Analysis of Safety and Tolerability Data Obtained from Over 1,500 Patients Receiving Topiramate for Migraine Prevention in Controlled Trials

Objective.  Topiramate is an effective and generally well-tolerated migraine preventive therapy, as shown in three large, randomized, double-blind, placebo-controlled registration trials. Based upon efficacy/tolerability, topiramate 100 mg/day (50 mg BID) is the recommended target dose for most patients with migraine. To further assess the safety and tolerability of topiramate for migraine prevention, we analyzed safety data from 1,580 patients who participated in the three pivotal registration trials or an earlier pilot, randomized, double-blind, placebo-controlled trial. Methods.  The safety population consisted of all patients who took ≥1 dose of study medication during the double-blind …

Rizatriptan in the treatment of migraine.

Migraine is a common, disabling disorder associated with considerable personal and societal burden. Current guidelines recommend triptans for the acute treatment of migraine unlikely to respond to less effective therapies. Rizatriptan is a second-generation triptan available in tablet or orally disintegrating tablet (wafer) formulations that offers several advantages over other members of its class. Rizatriptan is rapidly absorbed from the gastrointestinal tract and achieves maximum plasma concentrations more quickly than other triptans, providing rapid pain relief. Clinical trials have shown that rizatriptan is at least as effective or superior to other oral migraine-specific agents in the…

Validity and reliability of the Migraine-Treatment Optimization Questionnaire.

Our aim was to establish the validity and reliability of a patient-rated Migraine Treatment Optimization Questionnaire (M-TOQ in primary care. Patients who met International Classification of Headache Disorders, 2nd edn criteria for migraine completed a 19-item questionnaire containing candidate items for the M-TOQ and three questionnaires designed to test convergent/construct validity [Migraine Disability Assessment Scale (MIDAS), Headache Impact Test (HIT)-6 and Migraine-Specific Quality of Life Scale (MSSQoL)]. A 15-item (M-TOQ15) and a five-item (M-TOQ-5) questionnaire were derived. Two hundred and fifty-three adult patients were recruited. Five treatment optimization domains were iden…

Stimulation of the sphenopalatine ganglion in intractable cluster headache: expert consensus on patient selection and standards of care.

Context and overview Chronic cluster headache (CCH) is a debilitating headache disorder with a significant impairment of the patients' lives. Within the past decade, various invasive neuromodulatory approaches have been proposed for the treatment of CCH refractory to standard preventive drug, but only very few randomized controlled studies exist in the field of neuromodulation for the treatment of drug-refractory headaches. Based on the prominent role of the cranial parasympathetic system in acute cluster headache attacks, high-frequency sphenopalatine ganglion (SPG) stimulation has been shown to abort ongoing attacks in some patients in a first small study. As preventive effects of SPG-sti…

Pathway CH-1 Study: Sphenopalatine Ganglion (SPG) Stimulation for Acute Treatment of Chronic Cluster Headache (CCH) - Initial Experience (S36.002)

Objective: We aimed to investigate the safety and efficacy of SPG stimulation for the acute treatment of CCH. Background The pain and autonomic symptoms of cluster headache result from activation of the trigeminal parasympathetic reflex, mediated through the SPG. Design/Methods: A multi-center, dose range finding, multiple headache attack (HA), acute treatment study with random insertion of placebo has been initiated. All subjects meet the ICHD-II criteria for CCH with a minimum of 4 HAs/week. Subjects are implanted with a miniaturized neurostimulator which, along with a controller, provides SPG stimulation. Prior to the randomized period, stimulation parameters are adjusted in a titration …

Diagnosis of Tinnitus: Neurological Examination

1. There is an urgent need for a set of assessment methods to be agreed upon and utilized by the international tinnitus research community. 2. Neurological examination of tinnitus patients is essential to achieve a good diagnostic approach to the different forms of objective and subjective tinnitus. 3. This chapter summarizes the neurological examination in tinnitus, including the protocol used in the authors’ tinnitus clinic, which is based on the consensus of the Tinnitus Research Initiative (TRI).

