療法（ SMT ）

主要評価項目とそれに用いた統計学的手法

SMT は頸原性頭痛に対しマッサージより効果があることが判明した．また SMT は緊張型頭痛および片頭痛に対しファーストラインとされる予防療法の処方薬と同等の効果を持つ事も判明した．

BACKGROUND: Studies in animals have shown that nitric oxide plays an important part in central sensitisation and that inhibitors of nitric oxide synthase (NOS) decrease sensitisation in models of persistent pain. The efficacy of inhibitors of NOS has not been tested in patients with tension-type chronic headache. We aimed to show whether N(G)-monomethyl-L-arginine hydrochloride (L-NMMA), an inhibitor of NOS, is effective in relieving pain in such patients. METHODS: We undertook a randomised double-blind, crossover trial of 16 patients with chronic-tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week in a randomized order. Headache intensity was measured on a 100 mm visual analogue scale, and on a verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. The primary endpoint was reduction of pain intensity on the visual analogue scale by the active treatment compared with placebo. FINDINGS: L-NMMA reduced pain intensity on the visual analogue scale significantly more than placebo: 120 min after start of treatment, the mean pain score was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p=0.01). Pain intensity on the verbal rating scale was also significantly lower for treatment with L-NMMA than for treatment with placebo (p=0.02). INTERPRETATION: Inhibition of NOS had an analgesic effect in chronic tension-type headache. Further tests are required before clinical application.

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主要評価項目とそれに用いた統計学的手法

NOS inhibitor である L-NMMA は慢性型緊張型頭痛に有効である．

Publication Types:
* Clinical Trial
* Randomized Controlled Trial

MeSH Terms:
* Adult
* Double-Blind Method
* Enzyme Inhibitors/therapeutic use*
* Female
* Humans
* Male
* Middle Aged
* Nitric-Oxide Synthase/antagonists & inhibitors*
* Pain Measurement
* Research Support, Non-U.S. Gov't
* Tension Headache/drug therapy*
* omega-N-Methylarginine/therapeutic use*

Substances:
* Enzyme Inhibitors
* omega-N-Methylarginine
* Nitric-Oxide Synthase

CONTEXT: Episodic tension-type headache is common and is often treated using manual therapies. Few data exist for the efficacy of these interventions. OBJECTIVE: To determine the effects of spinal manipulation therapy on adults with episodic tension-type headache. DESIGN: Randomized controlled trial lasting 19 weeks. SETTING: Outpatient facility of a National Health Service-funded chiropractic research institution in Denmark . PARTICIPANTS: Volunteer sample of 26 men and 49 women aged 20 to 59 years who met the diagnostic criteria for episodic tension-type headache as defined by the International Headache Society. INTERVENTION: Participants were randomized into 2 groups, 1 receiving soft tissue therapy and spinal manipulation (the manipulation group), and the other receiving soft tissue therapy and a placebo laser treatment (the control group). All participants received 8 treatments over 4 weeks; all treatments were performed by the same chiropractor. MAIN OUTCOME MEASURES: Daily hours of headache, pain intensity per episode, and daily analgesic use, as recorded in diaries. RESULTS: Based on intent-to-treat analysis, no significant differences between the manipulation and control groups were observed in any of the 3 outcome measures. However, by week 7, each group experienced significant reductions in mean daily headache hours (manipulation group, reduction from 2.8 to 1.5 hours; control group, reduction from 3.4 to 1.9 hours) and mean number of analgesics per day (manipulation group, reduction from 0.66 to 0.38; control group, reduction from 0.82 to 0.59). These changes were maintained through the observation period. Headache pain intensity was unchanged for the duration of the trial. CONCLUSION: As an isolated intervention, spinal manipulation does not seem to have a positive effect on episodic tension-type headache.

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指圧師によるマッサージと上部頚髄指圧を受ける指圧治療群とマッサージと低出力レザー光線照射をうける対照群の 2 群にわけて検討した． 4 週間にわたり合計 8 回の治療を行い，治療前後で 19 週にわたる臨床試験である．

主要評価項目とそれに用いた統計学的手法

指圧自体に，単独治療として ETTH の有効性があるとは言い難い．

Publication Types:
* Clinical Trial
* Randomized Controlled Trial

MeSH Terms:
* Adult
* Female
* Humans
* Male
* Manipulation, Spinal*
* Middle Aged
* Research Support, Non-U.S. Gov't
* Tension Headache/therapy*
* Treatment Outcome

