Reduction In Frequency Of Attacks Research Articles

Robust randomised control trials needed for drug treatments for trigeminal neuralgia

Searches for appropriate studies were made using the following: Cochrane Neuromuscular Disease Group Register, Medline, Embase and LILACS (Latin American and Caribbean Literature on the Health Sciences) together the Chinese Biomedical Retrieval System, the database of the Chinese Cochrane Centre, conference paper databases and checked bibliographies. 10 Chinese journals were searched by hand. Randomised controlled trials (RCT) or quasi-randomised controlled trials were included. Two authors decided which trials fitted the inclusion criteria and graded methodological quality independently. Nine trials of different non-antiepileptic drugs involving 223 participants were included. Each trial investigated one non-antiepileptic drug. Two trials tested baclofen. In one, more people achieved 50% reduction from baseline than with placebo [relative risk (RR), 15.00; 95% confidence interval (CI), 0.97-231.84; P 0.05]. In the other, slightly more participants who took baclofen showed a 75% reduction in attacks on the tenth day compared with carbamazepine (RR, 2.38; 95% CI, 0.83-6.85; P 0.11). One trial showed no significant difference in reduction in average daily frequency of attacks with Baclofen compared with Racemic Baclofen. Tizanidine was investigated in two trials. In one, the proportion of people with a reduction in the mean number of paroxysms per day increased with tizanidine compared with placebo (RR, 8.00; 95% CI, 1.21-52.69; P 0.03). In the other, one of five participants improved their visual analogue scale score with tizanidine and four of six did so having taken carbamazepine (RR, 0.30; 95% CI, 0.05-1.89; P 0.20). One study showed that the improvement in mean values of pain scores with tocainide was similar to that of carbamazepine. In a further trial, more participants improved during the pimozide than the carbamazepine period (RR, 1.78; 95% CI, 1.39-2.28). In another, a 0.5% instillation of proparacaine hydrochloride into the eyes did not produce significantly different results from placebo (RR, 1.06; 95% CI, 0.37-2.99; P 0.92). Finally, there was moderate or marked improvement in a study in seven of nine participants who took clomipramine and three of nine who took amitriptyline during a 12-week treatment (RR, 2.33; 95% CI, 0.87-6.27). Trials of non-antiepileptic drugs for treating trigeminal neuralgia have all been limited by poor methodological quality or poor reporting. There is insufficient evidence from randomised clinical trials to show significant benefit from non-antiepileptic drugs for trigeminal neuralgia.

A Randomized Double‐Blind Placebo‐Controlled Trial of Thioctic Acid in Migraine Prophylaxis

Impaired mitochondrial phosphorylation potential may play a role in migraine pathogenesis. Metabolic enhancers, such as riboflavin or coenzyme Q, are effective in migraine prophylaxis and quasi-devoid of adverse effects. Thioctic acid (-lipoic acid) is another substance known to enhance energy metabolism in mitochondria and to be beneficial in diabetic neuropathy. After an open pilot study suggesting its therapeutic antimigraine potentials, we embarked therefore in a randomized controlled trial of thioctic acid (Thioctacid) in migraine prophylaxis steered by the Belgian Headache Society. Five Belgian centers recruited 54 migraineurs (43 migraine without aura, 11 with aura; mean age 38 +/- 8 years; 7 males). After a 1-month single-blinded run-in period, 44 patients received either placebo (n = 18) or thioctic acid 600 mg p.o./day (n = 26) for 3 months. Statistical analysis was carried out on an intention-to-treat basis. Monthly attack frequency tended to be reduced between run-in and the 3rd month of treatment in the thioctic acid group compared to placebo (P= .06). The proportion of 50% responders was not significantly different between thioctic acid (30.8%) and placebo (27.8%). Within-group analyses showed a significant reduction of attack frequency (P= .005), headache days (P= .009), and headache severity (P= .03) in patients treated with thioctic acid for 3 months, while these outcome measures remained unchanged in the placebo group. No adverse effects were reported. For logistical reasons this trial was interrupted before the planned 80 patients were enrolled. Albeit underpowered, this study tends to indicate that thioctic acid may be beneficial in migraine prophylaxis. Before any firm conclusion can be drawn, however, a large multicenter trial is necessary.

