㈿-5 AF

The efficacy, safety, and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache were investigated in a multicenter study over a period of up to 1 year. A total of 2,031 attacks were evaluated in 52 patients. Therapy was successful in 88% of all attacks. Freedom from pain within 15 minutes in more than 90% of all attacks treated was reported by 42% of the patients, and no decline in efficacy occurred during the course of the study. Adverse events were reported by 62% of the patients.

[Article in German]
The aim of the open prospective study was to investigate the efficacy, safety and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache. Self-treatment with 6 mg sumatriptan subcutaneously was monitored over a period up to 1 year. Headache parameters were documented by the patients with a headache diary. A total of 2031 attacks in 52 patients were investigated. Treatment with sumatriptan was effective in 88% of the attacks and 57% of the patients were pain-free within 15 min after injection; 42% of the patients became painfree within 15 min after at least 90% of their attacks. During long-time treatment the efficacy remained unchanged. Of the patients 10% withdrew from the study due to lack of efficacy or adverse events. In total, 62% of the patients reported adverse events, which were serious in 3.8% of the cases. Subcutaneous self-treatment of cluster headache is both highly effective and well tolerated.

PMID: 9748059
PMID: 9606683[Article in German]

群発頭痛急性期におけるスマトリプタンの効果 .1年間の長期研究．

スマトリプタン皮下注射の群発頭痛急性期に対する有効性，安全性，認容性を検討する．

Klinik fur Neurologie der Christian-Albrechts-Universitat Kiel, Germany
Neurologisch-verhaltensmedizinische Schmerzklinik Kiel in Kooperation mit dem Klinikum, Christian-Albrechts-Universitat Kiel.

52 人の群発頭痛患者．計 2031 回の発作．

注射後 15 分以内に頭痛が軽減したか．

皮下注射は 88% に有効でうち 57% は 15 分以内に症状が完全に鎮静した．長期間で有効性は変わらなかった．
痛みが 15 分以内にすべての 90% 以上抑えられた
10% の患者が効果なしまたは，副作用で脱落した．
62% がなんらかの副作用を感じたが，重症なものは 3.8% だった．

中規模の非盲検試験．

Publication Types:
・ Clinical Trial
･ Multicenter Study

MeSH Terms:
・Adult
・Cluster Headache/drug therapy*
・Female
・Human
・Injections, Subcutaneous
・Male
・Middle Aged
・Pain/drug therapy
・Prospective Studies
・Sumatriptan/administration & dosage
・Sumatriptan/adverse effects
・Sumatriptan/therapeutic use*
・Treatment Outcome

Substances:
・Sumatriptan

清水利彦，鈴木則宏

非盲検試験（ open study ）

Department of Neurology, Soder Hospital , Stockholm , Sweden

138 人の群発頭痛患者．計 6353 回の発作．

中規模の非盲検試験．

清水利彦，鈴木則宏

This multicentre, double-blind, randomised, crossover study compared the efficacy, safety and tolerability of subcutaneous sumatriptan (6 mg and 12 mg) with placebo in 134 in-patients with cluster headache. Headache improvement to mild or no pain at 5, 10 and 15 min after treatment was recorded. At 10 min, headache relief was reported by 25% (placebo), 49% (6 mg) and 63% (12 mg) of patients and at 15 min the results were 35% (placebo), 75% (6 mg) and 80% (12 mg) (p < 0.001 for all comparisons with placebo). The 12 mg dose was not significantly better than the 6 mg dose and was associated with more adverse events. The 6 mg dose is therefore recommended for the acute treatment of cluster headache.

群発頭痛急性期におけるスマトリプタン皮下注射：量比較試験．スマトリプタンと群発頭痛研究班．

群発頭痛急性期に対するスマトリプタン皮下注射 6 mg と 12mg の有効性，安全性を検討する．

無作為二重盲検プラセボ対照交差試験
（ multicentre, double-blind, randomised, crossover study ）

Department of Neurology, Soder Hospital , Stockholm , Sweden

13 ４人の群発頭痛患者．

頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分けた．治療の 5 分， 10 分， 15 分での頭痛の非常に重症，重症，中等度から軽度またはなしへの改善を記録．

10 分後，頭痛は placebo で 25% ，スマトリプタン 6mg で 49% ，スマトリプタン 12mg で 63% 改善， 15 分後は placebo で 35% ，スマトリプタン 6mg で 75% ，スマトリプタン 12mg で 80% 改善した ( 全ての群で placebo と比較し p < 0.001 ) ．スマトリプタン 12mg とスマトリプタン 6mg で有意な差はなく，副作用は増加した．

中規模の無作為二重盲検プラセボ対照交差試験．

Publication Types:
・Clinical Trial
・Multicenter Study
・Randomized Controlled Trial

MeSH Terms:
・Adolescent
・Adult
・Aged
・Cluster Headache/drug therapy*
・Comparative Study
・Cross-Sectional Studies
・Dose-Response Relationship, Drug
・Double-Blind Method
・Drug Tolerance
・Female
・Human
・Indoles/administration & dosage*
・Indoles/therapeutic use
・Injections, Subcutaneous
・Male
・Middle Aged
・Oxygen Inhalation Therapy
・Placebos
・Sulfonamides/administration & dosage*
・Sulfonamides/therapeutic use
・Sumatriptan
・Treatment Outcome
・Vasoconstrictor Agents/administration & dosage
・Vasoconstrictor Agents/therapeutic use

Substances:
・Indoles
・Placebos
・Sulfonamides
・Vasoconstrictor Agents
・Sumatriptan

清水利彦，鈴木則宏

BACKGROUND. Attacks of cluster headache are difficult to treat. Sumatriptan, an agonist of 5-hydroxytryptamine1-like receptors, has proved effective in the treatment of migraine. The clinical similarities between migraine and cluster headache and positive results from an open pilot study in patients with cluster headache indicated that sumatriptan should be evaluated more rigorously in the treatment of this condition. METHODS. We conducted a randomized, double-blind, placebo-controlled crossover study to assess the efficacy and tolerability of sumatriptan in 49 patients with cluster headache. The patients received, in random order, a subcutaneous injection of 6 mg of sumatriptan for one cluster-headache attack and placebo for another attack. The results for the two attacks could be fully evaluated for 39 patients. A response to treatment was defined as complete or almost complete relief of headache (no pain or mild pain) within 15 minutes after the injection. RESULTS. In the 39 patients, the severity of headache decreased in 74 percent of the attacks within 15 minutes of treatment with sumatriptan, as compared with 26 percent of the attacks for which placebo was given (P less than 0.001). Thirty-six percent of the patients were free of pain within 10 minutes after the administration of sumatriptan, as compared with 3 percent after placebo (P less than 0.001); by 15 minutes these numbers had increased to 46 percent and 10 percent, respectively (P less than 0.001). Thirteen percent of the patients required oxygen as an additional treatment 15 minutes after receiving sumatriptan, as compared with 49 percent of those who received placebo. The severity of functional disability and the incidence of ipsilateral conjunctival injection also decreased more in response to sumatriptan than placebo. Sumatriptan was well tolerated, and there were no serious adverse events. CONCLUSIONS. Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.

群発頭痛急性期におけるスマトリプタンの効果．スマトリプタン群発頭痛研究班

群発頭痛におけるスマトリプタンの効果と安全性を検討．

無作為二重盲検プラセボ対照交差試験
（ randomized, double-blind, placebo-controlled crossover study ）

3 ９人の群発頭痛患者．

15 分以内に頭痛が軽度またはなしに移行したら反応したと定義する．

３９例のうち１５分以内に頭痛軽減はスマトリプタン群で 74 ％， placebo 群で 26 ％に見られた（ p<0.001 ）． 10 分以内では頭痛消失はスマトリプタン群で 36 ％， placebo 群で 3 ％に見られ（ p<0.001 ）， 15 分後までにはスマトリプタン群で 46 ％， placebo 群で 10 ％に見られた（ p<0.001 ）．
15 分後に酸素を追加治療として必要とした症例はスマトリプタン群で 13 ％， placebo 群で 49 ％であった．機能障害の重症度と同側眼球結膜の充血はスマトリプタン投与群が placebo 投与群と比較しより減少させた．スマトリプタンは認容性にすぐれ重篤な副作用もなかった．
CONCLUSIONS. Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.

