Tolerability and efficacy of almotriptan in the long-term treatment of migraine.

BACKGROUND: Almotriptan is a highly specific 5-HT(1B/1D) receptor agonist, which acts selectively on blood vessels of the brain. Short-term studies have demonstrated that almotriptan provides rapid, effective and reliable relief of migraine attacks, while offering excellent tolerability. PURPOSE: To assess the long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for every migraine attack over a 1-year period. METHODS: A total of 762 patients treated 13,751 attacks (1-97 per patient); 61.5% of attacks were treated with one 12.5-mg dose, while for 38.5% of attacks, patients took a second dose within 24 h. RESULTS: Three hundred and ninety-one patients (51.3%) experienced a total of 1,617 adverse events (AEs). The majority (88.6%) of AEs were of mild-to-moderate intensity, and only 28.8% of AEs were considered to be related to the study drug. Only 2 patients experienced serious AEs possibly related to almotriptan, syncope and chest pain; both recovered without any sequelae. Patients reported at least 1 AE in 11% of attacks treated. The incidence of AEs decreased during the study. Only 6 (0.8%) study withdrawals were due to AEs considered to be related to almotriptan. Tolerability was not compromised in patients taking 2 doses of almotriptan or in those using migraine prophylactics. Patient age or sex did not influence the incidence of AEs. There was no evidence of tachyphylaxis in those patients completing the study. Pain relief at 2 h after the initial dose was achieved in 84.2% of moderate/severe attacks. Patients were pain free at 2 h after dose in 58.2% of all attacks. Older patients (> 40 years) tended to respond better than younger ones (< 40 years). Efficacy was not modified by use of migraine prophylactics or hormonal contraceptives. Efficacy measurements were consistent on treating repeated moderate/severe migraine attacks. CONCLUSION: This large, open study indicates that the new, specific 5-HT(1B/1D) agonist almotriptan, at a dose of 12.5 mg, is a well tolerated and effective treatment for migraine pain when used over a period of up to 1 year.

Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study.

In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.

[Controlled study of iprazochrome effectiveness (Divascan) in prophylactic treatment of migraine]. / Kontrolowane badania skutecznosci iprazochromu (Divascan) w profilaktycznym leczeniu migreny.

The study was designed as double blind, placebo controlled. The patients were treated with 15 mg of iprazochrome daily in three equal doses for eight weeks, or--with equal amount of placebo tablets. The effectiveness was calculated with the use of Migraine Score (MS) by Couch et. al. 44 patients completed the study. In 21 the therapy was positive: 16 out of them were treated with iprazochrome, 5--with placebo. In 23 patients the treatment was negative: 19 out of them took placebo, 4--iprazochrome. Statistical analysis showed significant influence (chi 2 test: p < 0.001; Youle coeff. = 0.88). In iprazochrome group mean decrease of MS was significant after treatment (p < 0.01), but not significantly changed in the placebo group. According to our results iprazochrome was found effective in the prophylaxis of migraine.

[Sleep disorders--the problem with chrono-medicine]. / Zaburzenia snu--podstawowy problem chronomedycyny.

The aim of this paper is to present the clinical symptomatology and the methods of the therapy in the main sleep disorders: insomnia, narcolepsy and parasomnias.

[Drug rebound headaches]. / Polekowe bóle glowy "z odbicia".

The term "drug rebound headache" refers to headaches occurring every day in patients with migraine and tension headaches as a consequence of taking analgesics or ergotamine every day. Their cause is a vicious circle mechanism. This form of headache has been discovered in recent years and it is supposed that about 20% of patients with chronic headaches belong to that category. The only way to disrupt this vicious circle is immediate complete abandoning of these drugs. The abstinence period with associated troublesome symptoms lasts several to up to 20 days. Antidepressants are given for their alleviation. The author prescribes opipramol /Pramolan/ which is taken by increments from half tablet up to three in 6 days and the treatment is then continued for 4-6 weeks. From the 6th day on the patient should completely discontinue taking of analgesics. The material observed by the author comprises 47 patients /45 women/ aged 19-57 years, mean age 41 years, with these headaches continuing since 1-12 years /mean 3.0 years/. The above described method gave good results in 32 cases. In 10 cases complete withdrawal of analgesics was not possible by this method was abandoned accepting that their headaches were not due to drug abuse.

