Антиконвульсанты для предупреждения мигренозных приступов

[Merab Lomia]

Уважаемые коллеги,
Используете ли вы вальпроаты и другие антиконвульсанты (топирамат, карбамазепин) для предупреждения частых мигренозных приступов?
Немаловажно, что в сравнении с триптанами, цены более приемлемы, да и публикаций в последнее время - много, особенно по вальпроатам.

[ErickRed]

Сообщение от Merab Lomia

Уважаемые коллеги,
Используете ли вы вальпроаты и другие антиконвульсанты (топирамат, карбамазепин) для предупреждения частых мигренозных приступов?
Немаловажно, что в сравнении с триптанами, цены более приемлемы, да и публикаций в последнее время - много, особенно по вальпроатам.

АЭП используются при неэффективности/противопоказанности других профилактических средств (бета-блокаторов, антагонистов кальция, антидепрессантов) при высокой частоте приступов.
С триптанами сравнивать нельзя, т.к. последние не используются для профилактики приступов мигрени, а для купирования оных.

[Baul]

Сообщение от ErickRed

С триптанами сравнивать нельзя, т.к. последние не используются для профилактики приступов мигрени, а для купирования оных.

Точно. Поэтому из-за эпизодичности применения триптаны не являются такой уж дорогой стороной расходов. А употребление триптанов при очень частых приступах вообще не рекомендуется.

Простит меня автор темы, если я в свою очередь задам сходный вопрос:
Не встречал ли кто публикаций и не имеет ли личного опыта лечения менструальной мигрени оральными контрацептивами. А то многие уважаемые неврологи, в том числе профессора, смотрят на меня диковато, когда я задаю им этот вопрос. Между тем я сталкивался с одной зарубежной статьей года 4 назад в одном из журналов. Там методика с результатами была. Только вот убейте не помню где.

[Light]

Может быть эта статья? -

"J Fam Plann Reprod Health Care. 2002 Jan;28(1):27-31
Prevention of migraine in the pill-free interval of combined oral contraceptives: a double-blind, placebo-controlled pilot study using natural oestrogen supplements.
Macgregor EA, Hackshaw A.
The City of London Migraine Clinic, London, UK.

CONTEXT: Migraine in the pill-free interval of combined oral contraceptives is reported by many women, but there is little published information on possible mechanisms and treatments. OBJECTIVE: To determine whether the use of natural oestrogen patches affected the occurrence and severity of migraine during the pill-free interval. DESIGN: A double-blind, placebo-controlled, randomised, crossover study. SETTING: The City of London Migraine Clinic. PARTICIPANTS: Fourteen women with migraine during the pill-free interval. INTERVENTIONS: 50 microg oestradiol patches (Evorel) used during the pill-free interval for two cycles versus placebo for two cycles (total four cycles). MAIN OUTCOME MEASURES: Number of pill-free intervals (zero, one or two) during which migraine occurred; number of days of migraine; severity of migraine; number of days of migraine accompanied by nausea, vomiting and/or photophobia. RESULTS: Complete data were available for 12 women and for two cycles for one woman. Use of 50 microg oestrogen patches during the pill-free interval showed a trend towards reducing the frequency and severity of migraine. DISCUSSION: These results were not as good as expected. However, we had originally aimed for 20 eligible women to participate in the trial, but only 14 were recruited and only 12 completed the study with full data for analysis. CONCLUSION: The results of this pilot study suggest that use of 50 microg oestrogen patches during the pill-free interval may reduce the frequency and severity of migraine at that time. This study should be repeated with larger numbers of women and a higher dose of oestrogen."
или эта -
"South Med J. 2004 Sep;97(9):819-22.
A novel specific prophylaxis for menstrual-associated migraine.
Calhoun AH.
Department of Neurology, University Headache Clinic, University of North Carolina at Chapel Hill, 3114 Bioinformatics Bldg., Campus Box 7025, Chapel Hill, NC 27599-7025, USA.