中規模の無作為二重盲検プラセボ対照交差試験．

清水利彦，鈴木則宏

SN-308( コハク酸スマトリプタン )3mg 注射液の群発頭痛に対する有効性及び安全性を比較検討するため , プラセボを対照とした二重盲検群間比較試験を実施した (Step 1). 同一群発期間における SN-308 3mg 注射液の反復投与群の有効性 , 安全性についても併せて検討した (Step 2)( 以下 ,Step 1 では SN-308 注射液を S 群 , プラセボ注射液を P 群 ,Step 2 では SN-308 注射液をスマトリプタンと表す ). 1) 登録症例は 40 例 , 内治験薬の投与症例は 34 例 (S 群 17 例 ,P 群 17 例 ), 未投与例が 6 例 .Step 2 へ移行した症例は 18 例 (S 群から 9 例 ,P 群から 9 例 ). 2) 有効性 . i)Step 1 投与後 30 分の頭痛改善度 ( 有効率 ) において ,S 群は P 群に比し有意に高い有効率を示す . ii)Step 2 本剤投与後 30 分の頭痛改善度 , 有効率は 75.3%(61/81 回 ) であった

SN-308(Sumatriptan) 皮下注射液の第 III 相臨床試験　群発頭痛患者を対象としたプラセボ注射液との二重盲検比較試験

群発頭痛におけるスマトリプタンの効果と安全性を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

3 ９人の群発頭痛患者．

中規模の無作為二重盲検プラセボ対照交差試験．

論文種類：原著論文 / ランダム化比較試験
シソーラス用語：プラセボ ; 頭痛 - 群発 ( 薬物療法 ); 皮下注射 ; 二重盲検法 ; ランダム化比較試験 ; Sumatriptan( 薬理学 , 治療的利用 ); 第 III 相試験
医中誌フリーキーワード：注射剤　チェックタグ：ヒト

清水利彦，鈴木則宏

BACKGROUND: Current evidence-based acute treatments of cluster headache are limited to oxygen inhalation and subcutaneous sumatriptan. Intranasal sumatriptan is a new formulation with better tolerability than the subcutaneous route. Two open-label studies suggested efficacy of intranasal sumatriptan in cluster headache. METHODS: In a double-blind placebo-controlled randomized trial, patients with episodic or chronic cluster headache whose attacks lasted at least 45 minutes each treated one attack with 20 mg sumatriptan nasal spray and another one, at least 24 hours later, with matching placebo. They scored their headache on a five-point scale (very severe, severe, moderate, mild, or none) at 5, 10, 15, 20, and 30 minutes. The primary outcome measure was headache response (a decrease in pain from very severe, severe, or moderate to mild or none) at 30 minutes. Secondary outcome measures included pain-free rates, relief of associated symptoms, and rates of adverse events. Multilevel multivariate analysis was used for statistical analysis. RESULTS: Five study centers enrolled 118 patients in whom 154 attacks were treated: 77 with sumatriptan and 77 with placebo. The responder rates at 30 minutes were 57% for sumatriptan and 26% for placebo (p = 0.002). Pain-free rates at 30 minutes were 47% for sumatriptan and 18% for placebo (p = 0.003). Sumatriptan was also superior to placebo considering initial response, meaningful relief, and relief of associated symptoms. There were no serious adverse events. CONCLUSION: Sumatriptan nasal spray is effective and well tolerated in the acute treatment of cluster headache attacks of at least 45 minutes' duration.

群発頭痛におけるスマトリプタン点鼻薬の効果：無作為二重盲検プラセボ対照比較試験

スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうか検討する．

無作為二重盲検プラセボ対照試験
（ Randomized, double-blind, placebo-controlled study ）

Department of Neurology, Leiden University Medical Centre, オランダ

反復性群発頭痛または慢性群発頭痛患者で発作が少なくとも 45 分持続する者 118 人で発作は 154 回，うち 77 回はスマトリプタン， 77 回は placebo で検査．

頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分け， 5 分， 10 分， 15 分， 20 分， 30 分に重症度を記載．第一の結果として， 30 分後に頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら responder とする．第 2 の結果として，頭痛消失者の割合，関連症候の軽減，副作用を調べる．

比較的うまくデザインされた中規模の RCT．

Publication Types:
• Clinical Trial
• Multicenter Study
• Randomized Controlled Trial
MeSH Terms:
• Administration, Intranasal
• Adult
• Cluster Headache/drug therapy*
• Cohort Studies
• Cross-Over Studies
• Double-Blind Method
• Female
• Human
• Male
• Serotonin Agonists/administration & dosage
• Serotonin Agonists/adverse effects
• Serotonin Agonists/therapeutic use*
• Sumatriptan/administration & dosage
• Sumatriptan/adverse effects
• Sumatriptan/therapeutic use*
• Support, Non-U.S. Gov't
• Time Factors
• Treatment Outcome
Substances:
• Serotonin Agonists
• Sumatriptan

清水利彦，鈴木則宏

We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was "pain free" 30 minutes after treatment. Secondary end-points included "headache response" (defined as headache improvement from "very severe", "severe" or moderate" pain to "mild" or "no" pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 "moderate" to "very severe" cluster headache attacks. 30 minutes after nasal spray application, 50% of attacks were completely aborted and 58% of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered "excellent" in two, "good" in four, "reasonable" in two and "poor" in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy.

群発頭痛急性期スマトリプタン点鼻薬 20mg による治療．非盲検試験

スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうか検討する．

非盲検試験（ open pilot study ）

Dept. of Neurology, Charite, Berlin , ドイツ

反復性群発頭痛または慢性群発頭痛患者 10 人．総発作回数は 154 回．

第 1 の結果として， 30 分後の頭痛消失の割合．第 2 の結果として，頭痛に対する反応を治療後 15 分， 30 分， 45 分， 60 分で見る．頭痛に対する反応は頭痛の程度を 5 段階（非常に重症，重症，中等度，軽度，なし）に分け，頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら反応ありと定義する．

小規模の非盲検試験．

Publication Types:
• Clinical Trial

MeSH Terms:
• Administration, Intranasal*
• Adult
• Cluster Headache/drug therapy*
• Cluster Headache/physiopathology
• Drug Tolerance
• Human
• Male
• Middle Aged
• Pain Measurement/drug effects
• Pilot Projects
• Serotonin Agonists/administration & dosage*
• Serotonin Agonists/adverse effects
• Sumatriptan/administration & dosage*
• Sumatriptan/adverse effects
• Support, Non-U.S. Gov't
• Treatment Outcome
• Variation (Genetics)

Substances:
• Serotonin Agonists
• Sumatriptan

清水利彦，鈴木則宏

Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers.

群発頭痛急性期におけるスマトリプタン点鼻薬 20mg の効果

スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうかを皮下注射と比較検討する．

無作為非盲検試験（ Randomized, open study ）

Department of Neurology, Lund University Hospital , Gothenburg , Sweden .

26 人の群発頭痛患者．

頭痛開始 5 分以内に治療を行い，頭痛開始から軽減までの時間， 15 分以内に頭痛軽減が起きたかを記録．有効性，副作用，治療の手間などを含めどちらがよいか患者に聞く．

皮下注射 52 例の治療で 49 例は 15 分以内に症状が完全に鎮静，平均時間は 9.6 分．残り 3 例の発作も 15 分の時点で平均 86.7% に減少．点鼻は 52 例の治療でわずか７例のみ有効．有効となる平均時間は 13 分．点鼻 18 例は 15 分で平均 42.2% 減少．のこり 27 例は効果をみとめなかった．頭痛側と反対に点鼻しても効果は同じであった． 26 人中 2 人が点鼻を好んだ．

中規模の無作為非盲検試験．

Publication Types:
• Clinical Trial
• Randomized Controlled Trial

MeSH Terms:
• Administration, Inhalation
• Adult
• Aged
• Cluster Headache/drug therapy*
• Dose-Response Relationship, Drug
• Female
• Human
• Injections, Subcutaneous
• Male
• Middle Aged
• Sumatriptan/therapeutic use*
• Vasoconstrictor Agents/therapeutic use*

Substances:
• Vasoconstrictor Agents
• Sumatriptan

清水利彦，鈴木則宏

OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache. METHODS: A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity was rated by a five-point scale: none, mild, moderate, severe, or very severe. Patients only treated moderate to very severe headaches. The primary efficacy measure was headache response (two-point or greater reduction from baseline in the cluster headache rating scale) at 30 minutes. Secondary efficacy measures included proportion of patients with initial headache relief within 15 and 30 minutes, mild or no pain at 30 minutes, meaningful headache relief, and use of escape medication. RESULTS: A total of 124 patients took at least one dose of study medication, with 73% having episodic and 27% chronic cluster headache. For the primary endpoint, there was a treatment-by-cluster-headache-type interaction (p = 0.0453). Therefore, results are presented separately for chronic and episodic cluster headache. In patients with episodic cluster headache, the difference between zolmitriptan 10 mg and placebo at 30 minutes reached significance (47% versus 29%; p = 0.02). Mild or no pain at 30 minutes was reported by 60%, 57%, and 42% patients treated with zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo (both p </= 0.01 versus placebo). For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints. In patients with chronic cluster headache, response rates following zolmitriptan 5 mg or 10 mg were not significantly different from placebo at any endpoint. Zolmitriptan 5 mg and 10 mg were well tolerated. CONCLUSION: Oral zolmitriptan is efficacious in episodic cluster headache.