[Emergency treatment of migraine attacks with particular reference to agonists of 5-HT1B/1D receptor]. / Dorazne leczenie napadów migreny ze szczególnym uwzglednieniem agonistów receptora 5-HT1B/1D.

The author discusses the modern methods of emergency controlling of migraine attacks, especially the recently introduced drugs agonists of the 5-HT 1B/1D receptor /Sumatriptan, Zolmitriptan/ and prophylactic treatment. In light and moderately severe attacks analgesics are usually effective as well as non-steroid antiinflammatory drugs /paracetamol, acetylsalicylic acid, naproxen, diclofenac, ibuprofen, ketoprofen etc./ with or without addition of caffeine and codeine, and metoclopramide /for suppression of nausea and vomiting/ or Torecan. Ergotamine is still in use, although it can produce serious adverse effects. An essential advance in the treatment of more severe attacks was achieved with the introduction of Sumatriptan, a selective 5-HT1D receptor agonist in 1988. In pursuing this direction further indole derivatives /so called triptans/ were introduced. Zolmitriptan introduced in 1994 is an agonists of 5-HT 1B/1D receptor, is active both peripherally and centrally, is well absorbed from the digestive tract and has a good bioavailability index /40%/. In 2.5 mg doses it causes regression or marked alleviation of migraine attack within 2 hours in 70% of cases. Administration of a second dose after that time increases the percentage of successes. Adverse effects are usually mild, coronary complication have not yet been described. Prophylactic treatment is given to patients with attack frequency over 2 in a month. For that treatment usually dihydroergotamine, pisotifen, propranolol, metoprolol, flunarizin, valproic acid, iprasochrom and oxetoron are given.

[Selected problems for discussion of procedures in epilepsy]. / Wybrane dyskusyjne problemy postepowania w padaczce.

In neurological practice epilepsy treatment has a special place. Among the problems encountered by us in this connection every day the following are worth mentioning: Differential diagnosis of epileptic seizure against psychogenic fits and fainting. Management of the first seizure /treatment starting?/. How EEG tracings should be related to clinical status? Should imaging examination be suggested? Treatment programme /doses, mono- or polytherapy, new generation drugs/ Can anticonvulsants worsen epilepsy? Indications to surgical treatment. Whether and when anticonvulsants should be withdrawn in case of remission? Should treatment be given prophylactically after injury or stroke? How to deal with late onset epilepsy? What is the significance of concomitant diseases? The purpose of this lecture is to incite personal consideration of these matters and discussion on these problems in which it is difficult to take optimal decision.

[Insomnia and its treatment]. / Bezsennosc i jej leczenie.

Insomnia is a very frequent complaint /periodically or permanently it affects about 35% of the population/ and is a serious sociological problem. This term covers at least four types of sleep disorders: difficult falling asleep, frequent awakening, too early awakening and impairment of sleep quality--sleep quantitatively sufficient but failing to produce a feeling of rest. Insomnia may be sporadic, short-lasting and chronic. The last type requires particularly medical assistance since impairment of sleep quality can lead to drug dependence. In every case of insomnia it should be tried to explain its cause /neurosis, depression, somatic diseases with symptoms leading to sleep disturbances, toxic factors such as alcohol, drugs, inappropriate sleep hygiene etc./. In the treatment the basic role is played by removal of causes and better observation of sleep hygiene. Hypnotic drugs are indicated in sporadic and short-lasting insomnia, but in chronic insomnia they should be used cautiously and not continuously. Barbiturates have been abandoned recently and benzodiazepines have replaced them. They are, however, fraught with numerous faults. Cyclopyrolones /Zolpidem, Zopiklon/ are the new generation of hypnotic drugs in which the negative features of benzodiazepines have been partly excluded. Their half-life is short, they cause no rebound effect, adverse effects are better tolerated and are less frequent, drug dependence is not produced.