OBJECTIVES: Few migraine prophylactic therapies have demonstrated a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can discourage widespread usage. This article presents a pilot study of a novel, effective, specific, and inexpensive prophylactic strategy for menstrual-associated migraine. MATERIALS AND METHODS: Eleven women with menstrual-associated migraine and fewer than 14 days of headache per month were identified from prospective enrollment at a gynecology practice and retrospective chart review at a headache center. Exclusion criteria included current use of prophylactic therapy for migraine. METHODS: Patients received open-label therapy with an oral contraceptive containing 20 microg ethinyl estradiol on days 1 to 21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28. Headache intensity and bleeding were recorded in diaries that plotted headache days by oral contraceptive pill days. RESULTS: All of the patients achieved at least a 50% reduction in number of headache days per cycle (mean 77.9% reduction); 10 of the 11 women achieved at least a 50% reduction in weighted headache score (mean 76.3% reduction). CONCLUSIONS: All currently available estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl estradiol concentration equal to or greater than 20 microg. Estrogen supplementation during the placebo week can reduce the magnitude of this fall to less than 20 microg. When the decline is limited to the equivalent of 10 microg ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost of six dollars per headache-day prevented, this represents an effective and inexpensive strategy for a common migraine trigger."

[Merab Lomia]

Иногда вальпроаты даже для купирования длительного приступа полезны. Естественно, когда другие средства не помогают, а триптаны пациент купить не может. Было в практике несколько случаев. Правда, публикаций по купированию - не встречал.

[Mikhail]

Видел в аптеке, в Москве появились дженерики суматриптана. Есть российский за 400р/2 таб, и индийский, за 200. Но у последнего даже коробочка вся пожухлая... И фирму такую я первый раз видел. Короче, нет ощущения качества. Хотя, как известно, это не показатель.
Еще появился в продаже Элетриптан (Релпакс).

[Baul]

to Light

спасибо, хотя это и не те статьи.
to Mikhail
Элетриптан, кстати, широко исследовали в России, причем как раз в основном при менструальной мигрени. Говорят, что было довольно эффективно. Про доказательность судить не берусь.

[riltsov]

Сообщение от Baul

Не встречал ли кто публикаций и не имеет ли личного опыта лечения менструальной мигрени оральными контрацептивами. А то многие уважаемые неврологи, в том числе профессора, смотрят на меня диковато, когда я задаю им этот вопрос. Между тем я сталкивался с одной зарубежной статьей года 4 назад в одном из журналов. Там методика с результатами была. Только вот убейте не помню где.

Special Considerations in the Treatment of Migraine in Women
Semin Neurol 2006; 26: 217-222
Christine L. Lay1, Susan W. Broner
The Headache Institute, St. Luke's-Roosevelt Hospital Center, New York, New

ORAL CONTRACEPTIVE USE
For millions of women, oral contraceptive pills are the birth control method of choice; however, their use in migraineurs requires careful thought as their effect is unpredictable. When a woman with migraine begins oral contraceptive therapy, the migraine may improve, worsen, remain stable, or occur for the first time.[31] In women who experience a worsening of their migraines, it is typically during the placebo week. Generally speaking, oral contraceptive use is considered safe in women who experience migraine without aura or migraine with typical aura and in whom there is an absence of vascular risk factors.[32] If after beginning an oral contraceptive the aura pattern changes or develops for the first time, the oral contraceptive should be discontinued. As estrogen levels tend to fluctuate more with oral dosing, a patch or vaginal insert contraceptive may provide more steady-state levels and may be less likely to worsen migraine. When choosing an oral contraceptive it is best to choose a low dose, monophasic pill, rather than a mid- or high-dose pill. Biphasic and triphasic pills, although commonly prescribed, are generally not the best choice in migraineurs due to the fluctuating levels of estrogen. As previously noted, in women with menstrually related migraine, adding on estrogen during the placebo week can be helpful, as can noncycling of an oral contraceptive as it reduces the number of menstrual cycles and thus the number of menstrually related migraine.