群発頭痛急性期におけるゾルミトリプタン経口投与の有効性

群発頭痛急性期におけるゾルミトリプタン経口 5mg および 10mg 投与の有効性と認容性を評価する．

無作為二重盲検プラセボ対照交差試験
（ Randomized, double-blind, placebo-controlled crossover study ）

Institute of Neurology, Queen Square, London, イギリス

124 人の群発頭痛患者（反復性群発頭痛 73% ，慢性群発頭痛患者 27% ）．

頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分けた．非常に重症から中等度の頭痛発作を有する患者を対象とした．第１のエンドポイントして 30 分後に頭痛のスケールが 2 ポイント以上減少した場合を有効とした．第 2 のエンドポイントとして， 15 分と 30 分後の頭痛軽減者の割合， 30 分後に頭痛軽度またはなしの割合などとした．

反復性群発頭痛の患者では zolmitriptan 10 mg と placebo で 30 分後頭痛軽減の割合に有意差を認めた (47% versus 29%; p = 0.02). 30 分後に頭痛軽度またはなしの割合は zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo でそれぞれ 60%, 57%, and 42% h (10mg と 5mg でこ placebo と比較し p </= 0.01 ). 第 2 のエンドポイントでも zolmitriptan 10 mg と 5 mg は placebo に比較し有効性があった．
慢性群発頭痛の患者では zolmitriptan 5 mg o または 10 mg の投与は placebo と比較し効果がなかった．
Zolmitriptan 5 mg と 10 mg は認容性にすぐれていた．

中規模の無作為二重盲検プラセボ対照交差試験．

Publication Types:
• Clinical Trial
• Multicenter Study
• Randomized Controlled Trial

MeSH Terms:
• Acute Disease
• Administration, Oral
• Adult
• Aged
• Cluster Headache/drug therapy*
• Comparative Study
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Human
• Male
• Middle Aged
• Oxazoles/administration & dosage*
• Oxazoles/adverse effects
• Oxazolidinones*
• Pain Measurement
• Serotonin Agonists/administration & dosage*
• Serotonin Agonists/adverse effects
• Support, Non-U.S. Gov't
• Treatment Outcome

Substances:
• Oxazoles
• Oxazolidinones
• Serotonin Agonists
• zolmitriptan

清水利彦，鈴木則宏

Nineteen men, aged 20 to 50 years, were treated in a double-blind crossover study comparing oxygen v air inhalation at 6 L/min via nonrebreathing face masks for 15 minutes or less, for up to six headaches. Patients scored their own degree of relief for each treatment as none, slight, substantial, or complete relief. The average (+/- SE) relief score for all oxygen-treated patients was 1.93 +/- 0.22 out of a possible total score of 3.0, and for air the treatment relief score was 0.77 +/- 0.23. This difference is highly statistically significant by an analysis-of-variance F test; it documents that patients with cluster headache can benefit from oxygen inhalation during acute attacks.

群発頭痛の治療．酸素吸入と室内気吸入の二重盲検対照交差試験．

群発頭痛におけるスマトリプタンの効果と安全性を検討．

二重盲検プラセボ対照交差試験
（ double-blind, placebo-controlled crossover study ）

1 ９人の群発頭痛患者．

患者が頭痛の改善の程度を none （ほとんどなし） , slight （わずか） , substantial （かなり） , complete relief （完全）に分類．

酸素で治療した群では改善のスコアが 1.93 ± 0.22 ，空気で治療した例は 0.77 ± 0.23 と酸素で治療した場合が有意に高かった．

少規模の二重盲検プラセボ対照交差試験．

Publication Types:
・ Clinical Trial
・Controlled Clinical Trial

MeSH Terms:
・Adult
・Air
・Clinical Trials
・Cluster Headache/therapy*
・Double-Blind Method
・Human
・Male
・Middle Aged
・Oxygen/therapeutic use*
・Vascular Headaches/therapy*

Substances:
・Oxygen

清水利彦，鈴木則宏

Thirty male patients with cluster headache were given 4% lidocaine solution to use intranasally as an abortive therapy. Four sprays of lidocaine were used ipsilateral to the pain, and two more were used, if necessary. Twenty-seven percent of the men reported moderate relief, 27% obtained mild relief, and 46% stated that they had no relief from the lidocaine, Side effects were minimal. In this study, intranasal lidocaine was only a marginally helpful therapy for cluster headache. However, because of the ease of administration and lack of side effects, lidocaine may remain worthwhile as an adjunctive medication.

群発頭痛におけるリドカイン点鼻薬の効果．

Robbins Headache Clinic, Northbrook , Illinois , USA .

30 人の男性群発頭痛患者．

頭痛の改善度を中等度，軽度改善，改善なし，で評価．

27% は中等度改善， 27% は軽度改善， 46% は改善せず．副作用はほとんどなし．
リドカインは補助的な役割である．

中規模の無作為二重盲検プラセボ対照交差試験．

MeSH Terms:
• Administration, Intranasal
• Adult
• Cluster Headache/drug therapy*
• Human
• Lidocaine/adverse effects*
• Lidocaine/therapeutic use
• Male
• Middle Aged
• Treatment Outcome

Substances:
• Lidocaine

清水利彦，鈴木則宏

A double-blind trial of dihydroergotamine (DHE) nasal spray compared with placebo was carried out in patients with cluster headache. Twenty-five patients were included in the trial. In three patients, all receiving DHE, the pain attacks ceased after five attacks. In the other 22 patients, 133 attacks were treated with placebo and 137 attacks with DHE nasal spray (dosage, 1 mg of DHE). The trial showed that the treatment given has no effect on the attack frequency or the duration of the single attack. However, the treatment had a significant effect on the intensity of the single attacks. It can be concluded that the trial should be repeated, using a larger dosage of DHE. This should be ethically justifiable, since none of the patients had any adverse reactions locally in the mucous membrane of the nose or systemically.

群発頭痛発作に対するジヒドロエルゴタミン点鼻薬の役割．二重盲検プラセボ対照試験．

群発頭痛におけるジヒドロエルゴタミン点鼻薬の効果と安全性を検討．

無作為二重盲検プラセボ対照試験
（ randomized, double-blind, placebo-controlled study ）

25 人の群発頭痛患者．

この検討で，発作頻度または１回の発作の持続時間に変化はなし．しかし，１回の発作の重症度に効果あり．再検討が必要で，ジヒドロエルゴタミンの増量が必要である．副作用はなかった．

少規模の無作為二重盲検プラセボ対照試験．

Publication Types:
・Clinical Trial
・Controlled Clinical Trial

MeSH Terms:
・Administration, Intranasal
・Adult
・Clinical Trials
・Cluster Headache/drug therapy*
・Comparative Study
・Dihydroergotamine/administration & dosage
・Dihydroergotamine/therapeutic use*
・Double-Blind Method
・Female
・Human
・Male
・Middle Aged
・Time Factors
・Vascular Headaches/drug therapy*

Substances:
・Dihydroergotamine

清水利彦，鈴木則宏

The pain relieving effect of somatostatin treatment during 72 attacks of cluster headache in 8 male patients was compared to treatment with ergotamine or placebo in a double-blind study. Infusion of somatostatin (25 micrograms/min for 20 min i.v.) reduced the maximal pain intensity and the duration of pain significantly compared to placebo treatment, and to a degree comparable to ergotamine tartrate treatment (250 micrograms i.m.). The results obtained provide new information concerning the possible mechanism of cluster headache attacks and suggest a new therapeutic approach.