5) Boline PD, Kassak K, Bronfort G, Nelson C, Anderson AV. Spinal 　 manipulation vs. amitriptyline for the treatment of chronic tension- 　 type headaches: a randomized clinical trial. J Manipulative Physiol 　 Ther. 1995 Mar-Apr;18(3):148-54.
論文抄録	OBJECTIVE: To compare the effectiveness of spinal manipulation and pharmaceutical treatment (amitriptyline) for chronic tension-type headache. DESIGN: Randomized controlled trial using two parallel groups. The study consisted of a 2-wk baseline period, a 6-wk treatment period and a 4-wk posttreatment, follow-up period. SETTING: Chiropractic college outpatient clinic. PATIENTS: One hundred and fifty patients between the ages of 18 and 70 with a diagnosis of tension-type headaches of at least 3 months' duration at a frequency of at least once per wk. INTERVENTIONS: 6 wk of spinal manipulativetherapy provided by chiropractors or 6 wk of amitriptyline treatment managed by a medical physician. MAIN OUTCOME MEASURES: Change in patient-reported daily headache intensity, weekly headache frequency, over-the-counter medication usage and functional health status (SF-36). RESULTS: A total of 448 people responded to the recruitment advertisements; 298 were excluded during the screening process. Of the 150 patients who were enrolled in the study, 24 (16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%) from the amitriptyline therapy group. During the treatment period, both groups improved at very similar rates in all primary outcomes. In relation to baseline values at 4 wk after cessation of treatment, the spinal manipulation group showed a reduction of 32% in headache intensity, 42% in headache frequency, 30% in over-the-counter medication usage and an improvement of 16% in functional health status. By comparison, the amitriptyline therapy group showed no improvement or a slight worsening from baseline values in the same four major outcome measures. Controlling for baseline differences, all group differences at 4 wk after cessation of therapy were considered to be clinically important and were statistically significant. Of the patients who finished the study, 46 (82.1%) in the amitriptyline therapy group reported side effects that included drowsiness, dry mouth and weight gain. Three patients (4.3%) in the spinal manipulation group reported neck soreness and stiffness. CONCLUSIONS: The results of this study show that spinal manipulative therapy is an effective treatment for tension headaches. Amitriptyline therapy was slightly more effective in reducing pain at the end of the treatment period but was associated with more side effects. Four weeks after the cessation of treatment, however, the patients who received spinal manipulative therapy experienced a sustained therapeutic benefit in all major outcomes in contrast to the patients that received amitriptyline therapy, who reverted to baseline values. The sustained therapeutic benefit associated with spinal manipulation seemed to result in a decreased need for over-the-counter medication. There is a need to assess the effectiveness of spinal manipulative therapy beyond four weeks and to compare spinal manipulative therapy to an appropriate placebo such as sham manipulation in future clinical trials.
文献 PubMed − ID	PMID: 7790794
エビデンスレベル	Ib
文献タイトル ( 日本語 )	慢性緊張型頭痛（ CTTH ）における指圧と amitriptyline 治療：無作為比較臨床試験
目的	CTTH における指圧療法あるいは amitriptyline を用いた薬理学療法の予防法の有効性を検証すること．
研究デザイン	無作為二重盲検対照試験（ Randomized, double-blind, controlled study ）
研究施設	Chiropractic college outpatient clinic
研究期間	N/A
対象患者	150 人の CTTH 患者（少なくとも３ヶ月，一週間に１回の頭痛を有する CTTH ）
介入	6 週間の指圧療法あるいは amitriptyline を用いた薬物療法を平行して２群で行った．
主要評価項目とそれに用いた統計学的手法	日々の頭痛強度の変化，１週間あたりの頭痛頻度，鎮痛剤の服用回数， SF-36 を用いた全般的な健康状態
結果	治療期間中には両群ともに同様な頭痛改善率を示したが，治療終了 4 週後の時点では，指圧治療群では，治療開始前に比べ頭痛強度は 32%, 頭痛頻度は 42%, 鎮痛剤の服用回数は 30%, 健康状態も 16% 改善したが，薬物治療群では有意な改善は得られなかった．薬物治療群では眠気，口腔内乾燥，体重増加など 82.1% の副作用を，指圧群では，頸部痛や硬直感を 4.3% に認めた．
結論	指圧療法は， CTTH の予防法として有効である． Amitriptyline 治療は，治療終了時では指圧療法に比し頭痛回数という点ではより有効であったが，より多くの副作用が認められた．しかし，治療終了後４週間後の時点では，指圧治療群の方がより持続した治療効果を得られた .
備考	Publication Types: * Clinical Trial * Randomized Controlled Trial MeSH Terms: * Adult * Aged * Amitriptyline/therapeutic use* * Chiropractic/methods* * Comparative Study * Drugs, Non-Prescription/therapeutic use * Female * Follow-Up Studies * Humans * Male * Middle Aged * Pain Measurement * Research Support, Non-U.S. Gov't * Tension Headache/drug therapy * Tension Headache/therapy* Substances: * Drugs, Non-Prescription * Amitriptyline
作成者	飯塚高浩

6) Bogaards MC, ter Kuile MM. Treatment of recurrent tension 　 headache: a meta-analytic review. Clin J Pain. 1994 Sep;10 (3):174- 　 90.
論文抄録	The primary aim of this study was to investigate which treatment, patient, and study characteristics are related to treatment outcome in tension headache. Literature on the subject was obtained by searching for articles published in English through CD-rom Compact Cambridge and PSYCHLIT (1970/1993) on the subjects of headache and tension or muscle contraction in combination with therapy or treatment. Inclusion criteria were prospective design, tension headache, > or = five subjects per condition; pre- and posttreatment scores available, subjects older than 16 years. Each article was independently reviewed and its data encoded by the two authors. Finally, 78 articles with 175 treated and nontreated conditions (total of 2,866 patients) were selected for this study. Meta-analysis revealed that cognitive therapy, relaxation, or electromyelographic (EMG) biofeedback alone or in combination with relaxation were superior to no treatment and to pseudo/placebo therapy. Pharmacological and other therapies were better than no treatment. However, restricting the analyses to studies using a headache diary, the results of pharmacological therapy were comparable to those of placebo therapy. Moreover, a better treatment outcome was found in studies with a relatively short duration of headache complaints (r -0.31) and with a relatively younger patient sample (r = -0.22). The year of publication was negatively related with improvement (r = -0.36). No relationship between treatment outcome and other treatment characteristics (duration, transfer of treatment), patient characteristics (gender, method of patient recruitment), and study characteristics (internal validity of the study, criteria for diagnosing tension headache, number of patients, drop-outs) was found. These findings suggest that treatment outcome may be affected more by patient characteristics than by treatment characteristics. Finally, some practical and research implications of these findings are discussed.
文献 PubMed − ID	PMID:7833575
エビデンスレベル	Ia
文献タイトル ( 日本語 )	再発性緊張型頭痛の治療：メタ解析
目的	どのような治療法，患者，研究デザインが最も緊張型頭痛の予後に関連しているかを明らかにすること．
研究デザイン	1970 年から 1993 年にかけて CD-rom Compact Cambridge and PSYCHLIT に掲載された英語で書かれた論文検索で， headache と tension あるいは muscle contraction を therapy あるいは treatment を組み合わせてで検索した． Inclusion 基準として，前向き研究，緊張型頭痛， 5 人以上の対象患者であること，治療前後のスコアーが記載されていること，患者は 16 歳以上であることなどである．２人の reviewers によって選出された．
研究施設	N/A
研究期間	N/A
対象患者	N/A
介入	N/A
主要評価項目とそれに用いた統計学的手法	N/A
結果	最終的に 78 編の論文が選出された． ( 合計 2,866 人の患者 ) ．メタ解析の結果，認知治療，緩和治療，筋電図生体フィードバック療法のみ，あるいは緩和療法との併用療法が未治療群やプラセボ治療群より勝っていた．薬物治療あるいはその他の治療は，未治療より勝っていなかった．しかし，頭痛日記を用いている試験結果に絞ると，薬物治療成績は，プラセボ効果と同等であり，更に，頭痛持続期間が短い場合や若年者では薬物療法の治療成績が勝っていた．論文掲載年度と治療成績には逆相関がみられた．治療成績と，治療要因（治療の持続期間，治療法），患者要因，試験の信頼度（患者の性，患者の登録法），試験方法（緊張型頭痛の診断基準，患者数，脱落率）には有意な関係がなかった．
結論	治療予後は，治療法自体より患者の特徴によって影響を受ける可能性がある．
備考	Publication Types: * Meta-Analysis MeSH Terms: * Humans * Recurrence * Tension Headache/drug therapy * Tension Headache/psychology * Tension Headache/therapy*
作成者	飯塚高浩