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A

Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX-A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non-responders to BTX-A treatment were compared prospectively ( n = 27) and retrospectively ( n = 36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0 ± 1.7 before BTX-A to 0.8 ± 0.3 after BTX-A (down 95.3 ± 1.0%) in 39 responders, and remained unchanged (11.3 ± 1.9 vs. 11.7 ± 1.8) in 24 non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non-responders. However, the two groups offered different accounts of their pain. Among non-responders, 92% described a buildup of pressure inside their head ( exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces ( imploding headache), and 13% attested to an eye-popping pain ( ocular headache). The finding that exploding headache was impervious to extracranial BTX-A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX-A treatment suggests that these types of migraine pain involve extracranial innervation as well.

Migraine - a suitable case for treatment?

Migraine - a suitable case for treatment?

The Preventive Treatment of Migraine

Migraine is a common, chronic, and disabling disorder. The treatment of migraine includes a combination of nonpharmacologic and pharmacologic techniques. Pharmacologic approaches are subdivided in preventive therapies and acute care. In this review article, we review the current approaches to the preventive treatment of migraine. Preventive treatment should be initiated in those with frequent or disabling headaches. The goals include (1) reducing attack frequency, intensity, and duration; (2) minimizing headache-related disability; (3) improving health-related quality of life; (4) avoiding headache escalation and medication misuse. In this article, we also discuss the principles of migraine prevention, as well as drugs available for this goal. We divide preventive medications on those of common use, nutraceutical compounds, and medications less frequently used. We close by briefly discussing some in-development potential preventive drugs. Preventive therapies are well suitable for migraineurs with attack-related disability despite appropriate acute care.

Phosphodiesterase Inhibitors in Raynaud's Phenomenon

To evaluate the efficacy of the phosphodiesterase type 5 (PDE5) inhibitors in the treatment of Raynaud's phenomenon. Searches of MEDLINE (1966-March 2006) and Web of Science (1980-March 2006) were conducted; search terms were sildenafil, tadalafil, vardenafil, phosphodiesterase, and Raynaud. Studies and case reports published in English were retrieved. Additional references were identified in bibliographic reviews. Several small studies and a number of case reports have described the use of PDE5 inhibitors in patients with either primary or secondary Raynaud's phenomenon. The data from the best designed study show a reduced attack frequency and duration, reduced Raynaud Condition Score, and increased capillary blood flow in patients with secondary Raynaud's phenomenon. Available evidence suggests that sildenafil may be associated with improved microcirculation, symptomatic relief, and ulcer healing in patients with secondary Raynaud's phenomenon. Limited information suggests similar effects with tadalafil and vardenafil. Improved blood flow and clinical improvements have also been observed in some patients with primary Raynaud's phenomenon treated with PDE5 inhibitors; however, studies have yielded conflicting results.

Long-term experience with interferon beta-1b (Betaferon®) in multiple sclerosis

The interferon beta-1b (IFNbeta-1b, Betaferon/Betaseron) molecule was cloned some 20 years ago. In a pilot dose-finding trial involving 30 multiple sclerosis (MS) patients, the 10 MS patients receiving 250 microg (8 MIU) IFNbeta-1b every other day at 6 months showed a reduced attack frequency relative to 6 patients receiving placebo. Based on these extremely preliminary results a Phase III placebo-controlled trial was undertaken. Treatment with IFNbeta-1b was shown to reduce attack frequency and severity and to markedly reduce magnetic resonance imaging-(MRI) measured activity and disease burden. IFNbeta-1b therapy was subsequently shown to reduce MRI activity within 2 weeks of starting treatment. The benefits of treatment with IFNbeta-1b observed in the original pivotal study are maintained in the longer term, with consistent treatment effects seen after 5 years. IFNbeta-1b has subsequently been shown to reduce accumulation of disability in MS patients with early active secondary progressive disease, to increase cerebral metabolism, and to improve cognitive performance.IFNbeta-1b therapy is generally well tolerated. Classical systemic side effects related to all beta interferons can effectively be managed by dose escalation, and the use of an autoinjector minimises injection site reactions. About one-third of MS patients receiving IFNbeta-1b develop anti-interferon antibodies, typically within the first year of therapy. These antibodies have variable titres that fall with time and ultimately disappear in most patients. The clinical consequences of the presence of antibodies are presently unclear and inconsistent-some patients without antibodies respond poorly to treatment, whereas others with high-titre antibodies respond well to treatment. It is possible that immune complexes formed when anti-interferon antibodies encounter IFNbeta may enhance some of the immunomodulatory actions of the drug by improving CD8 cell-mediated suppressor function. Until the clinical relevance of antibodies is better understood, treatment decisions should be based on clinical grounds only.