群発頭痛急性期にソマトスタチンは疼痛を軽減させる．

群発頭痛におけるソマトスタチンの効果を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

8 人の群発頭痛患者． 72 回の発作．

少規模の二重盲検プラセボ対照試験．

MeSH Terms:
・Adult
・Cluster Headache/drug therapy*
・Comparative Study
・Double-Blind Method
・Ergotamine
・Ergotamines/therapeutic use
・Human
・Infusions, Parenteral
・Male
・Middle Aged
・Somatostatin/therapeutic use*
・Support, Non-U.S. Gov't
・Vascular Headaches/drug therapy*

Substances:
・Ergotamines
・Ergotamine
・Somatostatin

清水利彦，鈴木則宏

Current practical evidence-based acute treatments of cluster headache are limited to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small randomized, double-blind trials suggested efficacy of somatostatin in cluster headache. We sought to determine whether octreotide, a somatostatin analog, is effective in the abortive treatment of acute cluster headache. Patients with episodic and chronic cluster headache, as defined by the International Headache Society, were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 24-hour break, using subcutaneous octreotide microg or matching placebo. The primary end point was the headache response defined as very severe, severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end point was examined using a multilevel analysis approach. A total of 57 patients were recruited of whom 46 provided efficacy data on attacks treated with octreotide and 45 with placebo. The headache response rate with subcutaneous octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment outcome as a binomial where response was determined by treatment, using the patient as the level 2 variable, and considering period effect, sex, and cluster headache type as other variables of interest, we found that the effect of subcutaneous octreotide 100 microg was significantly superior to placebo (p < 0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of cluster headache when compared with placebo. Nonvasconstrictor treatment of acute cluster headache is possible.

群発頭痛急性期に対する octreotide の皮下注射の効果．無作為二重盲検プラセボ対照交差試験

ソマトスタチンのアナログであるオクトレオチドの皮下注射が群発頭痛急性期に効果的かどうか検討する．

無作為二重盲検プラセボ対照交差試験
（ Randomized, double-blind, placebo-controlled crossover study ）

Headache Group, Institute of Neurology, Queen Square, London, イギリス

反復性群発頭痛または慢性群発頭痛患者 57 人．発作のうち 46 回はオクトレオチド， 45 回は placebo で検査．

エンドポイントとして， 30 分後頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら有効とした．

小規模の非盲検試験．非血管収縮物質による治療の有効性を示す．

清水利彦，鈴木則宏

1) Gobel H, Lindner V, Heinze A, Ribbat M, Deuschl G. Gobel H, 　 Lindner V, Pfaffenrath V, Ribbat M, Heinze A, Stolze Ｈ. 　 [Article in German] Acute therapy for cluster headache with 　 sumatriptan: findings of a one-year long-term study. 　 [Acute therapy of episodic and chronic cluster headache 　 with sumatriptan s.c. Results of a one-year long-term study] 　 [Article in German] Neurology. 1998 Sep;51(3):908-11. 　 Nervenarzt. 1998 Apr;69(4):320-9[Article in German]
論文抄録	The efficacy, safety, and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache were investigated in a multicenter study over a period of up to 1 year. A total of 2,031 attacks were evaluated in 52 patients. Therapy was successful in 88% of all attacks. Freedom from pain within 15 minutes in more than 90% of all attacks treated was reported by 42% of the patients, and no decline in efficacy occurred during the course of the study. Adverse events were reported by 62% of the patients. [Article in German] The aim of the open prospective study was to investigate the efficacy, safety and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache. Self-treatment with 6 mg sumatriptan subcutaneously was monitored over a period up to 1 year. Headache parameters were documented by the patients with a headache diary. A total of 2031 attacks in 52 patients were investigated. Treatment with sumatriptan was effective in 88% of the attacks and 57% of the patients were pain-free within 15 min after injection; 42% of the patients became painfree within 15 min after at least 90% of their attacks. During long-time treatment the efficacy remained unchanged. Of the patients 10% withdrew from the study due to lack of efficacy or adverse events. In total, 62% of the patients reported adverse events, which were serious in 3.8% of the cases. Subcutaneous self-treatment of cluster headache is both highly effective and well tolerated.
文献 PubMed−ID	PMID: 9748059 PMID: 9606683[Article in German]
エビデンスレベル	㈵ b
文献タイトル (日本語)	群発頭痛急性期におけるスマトリプタンの効果 .1年間の長期研究．
目的	スマトリプタン皮下注射の群発頭痛急性期に対する有効性，安全性，認容性を検討する．
研究デザイン	臨床試験
研究施設	Klinik fur Neurologie der Christian-Albrechts-Universitat Kiel, Germany Neurologisch-verhaltensmedizinische Schmerzklinik Kiel in Kooperation mit dem Klinikum, Christian-Albrechts-Universitat Kiel.
研究期間	不明
対象患者	52 人の群発頭痛患者．計 2031 回の発作．
介入	群発頭痛患者で発作時スマトリプタン 6 mg 皮下注射を行いその経過を 1 年間日記に記載．
主要評価項目とそれに用いた統計学的手法	注射後 15 分以内に頭痛が軽減したか．
結果	皮下注射は 88% に有効でうち 57% は 15 分以内に症状が完全に鎮静した．長期間で有効性は変わらなかった．痛みが 15 分以内にすべての 90% 以上抑えられた 10% の患者が効果なしまたは，副作用で脱落した． 62% がなんらかの副作用を感じたが，重症なものは 3.8% だった．
結論	スマトリプタン皮下注射は効果あり，安全である．
コメント -1	中規模の非盲検試験．
コメント -2	2002 年神経学会頭痛治療ガイドライン文献 5
備考	Publication Types: ・ Clinical Trial ･ Multicenter Study MeSH Terms: ・Adult ・Cluster Headache/drug therapy* ・Female ・Human ・Injections, Subcutaneous ・Male ・Middle Aged ・Pain/drug therapy ・Prospective Studies ・Sumatriptan/administration & dosage ・Sumatriptan/adverse effects ・Sumatriptan/therapeutic use* ・Treatment Outcome Substances: ・Sumatriptan
作成者	清水利彦，鈴木則宏

2) Ekbom K, Krabbe A, Micieli G, Prusinski A, Cole JA, Pilgrim AJ, 　 Noronha D, Micelli G [corrected to Micieli G.Cluster headache 　 attacks treated for up to three months with subcutaneous 　 sumatriptan (6 mg). Sumatriptan Cluster Headache Long-term 　 Study Group. Cephalalgia. 1995 Jun;15(3):230-6.
論文抄録	In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.
文献 PubMed−ID	PMID: 7553814
エビデンスレベル	㈼
文献タイトル (日本語)	群発頭痛急性期におけるスマトリプタン 6 ｍｇ皮下注射による 3 ヶ月間の効果 .スマトリプタンと群発頭痛長期研究班．
目的	群発頭痛急性期に対するスマトリプタン皮下注射の 1 年間の非盲検試験で最初の 1 ヶ月の有効性，安全性を検討する．
研究デザイン	非盲検試験（ open study ）
研究施設	Department of Neurology, Soder Hospital , Stockholm , Sweden
研究期間	不明
対象患者	138 人の群発頭痛患者．計 6353 回の発作．
介入	群発頭痛患者で発作時スマトリプタン 6 mg 皮下注射（最大 1 日 2 回まで）を行いその経過を 1 年間日記に記載．
主要評価項目とそれに用いた統計学的手法	頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分けた． 15 分以内に頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら responder とする．
結果	スマトリプタン使用した 28% に何らかの副作用があったが片頭痛患者で長期使用の際に見られたものと同じ内容であった．発生率はスマトリプタンの頻回使用例でも変わらなかった．バイタルサイン，心電図，血液検査に変化を認めなかった．頭痛の軽減は皮下注射の 96% に認められた．長期間によるタフィキラキシー，効果の現れる時間の延長，頭痛頻度の増加は認められなかった．
結論	スマトリプタン 6mg の皮下注射は長期使用しても効果あり，安全である．
コメント	中規模の非盲検試験．
備考	Publication Types: ・Clinical Trial ・Multicenter Study MeSH Terms: ・Adolescent ・Adul ・Aged ・Cluster Headache/drug therapy* ・Cluster Headache/physiopathology ・Female ・Human ・Injections, Subcutaneous ・Male ・Middle Aged ・Sumatriptan/administration & dosage ・Sumatriptan/adverse effects ・Sumatriptan/therapeutic use* ・Time Factors Substances: ・Sumatriptan
作成者	清水利彦，鈴木則宏