7) Hansen PE , Hansen JH. Acupuncture treatment of chronic tension 　 headache--a controlled cross-over trial. Cephalalgia. 1985 　 Sep;5(3):137-42.
論文抄録	In a controlled trial the effect of traditional Chinese acupuncture v. placebo acupuncture was evaluated in 18 patients with chronic tension headache (mean disease duration 15 years). All patients suffered from daily or frequently recurring headache, the intensity of which was recorded by the patient over a period of 15 weeks. Each patient was treated by traditional Chinese acupuncture as well as by placebo acupuncture in a cross-over design following randomization. Each period of treatment comprised six treatments. Traditional Chinese acupuncture was found to be significantly more pain-relieving than placebo acupuncture, according to the pain registration of the patients themselves. The pain reduction was 31%. Acupuncture is therefore found to be a reasonable treatment for chronic tension headache.
文献 PubMed − ID	PMID:3899369
エビデンスレベル	Ib
文献タイトル ( 日本語 )	慢性緊張型頭痛における鍼灸治療：プラセボ対照交差試験
目的	伝統的中国式鍼灸の有効性を検証する．
研究デザイン	無作為二重盲検プラセボ対照交差試験（ Randomized, double-blind, placebo-controlled crossover study ）
研究期間	1981 年３月から１２月
対象患者	１年以上の罹病期間を有する慢性筋収縮性頭痛患者 18 人
介入	伝統的中国式の鍼灸治療とプラセボ鍼灸治療をそれぞれ３週間ずつ行い，有効性について評価した．
主要評価項目とそれに用いた統計学的手法	頭痛の全くない日数，通常の頭痛より軽い頭痛を認める日数，通常の頭痛を認める日数，通常より高度な頭痛を認める日数をもとに， period index(PI) を算出し評価した．
結果	伝統的中国式の鍼灸治療群はプラセボ群に比べ有意に改善した．
結論	伝統的中国式の鍼灸治療群は有効な治療法である．
コメント	症例数も少ない．
備考	Publication Types: * Clinical Trial * Randomized Controlled Trial MeSH Terms: * Acupuncture Therapy* * Chronic Disease * Clinical Trials * Headache/therapy* * Humans
作成者	飯塚高浩

8) Cerbo R, Barbanti P, Fabbrini G, Pascali MP, Catarci T. Amitriptyline 　 is effective in chronic but not in episodic tension-type headache: 　 pathogenetic implications. Headache. 1998 Jun;38(6):453-7.
論文抄録	The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.
文献 PubMed − ID	PMID: 9664750
エビデンスレベル	IIb
文献タイトル ( 日本語 )	Amitriptyline は慢性緊張型頭痛 (CTTH) には有効であるが，発作性緊張型頭痛 (ETTH) には有効でない：病因論的に示唆にとむ知見である．
目的	ETTH における Amitriptyline の有効性を検証すること．
研究デザイン	オープンラベル試験（ Open-label study ）
研究施設	University of Rome La Sapienza, Roma, Italy
研究期間	N/A
対象患者	CTTH （ 48 人）と ETTH （ 34 人）の合計 82 人である．
介入	治療開始前 4 週間， 12 週間の治療期間，治療終了後の 4 週間１ヶ月毎に評価し，有効性について検討した．
主要評価項目とそれに用いた統計学的手法	主要評価項目は，頭痛頻度，頭痛持続時間，鎮痛剤服用量である．統計学的には， ANOVA, Wilcoxon test with Bonferroni's correction を用いた．
結果	CTTH では，頭痛頻度，頭痛持続時間，鎮痛剤服用量において amitriptyline 治療により有意に減少したが， ETTH では認めなかった．
結論	amitriptyline 治療は ETTH では有効ではない．
備考	MeSH Terms: * Adrenergic Uptake Inhibitors/therapeutic use* * Amitriptyline/therapeutic use* * Analgesics/therapeutic use * Chronic Disease * Humans * Recurrence * Tension Headache/classification * Tension Headache/drug therapy* * Tension Headache/etiology Substances: * Adrenergic Uptake Inhibitors * Analgesics * Amitriptyline
作成者	飯塚高浩