Non pharmaceutical treatments for migraine

The target of non-drug treatment of migraine is to reduce attack frequency and intensity. To reach this goal, the general relationship between the patient and the physician, i.e. the drug consumer and prescriber, has to be changed fundamentally. To understand migraine attacks the patient must learn to distinguish between the cause of migraine, a special readiness of the brain to react, and the triggers of a headache attack. Today, we have access to effective methods that prevent inherited migraine from coming to an effect, or to effectively arrest an attack if it has nevertheless broken out. There are three available strategies: prevention by avoiding trigger factors, prevention via reduction of attack readiness and treatment of the acute effects of the migraine attack.

Potassium Channel Blockers Inhibit the Triggers of Attacks in the Calcium Channel Mouse Mutanttottering

Humans with the disorder episodic ataxia type 2 (EA2) and the tottering mouse mutant exhibit episodic attacks induced by emotional and chemical stress. Both the human and mouse disorders result from mutations in CACNA1A, the gene encoding the alpha(1)2.1 subunit of Ca(v)2.1 voltage-gated calcium channels. These mutations predict reduced calcium currents, particularly in cerebellar Purkinje cells, where these channels are most abundant. 4-Aminopyridine (4-AP), a nonselective blocker of K(v) voltage-gated potassium channels, alleviates attacks of ataxia in EA2 patients. To test the specificity of the effect for K(v) channels, aminopyridine analogs were assessed for their ability to ameliorate attacks of dyskinesia in tottering mice. 4-AP and 3,4-diaminopyridine (3,4-DiAP), which have relatively high affinities for K(v) channels, reduced the frequency of restraint- and caffeine-induced attacks. Furthermore, microinjection of 3,4-DiAP into the cerebellum completely blocked attacks in tottering mice. Other aminopyridine analogs reduced attack frequency but, consistent with their lower affinities for K(v) channels, required comparatively higher doses. These results suggest that aminopyridines block tottering mouse attacks via cerebellar K(v) channels. That both stress- and caffeine-induced attacks were blocked by aminopyridines suggests that these triggers act via similar mechanisms. Although 4-AP and 3,4-DiAP were effective in preventing attacks in tottering mice, these compounds did not affect the severity of "breakthrough" attacks that occurred in the presence of a drug. These results suggest that the aminopyridines increase the threshold for attack initiation without mitigating the character of the attack, indicating that attack initiation is mediated by mechanisms that are independent of the neurological phenotype.

Petasites hybridus root (butterbur) is an effective preventive treatment for migraine

To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine. This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period. Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping. Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.

Efficacy of flunarizine in the prophylaxis of cyclical vomiting syndrome and abdominal migraine

Cyclical vomiting syndrome (CVS), and abdominal migraine (AM) are relatively unusual periodic syndromes, generally believed to be migraine equivalents, and are characterized by recurrent and severe paroxysmal episodes of vomiting and/or abdominal pain lasting hours to days, separated by weeks to months of no symptoms. Flunarizine is a calcium channel-blocking agent that has been used successfully as a prophylactic agent in the prevention of both childhood and adult-onset migraine syndromes. The purpose of this study was to evaluate the efficacy of flunarizine as a prophylactic/preventive agent in the treatment of CVS and AM. Eight children with CVS and 10 children with AM were included in the study. The mean dose of flunarizine was 5 mg/day in children with CVS, and 7.5 mg/day in children with AM. Follow-up ranged from 6 to 24 months (mean 13 months). There was a 57% reduction in frequency and 44% reduction in duration of attacks of CVS, and a 61% reduction in frequency and 51% reduction in duration of attacks of AM. Sixty-four percent of patients with CVS and AM had history of episodic recurrent headaches with 60% reduction in frequency of attacks on treatment. Flunarizine showed to be equally efficacious than previously tried therapies in the prophylaxis of a small cohort of patients with CVS and AM.