3) Ekbom K, Monstad I, Prusinski A, Cole JA, Pilgrim AJ, Noronha D. 　 Subcutaneous sumatriptan in the acute treatment of cluster 　 headache: a dose comparison study. The Sumatriptan Cluster 　 Headache Study Group.Acta Neurol Scand. 1993 Jul;88(1):63-9.
論文抄録	This multicentre, double-blind, randomised, crossover study compared the efficacy, safety and tolerability of subcutaneous sumatriptan (6 mg and 12 mg) with placebo in 134 in-patients with cluster headache. Headache improvement to mild or no pain at 5, 10 and 15 min after treatment was recorded. At 10 min, headache relief was reported by 25% (placebo), 49% (6 mg) and 63% (12 mg) of patients and at 15 min the results were 35% (placebo), 75% (6 mg) and 80% (12 mg) (p < 0.001 for all comparisons with placebo). The 12 mg dose was not significantly better than the 6 mg dose and was associated with more adverse events. The 6 mg dose is therefore recommended for the acute treatment of cluster headache.
文献 PubMed−ID	PMID: 8396833
エビデンスレベル	㈵ b
文献タイトル (日本語)	群発頭痛急性期におけるスマトリプタン皮下注射：量比較試験．スマトリプタンと群発頭痛研究班．
目的	群発頭痛急性期に対するスマトリプタン皮下注射 6 mg と 12mg の有効性，安全性を検討する．
研究デザイン	無作為二重盲検プラセボ対照交差試験（ multicentre, double-blind, randomised, crossover study ）
研究施設	Department of Neurology, Soder Hospital , Stockholm , Sweden
研究期間	不明
対象患者	13 ４人の群発頭痛患者．
介入	群発頭痛患者で発作時スマトリプタン 6 mg ， 12mg ， placebo 皮下注射を行う．
主要評価項目とそれに用いた統計学的手法	頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分けた．治療の 5 分， 10 分， 15 分での頭痛の非常に重症，重症，中等度から軽度またはなしへの改善を記録．
結果	10 分後，頭痛は placebo で 25% ，スマトリプタン 6mg で 49% ，スマトリプタン 12mg で 63% 改善， 15 分後は placebo で 35% ，スマトリプタン 6mg で 75% ，スマトリプタン 12mg で 80% 改善した ( 全ての群で placebo と比較し p < 0.001 ) ．スマトリプタン 12mg とスマトリプタン 6mg で有意な差はなく，副作用は増加した．
結論	群発頭痛に対してはスマトリプタン 6mg の皮下注射が薦められる．
コメント -1	中規模の無作為二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 3
備考	Publication Types: ・Clinical Trial ・Multicenter Study ・Randomized Controlled Trial MeSH Terms: ・Adolescent ・Adult ・Aged ・Cluster Headache/drug therapy* ・Comparative Study ・Cross-Sectional Studies ・Dose-Response Relationship, Drug ・Double-Blind Method ・Drug Tolerance ・Female ・Human ・Indoles/administration & dosage* ・Indoles/therapeutic use ・Injections, Subcutaneous ・Male ・Middle Aged ・Oxygen Inhalation Therapy ・Placebos ・Sulfonamides/administration & dosage* ・Sulfonamides/therapeutic use ・Sumatriptan ・Treatment Outcome ・Vasoconstrictor Agents/administration & dosage ・Vasoconstrictor Agents/therapeutic use Substances: ・Indoles ・Placebos ・Sulfonamides ・Vasoconstrictor Agents ・Sumatriptan
作成者	清水利彦，鈴木則宏

4) [No authors listed] Treatment of acute cluster headache with 　 sumatriptan. The Sumatriptan Cluster Headache Study Group. 　 N Engl J Med. 1991 Aug 1;325(5):322-6.
論文抄録	BACKGROUND. Attacks of cluster headache are difficult to treat. Sumatriptan, an agonist of 5-hydroxytryptamine1-like receptors, has proved effective in the treatment of migraine. The clinical similarities between migraine and cluster headache and positive results from an open pilot study in patients with cluster headache indicated that sumatriptan should be evaluated more rigorously in the treatment of this condition. METHODS. We conducted a randomized, double-blind, placebo-controlled crossover study to assess the efficacy and tolerability of sumatriptan in 49 patients with cluster headache. The patients received, in random order, a subcutaneous injection of 6 mg of sumatriptan for one cluster-headache attack and placebo for another attack. The results for the two attacks could be fully evaluated for 39 patients. A response to treatment was defined as complete or almost complete relief of headache (no pain or mild pain) within 15 minutes after the injection. RESULTS. In the 39 patients, the severity of headache decreased in 74 percent of the attacks within 15 minutes of treatment with sumatriptan, as compared with 26 percent of the attacks for which placebo was given (P less than 0.001). Thirty-six percent of the patients were free of pain within 10 minutes after the administration of sumatriptan, as compared with 3 percent after placebo (P less than 0.001); by 15 minutes these numbers had increased to 46 percent and 10 percent, respectively (P less than 0.001). Thirteen percent of the patients required oxygen as an additional treatment 15 minutes after receiving sumatriptan, as compared with 49 percent of those who received placebo. The severity of functional disability and the incidence of ipsilateral conjunctival injection also decreased more in response to sumatriptan than placebo. Sumatriptan was well tolerated, and there were no serious adverse events. CONCLUSIONS. Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.
文献 PubMed−ID	PMID: 1647496
エビデンスレベル	㈵ b
文献タイトル (日本語)	群発頭痛急性期におけるスマトリプタンの効果．スマトリプタン群発頭痛研究班
目的	群発頭痛におけるスマトリプタンの効果と安全性を検討．
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 ）
研究期間	不明
対象患者	3 ９人の群発頭痛患者．
介入	群発頭痛患者の発作にランダムに１回はスマトリプタン６ mg 皮下注射，もう一回は placebo を使う．
主要評価項目とそれに用いた統計学的手法	15 分以内に頭痛が軽度またはなしに移行したら反応したと定義する．
結果	３９例のうち１５分以内に頭痛軽減はスマトリプタン群で 74 ％， placebo 群で 26 ％に見られた（ p<0.001 ）． 10 分以内では頭痛消失はスマトリプタン群で 36 ％， placebo 群で 3 ％に見られ（ p<0.001 ）， 15 分後までにはスマトリプタン群で 46 ％， placebo 群で 10 ％に見られた（ p<0.001 ）． 15 分後に酸素を追加治療として必要とした症例はスマトリプタン群で 13 ％， placebo 群で 49 ％であった．機能障害の重症度と同側眼球結膜の充血はスマトリプタン投与群が placebo 投与群と比較しより減少させた．スマトリプタンは認容性にすぐれ重篤な副作用もなかった． CONCLUSIONS. Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.
結論	スマトリプタンは群発頭痛の急性期に有効で認容性にもすぐれている．
コメント -1	中規模の無作為二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献２
作成者	清水利彦，鈴木則宏

5) 坂井文彦 ( 北里大学医学部附属病院神経内科 ), 福内靖男 , 松本清 , 　宮崎東洋 , 中島健二 , 大橋和史 . 臨床医薬 (0910-8211)16 巻 3 号　 Page301-323(2000.03)
論文抄録	SN-308( コハク酸スマトリプタン )3mg 注射液の群発頭痛に対する有効性及び安全性を比較検討するため , プラセボを対照とした二重盲検群間比較試験を実施した (Step 1). 同一群発期間における SN-308 3mg 注射液の反復投与群の有効性 , 安全性についても併せて検討した (Step 2)( 以下 ,Step 1 では SN-308 注射液を S 群 , プラセボ注射液を P 群 ,Step 2 では SN-308 注射液をスマトリプタンと表す ). 1) 登録症例は 40 例 , 内治験薬の投与症例は 34 例 (S 群 17 例 ,P 群 17 例 ), 未投与例が 6 例 .Step 2 へ移行した症例は 18 例 (S 群から 9 例 ,P 群から 9 例 ). 2) 有効性 . i)Step 1 投与後 30 分の頭痛改善度 ( 有効率 ) において ,S 群は P 群に比し有意に高い有効率を示す . ii)Step 2 本剤投与後 30 分の頭痛改善度 , 有効率は 75.3%(61/81 回 ) であった
文献 PubMed−ID	2000176589
エビデンスレベル	㈵ b
文献タイトル (日本語)	SN-308(Sumatriptan) 皮下注射液の第 III 相臨床試験　群発頭痛患者を対象としたプラセボ注射液との二重盲検比較試験
目的	群発頭痛におけるスマトリプタンの効果と安全性を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究期間	不明
対象患者	3 ９人の群発頭痛患者．
介入	群発頭痛患者の発作にランダムに１回はスマトリプタン６ mg 皮下注射，もう一回は placebo を使う．
結果	SN-308( コハク酸スマトリプタン )3mg 注射液の群発頭痛に対する有効性及び安全性を比較検討するため , プラセボを対照とした二重盲検群間比較試験を実施した (Step 1). 同一群発期間における SN-308 3mg 注射液の反復投与群の有効性 , 安全性についても併せて検討した (Step 2)( 以下 ,Step 1 では SN-308 注射液を S 群 , プラセボ注射液を P 群 ,Step 2 では SN-308 注射液をスマトリプタンと表す ). 1) 登録症例は 40 例 , 内治験薬の投与症例は 34 例 (S 群 17 例 ,P 群 17 例 ), 未投与例が 6 例 .Step 2 へ移行した症例は 18 例 (S 群から 9 例 ,P 群から 9 例 ). 2) 有効性 . i)Step 1 投与後 30 分の頭痛改善度 ( 有効率 ) において ,S 群は P 群に比し有意に高い有効率を示す . ii)Step 2 本剤投与後 30 分の頭痛改善度 , 有効率は 75.3%(61/81 回 ) であった
結論	スマトリプタンは群発頭痛の急性期に有効で認容性にもすぐれている．
コメント -1	中規模の無作為二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 7
備考	論文種類：原著論文 / ランダム化比較試験シソーラス用語：プラセボ ; 頭痛 - 群発 ( 薬物療法 ); 皮下注射 ; 二重盲検法 ; ランダム化比較試験 ; Sumatriptan( 薬理学 , 治療的利用 ); 第 III 相試験医中誌フリーキーワード：注射剤　チェックタグ：ヒト
作成者	清水利彦，鈴木則宏