10) Martin-Araguz A, Bustamante-Martinez C, de Pedro-Pijoan JM . 　 Treatment of chronic tension type headache with mirtazapine and 　 amitriptyline. Rev Neurol 2003 Jul 16-31;37(2):101-5
論文抄録	INTRODUCTION: The mechanisms at play in the production of tension type headaches (TTH) are partially unknown. Some of the aspects that have been discussed in connection with this issue include genetic, vascular and biochemical factors and even a predisposition of certain personalities to suffer from this kind of pain. Yet, the relation between neurotransmitters like noradrenalin (NAd) and serotonin (5 HT) and chronic TTH (CTTH) seems to be quite clear and hence the use of antidepressants that act on these substances in the pharmacological treatment of CTTH. In this study, the qualitative and quantitative efficiency of amitriptyline is compared with that of mirtazapine (two antidepressants that act on NAd and 5 HT) in the prophylaxis of CTTH. PATIENTS-AND-METHODS: A sample of 60 patients with CTTH criteria was divided into two groups, and subjects were administered one of the drugs at 50% random for six months. Group I was administered 25 mg of amitriptyline and group II received 30 mg of mirtazapine, both given in a single night time oral dose. Later, the two groups were compared before and after treatment, taking into account the following aspects: objective and subjective improvements, depression criteria according to the Hamilton 17 coefficient, reduction in the amount of pain killers taken, and the side effects produced by the two drugs. RESULTS: Both groups of patients presented depression criteria, which improved after taking the drugs, without any objective differences between the two forms of therapy, although the subjective feeling of improvement was greater with mirtazapine. In both groups there was a significant reduction in the usual consumption of analgesics after the prophylaxis. Side effects with both antidepressants were relatively frequent, but well tolerated, and the most common were a dry mouth and drowsiness. There were significantly fewer in the group of patients treated with mirtazapine than in those who received amitriptyline. CONCLUSIONS: First, depression and CTTH clearly coexist and that there is a certain dysphoric component associated to suffering chronic headache. Second, mirtazapine has proved to be as efficient in the treatment of CTTH as amitriptyline, but has significantly fewer side effects, probably because it acts more selectively on the brain receptors. It could, therefore, be a drug worth considering for use in the prophylaxis of chronic TTH.
文献 PubMed − ID	PMID: 12938066
エビデンスレベル	Ib
文献タイトル ( 日本語 )	CTTH に対するミルタザピンとアミトリプチンによる治療
目的	CTTH に対するミルタザピンの効果を EBM のあるアミトリプチリンと比較検討する．
研究デザイン	無作為二重盲検プラセボ対照交差試験（ Randomized, double-blind, placebo-controlled crossover study ）
研究施設	Servicio de Neurologia, Hospital del Aire, Departamento de Medicina, Universidad Complutense de Madrid
研究期間	6 ヵ月間
対象患者	CTTH の診断基準に合致した 60 名
介入	薬物投与
主要評価項目とそれに用いた統計学的手法	客観的，主観的な改善効果， Hamilton17 によるうつの評価，鎮痛薬の使用減少と副作用を評価項目とした．
結果	ミルタザピン，アミトリプチンともに CTTH のうつを中心とした改善効果および鎮痛薬の使用減少を得たが，主観的な改善効果はミルタザピンがアミトリプチンに有意に優っていた．また , 副作用は両者とも口腔乾燥と傾眠状態であったが，投与中止にいたるようなものではなかった．
結論	CTTH に対するミルタザピンの効果はアミトリプチリンに優る．
コメント	ミルタザピンは本邦未承認
備考	Publication Types: Clinical Trial Randomized Controlled Trial MeSH Terms: Adult Amitriptyline/adverse effects Amitriptyline/therapeutic use Comparative Study Double-Blind Method English Abstract Fatigue/chemically induced Female Humans Male Mianserin/adverse effects Mianserin/analogs & derivatives Mianserin/therapeutic use* Middle Aged Norepinephrine/physiology Serotonin/physiology Tension Headache/drug therapy* Tension Headache/physiopathology Treatment Outcome *Xerostomia/chemically induced
作成者	平田幸一

11) Kubitzek F, Ziegler G, Gold MS, Liu JM, Ionescu E . Low-dose 　 diclofenac potassium in the treatment of episodic tension-type 　 headache. Eur J Pain 2003;7(2):155-62
論文抄録	BACKGROUND: Several clinical trials have demonstrated that low doses of non-steroidal anti-inflammatory drugs relieve episodic tension-type headache (ETH). AIMS: The aims of this placebo-controlled study were to determine whether single doses of diclofenac-K 12.5 and 25mg effectively relieve ETH in adults and to compare it to ibuprofen 400mg. METHODS: A single-dose multicentre, randomised, double-blind, double-dummy, clinical trial was conducted at 22 primary care centres in Germany . All subjects had a history of ETH according to the classification of the International Headache Society. Of 684 subjects randomised, 620 used the study drugs for an episode of tension headache occurring within one month after enrolment: diclofenac-K 12.5mg (n=160), diclofenac-K 25mg (n=156), ibuprofen 400mg (n=151) and placebo (n=153). The primary efficacy variable was total pain relief, calculated as the time-weighted sum of the pain relief assessments from baseline to the 3h evaluation time (TOTPAR-3). RESULTS: For TOTPAR-3, all active treatments were superior to placebo; no statistically significant difference between the three active treatments could be detected. A similar pattern was also observed with regard to TOTPAR-6 (6h evaluation time), > or =50%maxTOTPAR at 3 and 6h, weighted pain intensity difference at 3 and 6h (SPID-3; SPID-6), percentage of patients with complete headache relief at 2h, end of study global evaluation and time to rescue medication. The number-needed-to-treat (NNT) at 6h was 4.5 (2.9-9.2) in the ibuprofen 400mg group, 4.0 (2.8-7.3) in the diclofenac-K 12.5mg group and 3.9 (2.7-7.1) in the diclofenac-K 25mg group. These differences were not statistically significant.CONCLUSION: Diclofenac-K, administered as single doses of 12.5 and 25mg effectively relieves ETH and is comparable to ibuprofen 400mg.
文献 PubMed − ID	PMID: 12600797
エビデンスレベル	Ib
文献タイトル ( 日本語 )	反復発作性緊張型頭痛の治療における低用量ジクロフェナクカリウム
目的	イブプロフェン 400mg と比較したジクロフェナク -K12.5mg 及び 25mg は成人における ETH に対する有用性の検討
研究デザイン	無作為二重盲検ダブルダミー単回投与多施設臨床試験（ :A single-dose multicentre, randomised, double-blind, double-dummy, clinical trial ）
研究施設	ドイツ 22 ヶ所のプライマリーケアセンター
研究期間	N/A
対象患者	IHS 診断基準に則り ETH の病歴を持つ患者 684 名
介入	ジクロフェナク -K12.5mg （ n ＝ 160 ），ジクロフェナク 25mg （ n=156 ），イブプロフェン 400mg （ n=151 ）およびプラセボ（ n=153 ）．
主要評価項目とそれに用いた統計学的手法	プライマリーの評価はトータルの頭痛消失であり，ベースラインから 3 時間の評価時間までの頭痛消失評価の時加重合計として計算（ TOTPAR-3 ）した．
結果	TOTPAR-3 において，全ての実薬治療はプラセボに優っていた． 3 つの実薬群では統計学的有意差は無かった． TOTPAR-6 （評価時間 6 時間） 3 時間および 6 時間の 50 ％ maxTOTPAR より大あるいは同等でも類似の結果が観察されており，加重頭痛強度の 3 時間あるいは 6 時間での変異（ SPID-3 ， SPID-6 ）， 2 時間での頭痛完全消失の患者の割合，グローバル評価，およびレスキュー治療までの時間にも有意差はなかった． 6 時間時の number-needed-to-treat （ NNT ）はイブプロフェン群で 4.5 （ 2.9-9.2 ），ジクロフェナク -K 12.5mg 群で 4.0 （ 2.8-7.3 ），ジクロフェナク -K25mg 群で 3.9 （ 2.7-7.1 ）であり，これらに有意差は無かった．
結論	単回で投与されたジクロフェナク -K12.5mg および 25mg は ETH を効果的に緩和し，イブプロフェン 400mg と同等の効果が認められた．
コメント	用量設定まで行った RCT ．よくデザインされた多施設研究．
備考	Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial MeSH Terms: Adult Anti-Inflammatory Agents, Non-Steroidal/administration & dosage Anti-Inflammatory Agents, Non-Steroidal/adverse effects Diclofenac/administration & dosage* Diclofenac/adverse effects Dose-Response Relationship, Drug Double-Blind Method Female Humans Ibuprofen/administration & dosage Ibuprofen/adverse effects Male Middle Aged Pain Measurement Palliative Care Research Support, Non-U.S. Gov't Salvage Therapy Tension Headache/drug therapy* Tension Headache/physiopathology Time Factors Treatment Outcome
作成者	平田幸一