The medical management of migraine.

Migraine is a common, chronic neurologic disorder that affects 11% of the adult population in Western countries. In this article, we review the current approaches to the pharmacologic treatment of migraine. Once migraine is diagnosed, and illness severity has been assessed, clinicians and patients should work together to develop a treatment plan based on the patient needs and preferences. The goals of the treatment plan usually include reducing attack frequency, intensity, and duration; minimizing headache-related disability; improving health-related quality of life; and avoiding headache escalation and medication misuse. Medical treatments for migraine can be divided into preventive drugs, which are taken on a daily basis regardless of whether headache is present, and acute drugs taken to treat individual attacks as they arise. Acute treatments are further divided into nonspecific and migraine-specific treatments. The US Headache Consortium Guidelines recommend stratified care based on the level of disability to help physicians individualize treatment. Simple analgesics are appropriate as first-line acute treatments for less disabled patients; if simple analgesics are unsuccessful, treatment is escalated. For those with high disability levels, migraine-specific acute therapies, such as the triptans, are recommended as the initial treatment, with preventive drugs in selected patients. A variety of behavioral interventions are helpful. The clinicians have in their armamentariums an ever-expanding variety of medications. With experience, clinicians can match individual patient needs with the specific characteristics of a drug to optimize therapeutic benefit.

The PROMISE Study: PROphylaxis of MIgraine with SEglor?? (Dihydroergotamine Mesilate) in French Primary Care

Seglor capsules, a unique modified-release formulation of dihydroergotamine mesilate, have long been in clinical use in France for migraine prophylaxis. The aim of the PROMISE (PROphylaxis of MIgraine with SEglor) study was to establish the efficacy and tolerability of Seglor in the prevention of migraine in a general practice setting. The PROMISE study was a double blind, placebo-controlled, parallel-group study carried out in primary care practice. It included 363 migraine patients treated with Seglor or placebo for 5 months after a 1-month placebo run-in phase. Migraine attack frequency (primary efficacy criterion) decreased markedly in the two treatment groups so that the difference in favour of Seglor did not reach statistical significance. However, most secondary outcome measures (duration of single attack, total duration of attacks over 1 month, consumption of mild opiate analgesics, subjective improvement) improved to a significantly greater degree in patients receiving Seglor than in those receiving placebo. In the 84.5% of patients who had impaired quality of life at entry, the percentage of reduction in attack frequency and most other efficacy measures showed significant improvement with Seglor. The safety profile for Seglor was comparable to that of placebo. These results support the effectiveness of Seglor in patients with migraine-related quality-of-life impairment. The findings of the PROMISE study also suggest that patients' quality of life should be assessed systematically before initiating a preventive treatment for migraine.

Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis.

Multiple sclerosis can be associated with trigeminal neuralgia which is often difficult to treat in this specific condition. We performed an open prospective trial on the efficacy and safety of the prostaglandin-E1-analogue misoprostol (600 microg per day) in the reduction of attack frequency and pain intensity in patients with refractory trigeminal neuralgia associated with multiple sclerosis. Eighteen patients completed the study period and 14 of them showed a reduction of more than 50 % in attack frequency and intensity beginning five days after treatment onset. There were only mild and transient drug related side effects in three patients. One patient stopped taking misoprostol after the study period because of severe menorrhagia. Our results suggest that misoprostol is effective and safe in the treatment of this specific type of refractory trigeminal neuralgia.

Migraine: preventive treatment.

Migraine is a common episodic headache disorder. A comprehensive headache treatment plan includes acute attack treatment to relieve pain and impairment and long-term preventive therapy to reduce attack frequency, severity, and duration. Circumstances that might warrant preventive treatment include: (i) migraine that significantly interferes with the patient's daily routine despite acute treatment; (ii) failure, contraindication to, or troublesome side-effects from acute medications; (iii) overuse of acute medications; (iv) special circumstances, such as hemiplegic migraine; (v) very frequent headaches (more than two a week); or (vi) patient preference. Start the drug at a low dose. Give each treatment an adequate trial. Avoid interfering, overused, and contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing potential is aware of any potential risks. Involve patients in their care to maximize compliance. Consider co-morbidity. Choose a drug based on its proven efficacy, the patient's preferences and headache profile, the drug's side-effects, and the presence or absence of coexisting or co-morbid disease. Drugs that have documented high efficacy and mild to moderate adverse events (AEs) include beta-blockers, amitriptyline, and divalproex. Drugs that have lower documented efficacy and mild to moderate AEs include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate, riboflavin, and non-steroidal anti-inflammatory drugs.