6) van Vliet JA, Bahra A, Martin V, Ramadan N, Aurora SK, Mathew NT, 　 Ferrari MD, Goadsby PJ. Intranasal sumatriptan in cluster headache: 　 randomized placebo-controlled double-blind study. Neurology. 　 2003 Feb 25;60(4):630-3.
論文抄録	BACKGROUND: Current evidence-based acute treatments of cluster headache are limited to oxygen inhalation and subcutaneous sumatriptan. Intranasal sumatriptan is a new formulation with better tolerability than the subcutaneous route. Two open-label studies suggested efficacy of intranasal sumatriptan in cluster headache. METHODS: In a double-blind placebo-controlled randomized trial, patients with episodic or chronic cluster headache whose attacks lasted at least 45 minutes each treated one attack with 20 mg sumatriptan nasal spray and another one, at least 24 hours later, with matching placebo. They scored their headache on a five-point scale (very severe, severe, moderate, mild, or none) at 5, 10, 15, 20, and 30 minutes. The primary outcome measure was headache response (a decrease in pain from very severe, severe, or moderate to mild or none) at 30 minutes. Secondary outcome measures included pain-free rates, relief of associated symptoms, and rates of adverse events. Multilevel multivariate analysis was used for statistical analysis. RESULTS: Five study centers enrolled 118 patients in whom 154 attacks were treated: 77 with sumatriptan and 77 with placebo. The responder rates at 30 minutes were 57% for sumatriptan and 26% for placebo (p = 0.002). Pain-free rates at 30 minutes were 47% for sumatriptan and 18% for placebo (p = 0.003). Sumatriptan was also superior to placebo considering initial response, meaningful relief, and relief of associated symptoms. There were no serious adverse events. CONCLUSION: Sumatriptan nasal spray is effective and well tolerated in the acute treatment of cluster headache attacks of at least 45 minutes' duration.
文献 PubMed−ID	PMID: 12601104
エビデンスレベル	㈵ b
文献タイトル (日本語)	群発頭痛におけるスマトリプタン点鼻薬の効果：無作為二重盲検プラセボ対照比較試験
目的	スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうか検討する．
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, Leiden University Medical Centre, オランダ
研究期間	不明
対象患者	反復性群発頭痛または慢性群発頭痛患者で発作が少なくとも 45 分持続する者 118 人で発作は 154 回，うち 77 回はスマトリプタン， 77 回は placebo で検査．
介入	初回発作を 20mg のスマトリプタン点鼻で治療，その後 24 時間以上空けて 2 回目の点鼻を施行． placebo 　と比較した．
主要評価項目とそれに用いた統計学的手法	頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分け， 5 分， 10 分， 15 分， 20 分， 30 分に重症度を記載．第一の結果として， 30 分後に頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら responder とする．第 2 の結果として，頭痛消失者の割合，関連症候の軽減，副作用を調べる．
結果	Responder は 30 分でスマトリプタン群が 57% で placebo で 26% だった (p = 0.002). Pain-free rates at 30 分後に頭痛消失した割合はスマトリプタン群で 47% ， placebo 群で 18% だった (p = 0.003). スマトリプタン群は関連する症状も placebo 群より改善させ，副作用はなかった．
結論	スマトリプタンの点鼻薬は急性期群発頭痛に有効である．
コメント	比較的うまくデザインされた中規模の RCT．
備考	Publication Types: • Clinical Trial • Multicenter Study • Randomized Controlled Trial MeSH Terms: • Administration, Intranasal • Adult • Cluster Headache/drug therapy* • Cohort Studies • Cross-Over Studies • Double-Blind Method • Female • Human • Male • Serotonin Agonists/administration & dosage • Serotonin Agonists/adverse effects • Serotonin Agonists/therapeutic use* • Sumatriptan/administration & dosage • Sumatriptan/adverse effects • Sumatriptan/therapeutic use* • Support, Non-U.S. Gov't • Time Factors • Treatment Outcome Substances: • Serotonin Agonists • Sumatriptan
作成者	清水利彦，鈴木則宏

7) Schuh-Hofer S, Reuter U, Kinze S, Einhaupl KM, Arnold G. 　 Treatment of acute cluster headache with 20 mg sumatriptan nasal 　 spray--an open pilot study. J Neurol. 2002 Jan;249(1):94-9.
論文抄録	We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was "pain free" 30 minutes after treatment. Secondary end-points included "headache response" (defined as headache improvement from "very severe", "severe" or moderate" pain to "mild" or "no" pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 "moderate" to "very severe" cluster headache attacks. 30 minutes after nasal spray application, 50% of attacks were completely aborted and 58% of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered "excellent" in two, "good" in four, "reasonable" in two and "poor" in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy.
文献 PubMed−ID	PMID: 11954875
エビデンスレベル	㈼
文献タイトル (日本語)	群発頭痛急性期スマトリプタン点鼻薬 20mg による治療．非盲検試験
目的	スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうか検討する．
研究デザイン	非盲検試験（ open pilot study ）
研究施設	Dept. of Neurology, Charite, Berlin , ドイツ
研究期間	不明
対象患者	反復性群発頭痛または慢性群発頭痛患者 10 人．総発作回数は 154 回．
介入	初回発作を 20mg のスマトリプタン点鼻で治療し効果を見た．
主要評価項目とそれに用いた統計学的手法	第 1 の結果として， 30 分後の頭痛消失の割合．第 2 の結果として，頭痛に対する反応を治療後 15 分， 30 分， 45 分， 60 分で見る．頭痛に対する反応は頭痛の程度を 5 段階（非常に重症，重症，中等度，軽度，なし）に分け，頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら反応ありと定義する．
結果	スマトリプタン点鼻薬投与 30 分後で群発頭痛発作の 50% は完全に消失し，発作の 58% はスマトリプタン点鼻薬に反応した． 10 人中 2 人はスマトリプタン点鼻薬を "excellent" ， 2 人は "good" ， 4 人は "reasonable" ， 2 人は "poor" と評価． 10 人中 8 人はその後もスマトリプタン点鼻薬を用いるつもりと答えた．半年後 10 人中 7 人にインタビューした．うち 4 人はスマトリプタン点鼻薬を用い， 2 人は皮下注， 1 人は発作消失した．
結論	スマトリプタン 20 mg 点鼻薬は群発頭痛に有効かもしれないが，二重盲検試験が必要である．
コメント	小規模の非盲検試験．
備考	Publication Types: • Clinical Trial MeSH Terms: • Administration, Intranasal* • Adult • Cluster Headache/drug therapy* • Cluster Headache/physiopathology • Drug Tolerance • Human • Male • Middle Aged • Pain Measurement/drug effects • Pilot Projects • Serotonin Agonists/administration & dosage* • Serotonin Agonists/adverse effects • Sumatriptan/administration & dosage* • Sumatriptan/adverse effects • Support, Non-U.S. Gov't • Treatment Outcome • Variation (Genetics) Substances: • Serotonin Agonists • Sumatriptan
作成者	清水利彦，鈴木則宏