EFNS guideline on the drug treatment of migraine – report of an EFNS task
force
Members of the task force: S. Evers, J. A´ fra, A. Frese, P. J. Goadsby, M. Linde, A. May and P. S. Sandor
European Journal of Neurology 2006, 13: 560–572

"Another prophylactic treatment regime of menstrual migraine is estrogen replacement therapy. The best evidence, although not as effective as betablockers or other first line prophylactic drugs, has been achieved for transdermal estradiol (not <100 lg given for 6 days perimenstrually as a gel or a patch) [157–160]."

[riltsov]

Hormonal Interventions for Menstrual Migraines
Kathleen J. Chavanu, Pharm.D., and Dannielle C. O’Donnell, Pharm.D.
Pharmacotherapy 2002;22(11):1442–1457

Hormone-Related Therapies For Menstrual
Migraines
Oral Contraceptives
Despite the controversy concerning the therapeutic role of oral contraceptives and the various effects of these agents on migraines and migraineurs, some women may improve with this therapy.26–28 In keeping with the theory that estrogen withdrawal and fluctuations in estrogen levels during the luteal phase are the major contributing factors to menstrual migraines, maintaining a low level of estrogen for an extended duration of time may alleviate or improve menstrual migraines. Studies have addressed the acceptance of extended-duration oral contraception use in women and the need for regimens that delay the pill-free week.15–19
An open-label, randomized, crossover study investigated the effect of oral contraceptives on migraine headaches.15 The study involved 40 women with histories of moderate or severe migraine with associated nausea, vomiting, photophobia, sensory symptoms, or a combination of these symptoms, which usually are not related to true menstrual migraine. Twenty patients were randomized to receive an oral contraceptive for 2 months, whereas the second group of 20 patients did not receive hormonal treatment. After 2 months, the second group received hormonal treatment and the first group received no hormonal treatment. Hormonal treatment consisted of a monophasiccombination oral contraceptive pill (norgestrel 0.5 mg–ethinyl estradiol 0.05 mg [Ovral]). Patients kept a self-rating card to record the number and severity of headaches, and the amount, kind, and success of therapy for each attack.
The results showed an increased frequency of moderate and severe headaches during the 2 months in which patients received oral contraceptives.15 Frequency of mild headaches also increased, but to a lesser extent than moderate and severe headaches. Twelve of the 40 patients reported improvement of their headaches while taking the oral contraceptive. Twenty-eight patients reported worsening of their headaches while receiving therapy. This study identified three distinct groups of patients: those with migraine headaches aggravated by oral contraceptives, those whose migraines decreased in severity or frequency when taking oral contraceptives, and those whose migraines were unaffected by oral contraceptives.
Another study, which involved 262 women receiving oral contraceptives, focused on hormone withdrawal symptoms, including menstrual migraines, over a 9-month period.16 Three groups of participants were recognized: 26 women who previously had not taken oral contraceptives, 43 women who had taken oral contraceptives but had not done so during the past 3 months, and 193 women who had been taking oral contraceptives for at least the past 12 months. Participants recorded their symptoms in daily diaries. All women were started or maintained on a combination low-dose oral contraceptive. This consisted of 21 active pills containing ethinyl estradiol 35 μg or less plus a progestin, and seven hormone-free pills. The women involved in the study were similar in age, height, weight, body mass index, race, and education. Participants were primarily Caucasian (84%) with high school education or greater (97%). The most common reasons for taking oral contraceptives were birth control and menstrual disorders. Outcomes investigated were headaches, pelvic pain, consumption of drugs for pain, menstrual flow, and symptoms such as nausea, vomiting, bloating, swelling, and breast tenderness. Patients subjectively scored their headaches on a scale of 0–10 (0 = no headache at all; 10 = worst headache). Headache data were split into two measures for analysis: any headache (pain score 1–10), and moderateto- severe headache (pain score 5–10).
Women who had been taking oral contraceptives before the start of the study complained of more symptoms during the pill-free interval than during the active-pill interval.16 Among this group significant differences emerged with regard to pelvic pain (70% vs 21%, p<0.001), headaches (70% vs 53%, p<0.001), consumption of drugs for pain (69% vs 43%, p<0.001), bloating or swelling (58% vs 19%, p<0.001), and breast tenderness (38% vs 16%, p<0.001) for the pillfree interval compared with the active-pill interval. The women who previously had not taken oral contraceptives experienced an increased number of headaches during the hormone-free interval of the second monitored cycle. During cycle 1, 62% of these women experienced headaches during the 3 active-pill weeks, compared with 71% during the hormonefree week (p=0.93). In cycle 2, the respective percentages were 49% and 71% (p<0.001), and in cycle 3, 51% and 60% (p=0.13).
Among women who had been taking oral contraceptives before the start of the study, the number of headaches increased during all hormone-free intervals.16 In cycle 1, 53% experienced any headache during the 3 active hormone weeks compared with 70% during the hormone-free week (p<0.01). In cycle 2, 45% experienced any headache during the 3 active hormone weeks, compared with 62% during the hormone-free week (p<0.01). As for the other outcomes, increased symptomatology occurred during the hormone-free interval. These data support the hypothesis of estrogen withdrawal and the association between the fall of estrogen and exacerbation of headaches.