[Feverfew as a prophylactic treatment of migraine]. / Zastosowanie zlocienia maruny w profilaktycznym leczeniu migreny.

Feverfew has been used in traditional medicine in the treatment of migraine for a long time. In 1985 E.S. Johnson et al. and later J.J. Murphy et al., 1988 and B.K. Vogler et al., 1994 published positive results of prophylactic use of this herb in migraine. Since 1994 through 1996 we studied in our Centre of Migraine Therapy the efficacy of feverfew in migraine treatment. We had 24 patients (women 19-61 years old) in our group. The drug was administered once daily (5 ml of the sap) for 30-60 days. We observed significant reduction of Migraine Index in 8 patients, less significant in additional 5. Our results confirm that feverfew may be beneficial in migraine prophylaxis as an additive drug. Further controlled studies need to be done, especially to establish the optimal dose of the drug.

[Evaluation of efficacy and tolerance sumatriptan at a dose of 50 mg in treatment of migraine attack]. / Ocena skutecznosci i tolerancji sumatryptanu w dawce 50 mg w leczeniu napadu migreny.

Sumatriptan has been used successfully in the acute treatment of migraine since 1991. Most patients (70-80%) experience pain relief 2-4 hours after receiving 100 mg sumatriptan orally. During last few years efficacy of lower doses has been studied. Many authors proved that 50 mg of sumatriptan may be as effective as 100 mg. Our study confirmed that 50 mg oral dose of sumatriptan is sufficient in many patients. Headache relief was achieved in 58% of treated patients after single dose. The second dose of sumatriptan was effective in next 14% of patients. Totally headache relief after two doses of sumatriptan was achieved in 72% of patients. The sumatriptan 50 mg was well tolerated; only 10% of patients reported adverse events, which were minor and transient.

Preemptive oral treatment with sumatriptan during a cluster period.

This multinational, multicenter, randomized, double-blind, placebo-controlled study in 169 patients investigated the effect of a 7-day period of preemptive treatment with oral sumatriptan (100 mg tid) on the frequency and severity of cluster headache attacks occurring during an established cluster headache period. Safety and tolerability were also assessed. Cluster headache patients who were not taking prophylactic medication and had experienced seven or more attacks in the preceding observation week, treated a cluster headache attack at home with subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7-day period. Cluster headaches occurring during this period could be treated 5 minutes after onset with rescue medication (100% oxygen or simple analgesics). Diary cards were used to record details of the cluster headache pattern during the observation and study treatment weeks. Preemptive oral treatment with sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the number or severity of cluster headache attacks occurring during an established cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day period was not associated with an increased or altered adverse event profile from that previously reported.

[Ultrasound studies of blood flow velocity in main cranial arteries in idiopathic headaches]. / Badania ultrasonograficzne szybkosci przeplywu w duzych naczyniach mózgowych w samoistnych bólach glowy.

The published results of transcranial Doppler (TCD) studies of main cerebral arteries, performed in the patients with idiopathic headaches, especially with migraine, are controversial. Some authors could not find any changes, others observed increased blood flow. These results were, however, based on single examination, and the comparison on mean velocities calculated for the whole groups. In the present study the authors decided to perform a series of TCD studies in each patient and to analyse the individual cases. It was found that blood flow velocity in the main cerebral arteries in chronic tension-type headache (8 cases) and cluster headache (7 cases) showed normal values, established for 35 healthy subjects. In migraine without aura (20 cases) and with aura (11 cases) a considerable increase (above 30%) in cerebral blood flow was found in some studies. In around 50% of the cases increased blood flow in anterior and middle cerebral arteries was found unilaterally. The authors believe that the above findings might be specific for migraine and reflect transient vasoconstriction of the vessels that, on the other head, may be the premonitory laboratory sign of the attack.

[Current views on pathophysiology of migraine. Part IV: autonomic disturbances. Central neural hypothesis. Conclusions]. / Wspólczesne poglady na patogeneze migreny. Czesc IV: Zaburzenia autonomiczne. Hipotezy osrodkowe. Podsumowanie.