8) Hardebo JE, Dahlof C. Sumatriptan nasal spray (20 mg/dose) in the 　 acute treatment of cluster headache.Cephalalgia. 　 1998 Sep;18(7):487-9.
論文抄録	Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers.
文献 PubMed−ID	PMID: 9793702
エビデンスレベル	㈵ c
文献タイトル (日本語)	群発頭痛急性期におけるスマトリプタン点鼻薬 20mg の効果
目的	スマトリプタン点鼻薬が群発頭痛急性期に効果的かどうかを皮下注射と比較検討する．
研究デザイン	無作為非盲検試験（ Randomized, open study ）
研究施設	Department of Neurology, Lund University Hospital , Gothenburg , Sweden .
研究期間	不明
対象患者	26 人の群発頭痛患者．
介入	群発頭痛患者で 4 回の連続した頭痛発作に対しスマトリプタン点鼻 (20 mg/dose) と皮下注射を交互の行う．
主要評価項目とそれに用いた統計学的手法	頭痛開始 5 分以内に治療を行い，頭痛開始から軽減までの時間， 15 分以内に頭痛軽減が起きたかを記録．有効性，副作用，治療の手間などを含めどちらがよいか患者に聞く．
結果	皮下注射 52 例の治療で 49 例は 15 分以内に症状が完全に鎮静，平均時間は 9.6 分．残り 3 例の発作も 15 分の時点で平均 86.7% に減少．点鼻は 52 例の治療でわずか７例のみ有効．有効となる平均時間は 13 分．点鼻 18 例は 15 分で平均 42.2% 減少．のこり 27 例は効果をみとめなかった．頭痛側と反対に点鼻しても効果は同じであった． 26 人中 2 人が点鼻を好んだ．
結論	スマトリプタン点鼻は皮下注射と比べると効果は少ない．
コメント -1	中規模の無作為非盲検試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 6
備考	Publication Types: • Clinical Trial • Randomized Controlled Trial MeSH Terms: • Administration, Inhalation • Adult • Aged • Cluster Headache/drug therapy* • Dose-Response Relationship, Drug • Female • Human • Injections, Subcutaneous • Male • Middle Aged • Sumatriptan/therapeutic use* • Vasoconstrictor Agents/therapeutic use* Substances: • Vasoconstrictor Agents • Sumatriptan
作成者	清水利彦，鈴木則宏

9) Bahra A, Gawel MJ, Hardebo JE, Millson D, Breen SA, Goadsby PJ. 　 Oral zolmitriptan is effective in the acute treatment of cluster 　 headache. Neurology. 2000 May 9;54(9):1832-9.
論文抄録	OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache. METHODS: A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity was rated by a five-point scale: none, mild, moderate, severe, or very severe. Patients only treated moderate to very severe headaches. The primary efficacy measure was headache response (two-point or greater reduction from baseline in the cluster headache rating scale) at 30 minutes. Secondary efficacy measures included proportion of patients with initial headache relief within 15 and 30 minutes, mild or no pain at 30 minutes, meaningful headache relief, and use of escape medication. RESULTS: A total of 124 patients took at least one dose of study medication, with 73% having episodic and 27% chronic cluster headache. For the primary endpoint, there was a treatment-by-cluster-headache-type interaction (p = 0.0453). Therefore, results are presented separately for chronic and episodic cluster headache. In patients with episodic cluster headache, the difference between zolmitriptan 10 mg and placebo at 30 minutes reached significance (47% versus 29%; p = 0.02). Mild or no pain at 30 minutes was reported by 60%, 57%, and 42% patients treated with zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo (both p </= 0.01 versus placebo). For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints. In patients with chronic cluster headache, response rates following zolmitriptan 5 mg or 10 mg were not significantly different from placebo at any endpoint. Zolmitriptan 5 mg and 10 mg were well tolerated. CONCLUSION: Oral zolmitriptan is efficacious in episodic cluster headache.
文献 PubMed−ID	PMID: 10802793
エビデンスレベル	㈼
文献タイトル (日本語)	群発頭痛急性期におけるゾルミトリプタン経口投与の有効性
目的	群発頭痛急性期におけるゾルミトリプタン経口 5mg および 10mg 投与の有効性と認容性を評価する．
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	Institute of Neurology, Queen Square, London, イギリス
研究期間	不明
対象患者	124 人の群発頭痛患者（反復性群発頭痛 73% ，慢性群発頭痛患者 27% ）．
介入	群発頭痛患者は， placebo ， zolmitriptan 5 mg および 10 mg をそれぞれ発作のたびに 1 錠ずつ経口摂取．
主要評価項目とそれに用いた統計学的手法	頭痛を 5 段階（非常に重症，重症，中等度，軽度，なし）のスケールに分けた．非常に重症から中等度の頭痛発作を有する患者を対象とした．第１のエンドポイントして 30 分後に頭痛のスケールが 2 ポイント以上減少した場合を有効とした．第 2 のエンドポイントとして， 15 分と 30 分後の頭痛軽減者の割合， 30 分後に頭痛軽度またはなしの割合などとした．
結果	反復性群発頭痛の患者では zolmitriptan 10 mg と placebo で 30 分後頭痛軽減の割合に有意差を認めた (47% versus 29%; p = 0.02). 30 分後に頭痛軽度またはなしの割合は zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo でそれぞれ 60%, 57%, and 42% h (10mg と 5mg でこ placebo と比較し p </= 0.01 ). 第 2 のエンドポイントでも zolmitriptan 10 mg と 5 mg は placebo に比較し有効性があった．慢性群発頭痛の患者では zolmitriptan 5 mg o または 10 mg の投与は placebo と比較し効果がなかった． Zolmitriptan 5 mg と 10 mg は認容性にすぐれていた．
結論	ゾルミトリプタン経口は反復性群発頭痛に有効．
コメント -1	中規模の無作為二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 8
備考	Publication Types: • Clinical Trial • Multicenter Study • Randomized Controlled Trial MeSH Terms: • Acute Disease • Administration, Oral • Adult • Aged • Cluster Headache/drug therapy* • Comparative Study • Cross-Over Studies • Dose-Response Relationship, Drug • Double-Blind Method • Female • Human • Male • Middle Aged • Oxazoles/administration & dosage* • Oxazoles/adverse effects • Oxazolidinones* • Pain Measurement • Serotonin Agonists/administration & dosage* • Serotonin Agonists/adverse effects • Support, Non-U.S. Gov't • Treatment Outcome Substances: • Oxazoles • Oxazolidinones • Serotonin Agonists • zolmitriptan
作成者	清水利彦，鈴木則宏

10) Fogan L.Treatment of cluster headache. 　 A double-blind comparison of oxygen v air inhalation . Arch Neurol. 　 1985 Apr;42(4):362-3.
論文抄録	Nineteen men, aged 20 to 50 years, were treated in a double-blind crossover study comparing oxygen v air inhalation at 6 L/min via nonrebreathing face masks for 15 minutes or less, for up to six headaches. Patients scored their own degree of relief for each treatment as none, slight, substantial, or complete relief. The average (+/- SE) relief score for all oxygen-treated patients was 1.93 +/- 0.22 out of a possible total score of 3.0, and for air the treatment relief score was 0.77 +/- 0.23. This difference is highly statistically significant by an analysis-of-variance F test; it documents that patients with cluster headache can benefit from oxygen inhalation during acute attacks.
文献 PubMed−ID	PMID: 3885921
エビデンスレベル	㈼
文献タイトル (日本語)	群発頭痛の治療．酸素吸入と室内気吸入の二重盲検対照交差試験．
目的	群発頭痛におけるスマトリプタンの効果と安全性を検討．
研究デザイン	二重盲検プラセボ対照交差試験（ double-blind, placebo-controlled crossover study ）
研究期間	不明
対象患者	1 ９人の群発頭痛患者．
介入	群発頭痛患者の発作に 15 分かん酸素または空気 6L/min を対照交差で吸入． 6 回の頭痛まで．
主要評価項目とそれに用いた統計学的手法	患者が頭痛の改善の程度を none （ほとんどなし） , slight （わずか） , substantial （かなり） , complete relief （完全）に分類．
結果	酸素で治療した群では改善のスコアが 1.93 ± 0.22 ，空気で治療した例は 0.77 ± 0.23 と酸素で治療した場合が有意に高かった．
結論	群発頭痛の急性期に酸素吸入は有効である．
コメント -1	少規模の二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 12
備考	Publication Types: ・ Clinical Trial ・Controlled Clinical Trial MeSH Terms: ・Adult ・Air ・Clinical Trials ・Cluster Headache/therapy* ・Double-Blind Method ・Human ・Male ・Middle Aged ・Oxygen/therapeutic use* ・Vascular Headaches/therapy* Substances: ・Oxygen
作成者	清水利彦，鈴木則宏