12) Prior MJ, Cooper KM, May LG, Bowen DL . Efficacy and safety of 　 acetaminophen and naproxen in the treatment of tension-type 　 headache. A randomized, double-blind, placebo-controlled trial. 　 Cephalalgia 2002 Nov;22(9):740-8
論文抄録	The objective of this study was to evaluate and compare the efficacy and safety of single doses of acetaminophen (paracetamol) 1000 mg and naproxen 375 mg vs. placebo over a six-hour period in the treatment of tension-type headache. The treatments were compared in a randomized, double-blind, multicentre, placebo-controlled study. Efficacy was evaluated using four standard analgesic summary endpoints (the sum of pain intensity differences from baseline, the maximum pain intensity from baseline, the sum of the pain relief scores, and the maximum pain relief score). Both acetaminophen 1000 mg and naproxen 375 mg were significantly superior to placebo (P<or=0.009 and P<or=0.021, respectively) but not significantly different from each other (P>or=0.498) for these four endpoints. For example, the mean sum of pain intensity differences from baseline was 9.14+/-0.34 for acetaminophen 1000 mg and 8.81+/-0.35 for naproxen 375 mg compared with 7.42+/-0.34 for placebo. Other efficacy endpoints (percentage of responders (pain reduced to none) at two hours, onset of meaningful relief, time to use of rescue medication and subject's overall impression of study medication) showed similar trends. A significantly larger mean pain intensity difference from baseline was observed for acetaminophen 1000 mg (1.13) than for naproxen 375 mg (0.95) (P=0.036) at one hour after treatment. There was no significant difference among the treatment groups in the incidence of adverse events (P=0.730). In summary, the results of this well-controlled, double-blind study demonstrate that over-the-counter acetaminophen 1000 mg and prescription naproxen 375 mg are effective and well tolerated in the treatment of tough (moderate-to-severe) tension-type headache.
文献 PubMed − ID	PMID: 12421160
エビデンスレベル	Ia
文献タイトル ( 日本語 )	アセトアミノフェンおよびナプロキセンの緊張型頭痛に対する効果と安全性．無作為二重盲検プラセボ対照試験
目的	緊張型頭痛の治療における 6 時間での効果，安全性，について単回投与したアセトアミノフェン（パラセタモール） 1,000mg およびナプロキセン 375mg をプラセボと比較
研究デザイン	無作為化二重盲検多施設プラセボ対照比較試験（ randomized, double-blind, multicentre, placebo-controlled study ）単回投与試験
研究施設	Research & Development, McNeil Consumer & Specialty Pharmaceuticals, Fort Washington
研究期間	N/A
対象患者	中等度〜重症の緊張型頭痛
介入	アセトアミノフェン 1,000mg 群ナプロキセン 375mg 群プラセボ群　の薬物治療
主要評価項目とそれに用いた統計学的手法	4 つの標準的な鎮痛薬のサマリーエンドポイント（ベースラインと比較した痛みの強度の合計，ベースラインと比較した最も強いとされる痛みの強度，頭痛消失スコアの合計，頭痛消失スコアの最高点）を用いて評価
結果	アセトアミノフェン 1,000mg 群とナプロキセン 375mg 群はいずれもプラセボ群に有意に優っていたが（それぞれＰ＜ or ＝ 0.009 ，Ｐ <or=0.021 ） 4 つのエンドポイントではいずれでも有意差は無かった．例えば，ベースラインからの頭痛強度変化の合計の平均はアセトアミノフェン 1,000mg 群で 9.14+/-0.34 ，ナプロキセン 375mg 群で 8.81+/-0.35 であり，プラセボは 7.42+/-0.34 であった．その他の効果エンドポイント（ 2 時間での頭痛消失，有意な頭痛緩解のオンセット，レスキュー治療が必要になるまでの時間，および被験者の試験薬にたいする全体的な印象）については似たような傾向が示された．ベースラインからの頭痛強度の変化の平均が有意に大きかったのはアセトアミノフェン 1,000mg 群であり（ 1.13 ），ナプロキセン 375mg 群（ 0.95 ）を治療後 1 時間で上回った．（ P=0.036 ）治療群で副作用発現率に有意差は無かった．（ P=0.730 ）
結論	本試験により，中等度〜重症の緊張型頭痛の治療において， OTC アセトアミノフェン 1,000mg と処方薬ナプロキセン 375mg は共に有効であり，忍容性が高いことが示された．
コメント	OTC の問題を考慮する上でも重要なアセトアミノフェンとナプロキセンの用量比較を包含した試験．
備考	Publication Types: Clinical Trial Randomized Controlled Trial MeSH Terms: Acetaminophen/adverse effects Acetaminophen/therapeutic use* Adolescent Adult Aged Aged, 80 and over Comparative Study Double-Blind Method Female Humans Least-Squares Analysis Male Middle Aged Naproxen/adverse effects Naproxen/therapeutic use Research Support, Non-U.S. Gov't Statistics, Nonparametric Tension Headache/drug therapy Tension Headache/physiopathology Treatment Outcome
作成者	平田幸一