[Dr.Vad]

Сообщение от Merab Lomia

Иногда вальпроаты даже для купирования длительного приступа полезны. Правда, публикаций по купированию - не встречал.

Вот кое что:

Tan V, Sahami AR, Peebles R, Shaw RJ.
Abdominal migraine and treatment with intravenous valproic acid.
Psychosomatics. 2006 Jul-Aug;47(4):353-5.

Tanen DA, Miller S, French T, Riffenburgh RH.
Intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headaches: a prospective, randomized, double-blind trial.
Ann Emerg Med. 2003 Jun;41(6):847-53.

Norton J.
Use of intravenous valproate sodium in status migraine.
Headache. 2000 Oct;40(9):755-7

Freitag FG.
Divalproex in the treatment of migraine.
Psychopharmacol Bull. 2003;37 Suppl 2:98-115.
Valproic acid in its various formulations has been demonstrated to be an efficacious and well-tolerated agent for the preventive treatment of migraine, chronic daily headache, and cluster headache. Additionally, it has been demonstrated to be efficacious and well tolerated in treating acute migraine attacks when given as an intravenous solution.

Edwards KR, Norton J, Behnke M.
Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache.
Headache. 2001 Nov-Dec;41(10):976-80.

Reiter PD, Nickisch J, Merritt G.
Efficacy and tolerability of intravenous valproic acid in acute adolescent migraine.
Headache. 2005 Jul-Aug;45(7):899-903.

Mathew NT, Kailasam J, Meadors L, Chernyschev O, Gentry P.
Intravenous valproate sodium (depacon) aborts migraine rapidly: a preliminary report.
Headache. 2000 Oct;40(9):720-3.

[Mikhail]

Сообщение от Baul

Элетриптан, кстати, широко исследовали в России, причем как раз в основном при менструальной мигрени. Говорят, что было довольно эффективно.

Честно говоря не видел работ, сравнивающих триптаны между собой. Вероятнее всего их эффективность примерно одинакова. Ну а выискивать конкурентные преимущества - задача маркетингового отдела

[webzee]

их можно рейтинговать по риску, а не по эффективности

[17q112]

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Противоэпилептические ср-ва безусловно находят свое применение в профилактике мигренозных пароксизмов. Сам я неоднократно рекомендовал пациентам их применение при наличии противопоказаний к назначению бета-блокаторов, или нежелании пациентов обращаться к помощи антидепресантов, использовал в основном депакин 500мг, вроде есть эффект.