11) Robbins L. Intranasal lidocaine for cluster headache. Headache. 　 1995 Feb;35(2):83-4.
論文抄録	Thirty male patients with cluster headache were given 4% lidocaine solution to use intranasally as an abortive therapy. Four sprays of lidocaine were used ipsilateral to the pain, and two more were used, if necessary. Twenty-seven percent of the men reported moderate relief, 27% obtained mild relief, and 46% stated that they had no relief from the lidocaine, Side effects were minimal. In this study, intranasal lidocaine was only a marginally helpful therapy for cluster headache. However, because of the ease of administration and lack of side effects, lidocaine may remain worthwhile as an adjunctive medication.
文献 PubMed−ID	PMID: 7737866
エビデンスレベル	㈿
文献タイトル (日本語)	群発頭痛におけるリドカイン点鼻薬の効果．
目的	群発頭痛におけるリドカイン点鼻薬の効果．
研究デザイン	臨床試験
研究施設	Robbins Headache Clinic, Northbrook , Illinois , USA .
研究期間	不明
対象患者	30 人の男性群発頭痛患者．
介入	群発頭痛患者で発作時 4% リドカインの点鼻で頭痛の軽減を見る．
主要評価項目とそれに用いた統計学的手法	頭痛の改善度を中等度，軽度改善，改善なし，で評価．
結果	27% は中等度改善， 27% は軽度改善， 46% は改善せず．副作用はほとんどなし．リドカインは補助的な役割である．
結論	リドカインは副作用がないので試してみる価値のある治療である．
コメント -1	中規模の無作為二重盲検プラセボ対照交差試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 15
備考	MeSH Terms: • Administration, Intranasal • Adult • Cluster Headache/drug therapy* • Human • Lidocaine/adverse effects* • Lidocaine/therapeutic use • Male • Middle Aged • Treatment Outcome Substances: • Lidocaine
作成者	清水利彦，鈴木則宏

12) Andersson PG, Jespersen LT. Dihydroergotamine nasal spray in 　 the treatment of attacks of cluster headache. A double-blind trial 　 versus placebo. Cephalalgia. 1986 Mar;6(1):51-4.
論文抄録	A double-blind trial of dihydroergotamine (DHE) nasal spray compared with placebo was carried out in patients with cluster headache. Twenty-five patients were included in the trial. In three patients, all receiving DHE, the pain attacks ceased after five attacks. In the other 22 patients, 133 attacks were treated with placebo and 137 attacks with DHE nasal spray (dosage, 1 mg of DHE). The trial showed that the treatment given has no effect on the attack frequency or the duration of the single attack. However, the treatment had a significant effect on the intensity of the single attacks. It can be concluded that the trial should be repeated, using a larger dosage of DHE. This should be ethically justifiable, since none of the patients had any adverse reactions locally in the mucous membrane of the nose or systemically.
文献 PubMed−ID	PMID: 3516408
エビデンスレベル	㈿
文献タイトル (日本語)	群発頭痛発作に対するジヒドロエルゴタミン点鼻薬の役割．二重盲検プラセボ対照試験．
目的	群発頭痛におけるジヒドロエルゴタミン点鼻薬の効果と安全性を検討．
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 ）
研究期間	不明
対象患者	25 人の群発頭痛患者．
介入	3 人の群発頭痛患者はジヒドロエルゴタミン，２２人の群発頭痛患者は 133 回の発作は placebo ，１３７回の発作はジヒドロエルゴタミン点鼻（１ mg ）で治療．
結果	この検討で，発作頻度または１回の発作の持続時間に変化はなし．しかし，１回の発作の重症度に効果あり．再検討が必要で，ジヒドロエルゴタミンの増量が必要である．副作用はなかった．
結論	ジヒドロエルゴタミンの増量が必要である
コメント -1	少規模の無作為二重盲検プラセボ対照試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 17
備考	Publication Types: ・Clinical Trial ・Controlled Clinical Trial MeSH Terms: ・Administration, Intranasal ・Adult ・Clinical Trials ・Cluster Headache/drug therapy* ・Comparative Study ・Dihydroergotamine/administration & dosage ・Dihydroergotamine/therapeutic use* ・Double-Blind Method ・Female ・Human ・Male ・Middle Aged ・Time Factors ・Vascular Headaches/drug therapy* Substances: ・Dihydroergotamine
作成者	清水利彦，鈴木則宏

13) Sicuteri F, Geppetti P, Marabini S, Lembeck F. Pain relief by 　 somatostatin in attacks of cluster headache Pain. 　 1984 Apr;18(4):359-65.
論文抄録	The pain relieving effect of somatostatin treatment during 72 attacks of cluster headache in 8 male patients was compared to treatment with ergotamine or placebo in a double-blind study. Infusion of somatostatin (25 micrograms/min for 20 min i.v.) reduced the maximal pain intensity and the duration of pain significantly compared to placebo treatment, and to a degree comparable to ergotamine tartrate treatment (250 micrograms i.m.). The results obtained provide new information concerning the possible mechanism of cluster headache attacks and suggest a new therapeutic approach.
文献 PubMed−ID	PMID: 6145138
エビデンスレベル	㈵ b
文献タイトル (日本語)	群発頭痛急性期にソマトスタチンは疼痛を軽減させる．
目的	群発頭痛におけるソマトスタチンの効果を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究期間	不明
対象患者	8 人の群発頭痛患者． 72 回の発作．
介入	群発頭痛患者の発作にソマトスタチン 25ug/min を 20 分静注し，疼痛の強度と持続の変化を placebo または酒石酸エルゴタミン 250ug の筋注の程度と比較．
結論	結果は群発頭痛の考えうるメカニズムに新しい情報を提供し新しい治療に結びつく．
コメント	少規模の二重盲検プラセボ対照試験．
備考	MeSH Terms: ・Adult ・Cluster Headache/drug therapy* ・Comparative Study ・Double-Blind Method ・Ergotamine ・Ergotamines/therapeutic use ・Human ・Infusions, Parenteral ・Male ・Middle Aged ・Somatostatin/therapeutic use* ・Support, Non-U.S. Gov't ・Vascular Headaches/drug therapy* Substances: ・Ergotamines ・Ergotamine ・Somatostatin
作成者	清水利彦，鈴木則宏

14) Matharu MS, Levy MJ, Meeran K, Goadsby PJ. Subcutaneous 　 octreotide in cluster headache: randomized placebo-controlled 　 double-blind crossover study. Ann Neurol. 2004 Oct;56(4):488-94.
論文抄録	Current practical evidence-based acute treatments of cluster headache are limited to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small randomized, double-blind trials suggested efficacy of somatostatin in cluster headache. We sought to determine whether octreotide, a somatostatin analog, is effective in the abortive treatment of acute cluster headache. Patients with episodic and chronic cluster headache, as defined by the International Headache Society, were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 24-hour break, using subcutaneous octreotide microg or matching placebo. The primary end point was the headache response defined as very severe, severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end point was examined using a multilevel analysis approach. A total of 57 patients were recruited of whom 46 provided efficacy data on attacks treated with octreotide and 45 with placebo. The headache response rate with subcutaneous octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment outcome as a binomial where response was determined by treatment, using the patient as the level 2 variable, and considering period effect, sex, and cluster headache type as other variables of interest, we found that the effect of subcutaneous octreotide 100 microg was significantly superior to placebo (p < 0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of cluster headache when compared with placebo. Nonvasconstrictor treatment of acute cluster headache is possible.
文献 PubMed−ID	PMID: 15455406
エビデンスレベル	㈽
文献タイトル (日本語)	群発頭痛急性期に対する octreotide の皮下注射の効果．無作為二重盲検プラセボ対照交差試験
目的	ソマトスタチンのアナログであるオクトレオチドの皮下注射が群発頭痛急性期に効果的かどうか検討する．
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	Headache Group, Institute of Neurology, Queen Square, London, イギリス
研究期間	不明
対象患者	反復性群発頭痛または慢性群発頭痛患者 57 人．発作のうち 46 回はオクトレオチド， 45 回は placebo で検査．
介入	中等度以上の群発頭痛の発作， 24 時間以上の間隔を開けてオクトレオチド１００ m g または placebo で検査．
主要評価項目とそれに用いた統計学的手法	エンドポイントとして， 30 分後頭痛が非常に重症，重症，中等度から軽度またはなしに移行したら有効とした．
結果	オクトレオチド１００ m g 投与で 52% は有効， placebo で 36% 有効 (p < 0.01).
結論	オクトレオチド１００ m g は群発頭痛に有効．
コメント	小規模の非盲検試験．非血管収縮物質による治療の有効性を示す．
作成者	清水利彦，鈴木則宏