13) Bigal ME, Bordini CA, Speciali JG . Intravenous chlorpromazine in 　 the acute treatment of episodic tension-type headache: a 　 randomized, placebo controlled, double-blind study. Arq 　 Neuropsiquiatr 2002 Sep;60(3-A):537-41
論文抄録	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
文献 PubMed − ID	PMID: 12244386
エビデンスレベル	Ib
文献タイトル ( 日本語 )	反復発作性緊張型頭痛の急性期治療における静注クロロプロマジン：無作為プラセボ対照二重盲検試験
目的	反復発作性緊張型頭痛の急性期治療に対するクロロプロマジンの効果について，無作為プラセボ対照二重盲検比較試験で検討
研究デザイン	無作為二重盲検プラセボ対照試験（ Randomized, double-blind, placebo-controlled study ）
研究施設	Department of Neurology, School of Medicine at Ribeirao Preto , University of Sao Paulo
研究期間	N/A
対象患者	反復発作性緊張型頭痛患者 30 名
介入	プラセボ群（生理食塩水 10mｌ静注）クロロプロマジン群（ 0.1mg/kg 静注）の両薬剤投与
主要評価項目とそれに用いた統計学的手法	鎮痛薬評価における 7 つのパラメータ（痛み， Therapeutic Gain, 治療を必要とした患者数，再発率，レスキュー薬剤の使用）
結果	クロロプロマジン群ではプラセボ群に比し有意に痛みが改善された（ P ＜ 0.05 および P ＜ 0.01 ） Therapeutic Gain は 30 分で 36.7 ％， 60 分で 56.6 ％であった． number needed to treat ： NNT （ therapeutic gain を患者一人の治療に必要な症例数からみたもの）は 30 分で 2.7 ， 60 分で 1.8 であった．クロロプロマジン群では再発率およびレスキュー薬剤使用の減少もみられた．
結論	静注クロロプロマジンは緊張型頭痛の痛み緩和に有効な薬剤と結論する．
コメント	将来的に頭痛救急医療で考慮すべき治療法の提示．
備考	Publication Types: Clinical Trial Randomized Controlled Trial MeSH Terms: Acute Disease Adult Chlorpromazine/administration & dosage Dopamine Antagonists/administration & dosage Double-Blind Method Female Humans Injections, Intravenous Male Recurrence Tension Headache/drug therapy *Treatment Outcome
作成者	平田幸一

14) Singh NN, Misra S . Sertraline in chronic tension-type headache. 　 J Assoc Physicians India 2002 Jul;50:873-8
論文抄録	OBJECTIVES: To study the effect of Sertraline, a selective serotonin reuptake inhibitor in chronic tension type headache (CTTH) in a double blind placebo controlled randomized trial. MATERIAL-AND-METHODS: The study design was a double blind placebo controlled randomized study of 50 patients, over a period of 10 weeks including run-in period of two weeks, treatment period four weeks, and follow-up four weeks. The diagnosis of CTTH was based on criteria given by International Headache Society (IHS). The overall response was graded in terms of headache index, analgesic intake per week and percentage reduction in headache frequency using chi-square and 't' test. Anxiety and depression was assessed using Hamilton Rating Scale. RESULTS: The mean analgesic intake per week declined from 4.34 +/- 0.736 tab/week to 1.07 +/- 0.592 tab/week in sertraline group (p < 0.01) while reduction in placebo group was not significant (3.98 +/- 0.729 tab/week to 2.94 +/- 0.665 tab/week) (p > 0.05). The reduction in headache index and percentage reduction in frequency of headache was not significant in drug treatment group. Side effects were seen in 24.4% of patients nausea, nervousness and dizziness being the commonest. CONCLUSION: The drug treatment group showed a significant decline in analgesic intake per week. The study result shows that sertraline can be a useful alternative to amitryptiline in those patients who fail to respond or cannot tolerate it.
文献 PubMed − ID	PMID: 12126338
エビデンスレベル	Ib
文献タイトル ( 日本語 )	慢性緊張型頭痛における Setraline
目的	慢性緊張型頭痛（ CTTH ）に対する Sertraline （選択的セロトニン再取り込み阻害剤）の効果を二重盲検プラセボ対照無作為化試験で検討する
研究デザイン	無作為二重盲検プラセボ対照試験（ Randomized, double-blind, placebo-controlled study ）
研究施設	Department of Neurology, Institute of Medical Sciences, Banaras Hindu University
研究期間	導入期間 2 週間，治療期間 4 週間，フォローアップ期間 4 週間を含めた 10 週間実施．
対象患者	IHS 診断基準に基づいて診断した CTTH 患者 50 名
介入	二重盲検プラセボ対照薬物投与
主要評価項目とそれに用いた統計学的手法	頭痛インデックスの概括反応率， 1 週間の鎮痛剤服用，頭痛頻度におけるパーセンテージ減少を chi-square および t-test を用いてグレード化．不安およびうつは Hamilton Rating Scale で評価．
結果	Sertraline 群において 1 週間の平均鎮痛薬服用量は 4.34+/-0.736 錠から 1.07+/-0.592 錠に減少（ P<0.01 ），プラセボ群では特に有意な減少は見られなかった（ 3.98+/-0.729 錠から 2.94 ＋ /-0.665 錠）．（ P ＞ 0.05 ）頭痛インデックスの減少および頭痛頻度の割合減少は治療群において有意な差はなかった．副作用は 24.4 ％であり，最も多かったものは悪心，神経過敏，めまいであった．
結論	治療薬剤は有意に 1 週間の鎮痛薬使用量を減少させた． Sertraline はアミトリプチリンが無効あるいは忍容性が低い場合の有用な代替治療である．
コメント	現在エビデンスの少ない SSRI の有効性を示した試験．
備考	Publication Types: Clinical Trial Randomized Controlled Trial MeSH Terms: Adult Chronic Disease Double-Blind Method Female Humans Male Serotonin Uptake Inhibitors/therapeutic use Sertraline/therapeutic use Tension Headache/drug therapy *Treatment Outcome
作成者	平田幸一