Multiple sclerosis.

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system (CNS). Diagnosis rests upon identifying typical clinical symptoms and interpreting supportive laboratory and radiological investigations. The etiology is unknown; however, strong evidence suggests that MS is an autoimmune disease directed against CNS myelin or oligodendrocytes. Genetic factors are important in the development of MS. Contributing environmental determinants (possibly including infectious agents) appear important but remain unidentified. Both cell-mediated and humorally mediated immune mechanisms contribute to pathological injury. Axonal damage occurs in addition to demyelination and may be the cause of later permanent disability. Distinct pathological subtypes may differentiate among patients with MS. Treatment is directed at acute attacks (with corticosteroids) and reduction of attack frequency (primarily with type-1 beta interferons and glatiramer acetate). Research into the causes and treatments of MS has expanded our knowledge of this disease and promises improved care for MS patients in the future.

A comparative study of magnesium, flunarizine and amitriptyline in the prophylaxis of migraine

Circumstantial evidence points to the possible role of magnesium (Mg+2) deficiency in the pathogenesis of migraine and has raised questions about the clinical utility of magnesium as a therapeutic regimen in migraine. This was a prospective, randomized, double-blind, placebo-controlled trial comparing the efficacy and tolerability of 1830 mg magnesium citrate (23 patients), 10 mg flunarizine (22 patients) and 10 amitriptyline (20 patients) in the prophylaxis of migraine diagnosed according to the criteria of the International Headache Society. Patients were evaluated for attack frequency, severity and drug side effects monthly for 3 months. Magnesium, flunarizine and amitriptyline were all superior to placebo (p<0.001) in reducint both attack frequency and severity after the first month. There was no significant difference between the 3 active drugs in reduction of attack frequency and severity. No serious side effects were observed and the frequencies of side effects were not significantly different in all treatment groups. Our results show that oral magnesium is an effective and well tolerated drug in the prophylaxis of migraine and compares well to established drugs like flunarizine and amitriptyline both in effectiveness and occurence of side effects. Magnesium may be an alternative drug in migraine prophylaxis, but more and larger comparative trials are needed to confirm these results.

Verapamil reduced attack frequency and the use of abortive agents in episodic cluster headache

(2000) Neurology 54, 1382. Leone M, D'Amico D, Frediani F . , et al . . Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo ....

Verapamil reduced attack frequency and the use of abortive agents in episodic cluster headache

Verapamil reduced attack frequency and the use of abortive agents in episodic cluster headache

Effective prophylactic therapy for cyclic vomiting syndrome in children using amitriptyline or cyproheptadine.

To evaluate our experience using the antimigraine prophylactic drugs, amitriptyline and cyproheptadine, for the prophylactic management of cyclic vomiting syndrome (CVS) in children. Twenty-seven patients (16 males) ranging in age from 2 to 16 years at diagnosis, fulfilling the diagnostic criteria for CVS and treated prophylactically with either amitriptyline (22) or/and cyproheptadine (6) were identified through retrospective chart review. Individual patient data were corroborated by the attending physician and/or interviews with patients and families. Minimum follow-up time before entry into the study group was 5 months. Patients were stratified according to three treatment outcomes: 1) complete response-no attacks, 2) partial response-50% or greater reduction in frequency of attacks, and 3) no response-less than 50% decrease in frequency of attacks. Of the 22 patients treated with amitriptyline, 16 (73%) had a complete response while 4 (18%) had a partial response. Of the 6 patients treated with cyproheptadine, 4 (66%) had a complete response and 1 (17%) had a partial response. Thus, 91% of the amitriptyline group and 83% of the cyproheptadine group had at least a partial response to therapy. No patients experienced significant side effects to either medication. The antimigraine prophylactic drugs, amitriptyline and cyproheptadine, represent effective prophylactic agents for the management of CVS in the vast majority of patients fulfilling the diagnostic criteria for this syndrome.