The last part of the article concerns the role of the disturbances of autonomic system and central neural hypothesis of migraine pathogenesis. The author presents the results of studies on pupillometry and autonomic heart regulation, that seem to indicate hypofunction of the autonomic system in migraine. The views on "neurogenic inflammation", as the basic pathologic phenomenon in migraine attack are also discussed, as well as the hypothesis of cortical spreading depression. In the conclusions the author find that neither theory can convincingly explain the pathogenesis of migraine. The updated studies seem to indicate both vascular, autonomic and central neural factors in, possibly multifactorial, pathogenesis of migraine.

[Current views on pathophysiology of migraine: Part I. Genetics of migraine. Genesis of the vascular theory]. / Wspólczesne poglady na patogeneze migreny Czesc I: Wprowadzenie. Genetyka migreny. Rozwój teorii naczyniowej.

The studies on the pathogenesis of migraine have developed into a vast scientific movement in last years. The author discusses throughly the results of these studies. In the first part of the paper the genesis and development of the vascular theory of migraine pathogenesis is presented.

[Sodium valproate versus propranolol in the prophylactic treatment of migraine]. / Porównanie dzialania soli sodowej kwasu walproinowego i propranololu w leczeniu profilaktycznym migreny. Doniesienie wstepne.

In the recent years sodium valproate (SV) has been proposed as a prophylactic drug in migraine. Several reports documented a positive effect of SV in migrainous patients. The authors present the results of the open study in 35 women with migraine without aura treated with the daily dose of 1000-1500 mg of SV, during 10 weeks. The results were compared with the effect of propranolol administered to the same patients, in daily dose of 120-160 mg during 10 weeks. The effects were similar: in both methods more than 50% reduction of frequency and severity of attacks was obtained. The side effects were generally mild; in no case the treatment was stopped. The authors conclude that in the future SV might be administered in migraine prophylaxis as the first choice drug.

[Automatic regulation of sinus rhythm in patients with migraine]. / Automatyczna regulacja rytmu zatokowego serca u chorych z migrena.

The clinical symptoms of migraine point to autonomic disturbances, especially to disrupted regulation of the circulatory system and autonomic balance. Searching for more accurate autonomic system studies we turned to the spectral analysis of cardiac rhythm changes, that allows to estimate the autonomic balance in sinus node. 44 patients with migraine were studied and the results were compared with those obtained in 74 healthy subjects. The reduced influence of both sympathetic and parasympathetic part of autonomic system on the sinus rhythm in migraine patients was found. The autonomic balance is shifted to the parasympathetic innervation side in patients with migraine.

[The comparison of sodium valproate and ergotamine titrate plus caffeine in the abortive treatment of migraine attacks]. / Porównanie dzialania soli sodowej kwasu walproinowego i winianu ergotaminy z kofeina w doraznym leczeniu napadów migreny. Doniesienie wstepne.

The contemporary measures against migraine attacks are not fully satisfying, thus the migraine episode is still a challenge in treatment. In 1993 Hering and Steiner proposed valproic acid for the interruption of migraine attacks. The authors present the results of their own study comparing the effects of sodium valproate (SV) and ergotamine plus caffeine (Coffecorn) in this respect. 82 attacks in 20 patients were treated altogether. The effectiveness of SV was statistically not different from that of ergotamine--the drug recognized formerly as the first choice one in the abortion of migraine attacks.

[Current views on pathophysiology of migraine. Part II: Further development and current status of the vascular theory. Migraine and allergy]. / Wspólczesne poglady na patogeneze migreny. Czesc II: Dalszy rozwój i stan obecny teorii naczyniowej. Migrena i alergia.

In this part further arguments advocating the vascular theory are discussed, among others: the influence of drugs (ergotamine, sumatriptan), so called "migrainous stroke", and the results of the last neuroimaging studies on the migraine. The authors state in summary that vascular disturbances do take place in migraine attack, but they should be regarded in connection with biochemical and central neuronal disorders. In the end the authors discusse the current views on the impact of allergy in the pathophysiology of migraine.