15) Bronfort G, Assendelft WJ, Evans R, Haas M, Bouter L . Efficacy of 　 spinal manipulation for chronic headache: a systematic review . J 　 Manipulative Physiol Ther 2001 Sep;24(7):457-66
論文抄録	BACKGROUND: Chronic headache is a prevalent condition with substantial socioeconomic impact. Complementary or alternative therapies are increasingly being used by patients to treat headache pain, and spinal manipulative therapy (SMT) is among the most common of these. OBJECTIVE: To assess the efficacy/effectiveness of SMT for chronic headache through a systematic review of randomized clinical trials. STUDY SELECTION: Randomized clinical trials on chronic headache (tension, migraine and cervicogenic) were included in the review if they compared SMT with other interventions or placebo. The trials had to have at least 1 patient-rated outcome measure such as pain severity, frequency, duration, improvement, use of analgesics, disability, or quality of life. Studies were identified through a comprehensive search of MEDLINE (1966-1998) and EMBASE (1974-1998). Additionally, all available data from the Cumulative Index of Nursing and Allied Health Literature, the Chiropractic Research Archives Collection, and the Manual, Alternative, and Natural Therapies Information System were used, as well as material gathered through the citation tracking, and hand searching of non-indexed chiropractic, osteopathic, and manual medicine journals. DATA EXTRACTION: Information about outcome measures, interventions and effect sizes was used to evaluate treatment efficacy. Levels of evidence were determined by a classification system incorporating study validity and statistical significance of study results. Two authors independently extracted data and performed methodological scoring of selected trials. DATA SYNTHESIS: Nine trials involving 683 patients with chronic headache were included. The methodological quality (validity) scores ranged from 21 to 87 (100-point scale). The trials were too heterogeneous in terms of patient clinical characteristic, control groups, and outcome measures to warrant statistical pooling. Based on predefined criteria, there is moderate evidence that SMT has short-term efficacy similar to amitriptyline in the prophylactic treatment of chronic tension-type headache and migraine. SMT does not appear to improve outcomes when added to soft-tissue massage for episodic tension-type headache. There is moderate evidence that SMT is more efficacious than massage for cervicogenic headache. Sensitivity analyses showed that the results and the overall study conclusions remained the same even when substantial changes in the prespecified assumptions/rules regarding the evidence determination were applied. CONCLUSIONS: SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has an effect comparable to commonly used first-line prophylactic prescription medications for tension-type headache and migraine headache. This conclusion rests upon a few trials of adequate methodological quality. Before any firm conclusions can be drawn, further testing should be done in rigorously designed, executed, and analyzed trials with follow-up periods of sufficient length.
文献 PubMed − ID	PMID: 11562654
エビデンスレベル	Ia
文献タイトル ( 日本語 )	脊柱手技療法（ SMT ）の慢性頭痛に対する効果 / 有効性の検討：系統的レビューによる
目的	無作為化臨床試験の系統的レビューによる SMT の慢性頭痛に対する効果 / 有効性の検討
研究デザイン	無作為二重盲検プラセボ対照交差試験（ Randomized, double-blind, placebo-controlled crossover study ）
研究施設	系統的レビュー
研究期間	N/A
対象患者	9 試験， 683 名の慢性頭痛患者（緊張型頭痛，片頭痛，頸原生頭痛）
介入	脊柱手技療法（ SMT ）
主要評価項目とそれに用いた統計学的手法	患者の主観による結果判定（痛みの重症度，頻度，持続時間，改善，鎮痛薬の使用，支障度あるいは QOL ）． MEDLINE （ 1966-1998 ）と EMBASE （ 1974-1998 ）を使用．エビデンスレベルは試験の妥当性と試験結果の統計学的優位性を合体した分類システムを用いて検討． 2 名の著者がそれぞれデータを抽出し，選択した試験の方法論をスコア化．
結果	SMT は慢性緊張型頭痛および片頭痛の予防治療としてアミトリプチリンと同等の短期的効果があることについては適当なレベルのエビデンスが存在する． SMT は反復発作性緊張型頭痛の治療で柔組織マッサージに追加された場合には，結果を改善しない． SMT は頸原生頭痛についてはマッサージより効果があるという事については適当なレベルのエビデンスが存在する．感度分析により，エビデンスの検討に関し予め特定した仮定条件 / ルールが摘要された場合にでも結果と試験の概括試験結論は同じであるという事が示された．
結論	SMT は頸原性頭痛に対しマッサージより効果があることが判明した．また SMT は緊張型頭痛および片頭痛に対しファーストラインとされる予防療法の処方薬と同等の効果を持つ事も判明した．
コメント	SMT を頸原性頭痛，緊張型頭痛に効果があることを示したメタアナライシス．
備考	Publication Types: Meta-Analysis MeSH Terms: Chiropractic/methods* Chronic Disease Confounding Factors (Epidemiology) Databases, Bibliographic Humans Manipulation, Spinal Migraine/therapy Pain Measurement Physical Therapy Techniques Randomized Controlled Trials Research Design Research Support, Non-U.S. Gov't Tension Headache/therapy* *Treatment Outcome
作成者	平田幸一

17) Ashina M, Lassen LH, Bendtsen L, Jensen R, Olesen J. Effect of 　 inhibition of nitric oxide synthase on chronic tension-type 　 headache: a randomised crossover trial.
論文抄録	BACKGROUND: Studies in animals have shown that nitric oxide plays an important part in central sensitisation and that inhibitors of nitric oxide synthase (NOS) decrease sensitisation in models of persistent pain. The efficacy of inhibitors of NOS has not been tested in patients with tension-type chronic headache. We aimed to show whether N(G)-monomethyl-L-arginine hydrochloride (L-NMMA), an inhibitor of NOS, is effective in relieving pain in such patients. METHODS: We undertook a randomised double-blind, crossover trial of 16 patients with chronic-tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week in a randomized order. Headache intensity was measured on a 100 mm visual analogue scale, and on a verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. The primary endpoint was reduction of pain intensity on the visual analogue scale by the active treatment compared with placebo. FINDINGS: L-NMMA reduced pain intensity on the visual analogue scale significantly more than placebo: 120 min after start of treatment, the mean pain score was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p=0.01). Pain intensity on the verbal rating scale was also significantly lower for treatment with L-NMMA than for treatment with placebo (p=0.02). INTERPRETATION: Inhibition of NOS had an analgesic effect in chronic tension-type headache. Further tests are required before clinical application.
文献 PubMed − ID	PMID:9929022
エビデンスレベル	Ib
文献タイトル ( 日本語 )	慢性緊張型頭痛における NOS 阻害薬の効果：無作為交差試験
目的	慢性緊張型頭痛 (CTTH) における NOS 阻害薬である L-NMMA 静脈投与の有効性を検証すること．
研究デザイン	無作為二重盲検プラセボ対照交差試験（ Randomized, double-blind, placebo-controlled crossover study ）
研究施設	Glostrup Hospital , University of Copenhagen , Denmark
研究期間	N/A
対象患者	16 人の CTTH 患者
介入	N/A
主要評価項目とそれに用いた統計学的手法	投与 30 分後， 60 分後， 120 分後の頭痛強度を visual analogue scale(VAS) と verbal rating scale(VRS) で評価した． VAS は independent- ｔ test を， VRS は Wilcoxon signed-ranks tests を用いて解析した．
結果	L-NMMA 静注の方が偽薬に比べ有効であった．
結論	NOS inhibitor である L-NMMA は慢性型緊張型頭痛に有効である．
備考	Publication Types: * Clinical Trial * Randomized Controlled Trial MeSH Terms: * Adult * Double-Blind Method * Enzyme Inhibitors/therapeutic use* * Female * Humans * Male * Middle Aged * Nitric-Oxide Synthase/antagonists & inhibitors* * Pain Measurement * Research Support, Non-U.S. Gov't * Tension Headache/drug therapy* * omega-N-Methylarginine/therapeutic use* Substances: * Enzyme Inhibitors * omega-N-Methylarginine * Nitric-Oxide Synthase
作成者	飯塚高浩

18) Bove G, Nilsson N. Spinal manipulation in the treatment of episodic 　 tension-type headache: a randomized controlled trial. JAMA. 1998 　 Nov 11;280(18):1576-9.
論文抄録	CONTEXT: Episodic tension-type headache is common and is often treated using manual therapies. Few data exist for the efficacy of these interventions. OBJECTIVE: To determine the effects of spinal manipulation therapy on adults with episodic tension-type headache. DESIGN: Randomized controlled trial lasting 19 weeks. SETTING: Outpatient facility of a National Health Service-funded chiropractic research institution in Denmark . PARTICIPANTS: Volunteer sample of 26 men and 49 women aged 20 to 59 years who met the diagnostic criteria for episodic tension-type headache as defined by the International Headache Society. INTERVENTION: Participants were randomized into 2 groups, 1 receiving soft tissue therapy and spinal manipulation (the manipulation group), and the other receiving soft tissue therapy and a placebo laser treatment (the control group). All participants received 8 treatments over 4 weeks; all treatments were performed by the same chiropractor. MAIN OUTCOME MEASURES: Daily hours of headache, pain intensity per episode, and daily analgesic use, as recorded in diaries. RESULTS: Based on intent-to-treat analysis, no significant differences between the manipulation and control groups were observed in any of the 3 outcome measures. However, by week 7, each group experienced significant reductions in mean daily headache hours (manipulation group, reduction from 2.8 to 1.5 hours; control group, reduction from 3.4 to 1.9 hours) and mean number of analgesics per day (manipulation group, reduction from 0.66 to 0.38; control group, reduction from 0.82 to 0.59). These changes were maintained through the observation period. Headache pain intensity was unchanged for the duration of the trial. CONCLUSION: As an isolated intervention, spinal manipulation does not seem to have a positive effect on episodic tension-type headache.
文献 PubMed − ID	PMID:9820258
エビデンスレベル	Ib
文献タイトル ( 日本語 )	発作性緊張型頭痛 (ETTH) における指圧効果：無作為対照試験
目的	ETTH における脊椎指圧の有効性を検証すること
研究デザイン	無作為プラセボ対照試験（ Randomized, placebo-controlled study ）
研究施設	National Health Service-funded chiropractic research institution in Denmark
研究期間	N/A
対象患者	75 人の ETTH 患者（月に 5 回以上 15 回以下， 0 から 100 の visual analogue scale で頭痛強度が 25 から 85 の間にある ETTH ）
介入	指圧師によるマッサージと上部頚髄指圧を受ける指圧治療群とマッサージと低出力レザー光線照射をうける対照群の 2 群にわけて検討した． 4 週間にわたり合計 8 回の治療を行い，治療前後で 19 週にわたる臨床試験である．
主要評価項目とそれに用いた統計学的手法	主要項目は，１日あたりの頭痛持続時間，発作毎の平均頭痛強度，日々の鎮痛剤使用回数である． ITT 解析を行った，
結果	指圧群と対照群の間には有意差はなかった．
結論	指圧自体に，単独治療として ETTH の有効性があるとは言い難い．
備考	Publication Types: * Clinical Trial * Randomized Controlled Trial MeSH Terms: * Adult * Female * Humans * Male * Manipulation, Spinal* * Middle Aged * Research Support, Non-U.S. Gov't * Tension Headache/therapy* * Treatment Outcome
作成者	飯塚高浩