Cost-efficacy of oral triptans in the treatment of acute migraine

SummaryThe objective of this study was to compare the efficiency of oral triptans currently used in the treatment of acute migraine in Spain. Using a decision analytic model, a cost-efficacy analysis was performed from the payer's perspective. Efficacy was assessed in terms of sustained pain-free patients, with data extracted from a recent meta-analysis of clinical trials. Chest-related and central nervous system-related adverse events were also considered. For the economic analysis, the cost of drug treatment and the management of adverse events were determined.A group of three triptans (naratriptan 2.5 mg, sumatriptan 50 mg and almotriptan 12.5 mg) was found to dominate all other triptans…

Causes of Tinnitus: Cerebrovascular Diseases

1. Tinnitus can be divided into two broad groups: objective and subjective tinnitus. 2. Several layers of complexity are involved in the pathophysiology and the cause of tinnitus, and it is rarely known what causes an individual’s tinnitus. 3. Disorders that affect the brain are often accompanied by tinnitus. 4. Cerebrovascular diseases can be the cause of both objective and subjective tinnitus. 5. This chapter discusses cerebrovascular diseases as a cause of tinnitus and how it is produced.

Tinnitus Treatment: Botulinum Toxin

1. Somatosensory tinnitus (objective or subjective) is tinnitus that can be modulated by stimulation of the somatosensory system. 2. Abnormal interactions between the auditory and the somatosensory nervous system that may occur at several levels of the central nervous system cause somatosensory tinnitus. 3. This chapter discusses how administration of a ­botulinum toxin can alleviate tinnitus and the mechanism of its action, and how that relates to its effects on chronic pain. 4. A proven benefit of botulinum toxin in patients with objective tinnitus is also discussed.

Botulinum toxin for the treatment of somatic tinnitus

Subjective tinnitus is an auditory sensation experienced in the absence of external or internal acoustic stimuli. It causes significant morbidity and can progress to a chronic debilitating condition. Somatic tinnitus is tinnitus that can be modulated by stimulation of the somatic sensory system. It occurs because of interactions between the auditory and the somatosensory system that may occur at several levels of the central nervous system. In the present chapter, we discuss how botulinum toxin can improve tinnitus and discuss the mechanism of its action, and how it relates to its effects on chronic pain.

Clinical Description of a Different Form of Tinnitus: Intermittent Tinnitus

1. Intermittent (paroxysmal) tinnitus is a form of non-pulsatile tinnitus. 2. An intermittent nature can be the only sign that intermittent tinnitus is different from other forms of tinnitus. 3. Intermittent tinnitus may be accompanied by irregular symptoms of other neurotologic disorders. 4. Both objective and subjective tinnitus may be intermittent. 5. A wide range of pathologies may cause intermittent tinnitus, but the cause of most forms is unknown.

Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy

In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was as…

Headache attributed to head or neck trauma

Publisher Summary This chapter presents an overview of all types of posttraumatic headache (PTH): acute PTH, chronic PTH, and headache after a whiplash injury, taking account of the definition and latest criteria of International Headache Classification II (ICHD-II). Headache is a symptom that may occur after injury to the head, neck, or brain. PTH is a cardinal symptom of the “postconcussion syndrome” and may be accompanied by somatic, psychological, or cognitive disturbances. PTH is always a new-onset headache resulting from brain, head, and sometimes neck injury, and can simulate the clinical characteristics of several primary headaches. Severe, moderate, and mild head injuries can cause…

Efficacy of Therapeutic Intervention in Headache Units in Patients With Frequent Headaches: The EFUNCE Study

Data confirming that therapeutic intervention in headache units is superior to care received by patients in other levels of the health system are scant. This is a pilot study that includes patients seen in 4 headache units for at least 1 year, who had a headache frequency of more than 15 days per month. The results of the first 30 patients showed a significant improvement in different headache parameters and a high degree of satisfaction with the treatment received.

The impact of a worksite migraine intervention program on work productivity, productivity costs, and non-workplace impairment among Spanish postal service employees from an employer perspective.

Migraine is associated with a significant productivity loss to employers, who may benefit from making a migraine intervention available to their employees.To evaluate changes in migraine-related productivity and non-workplace impairment associated with a migraine intervention program from the employer perspective.This was a pre-test post-test study of Spanish Postal Service employees with migraine. The intervention consisted of counseling from occupational health physicians and rizatriptan 10 mg for symptomatic treatment of two subsequent migraine headaches. Physicians also prescribed additional medications for migraine prophylaxis, treatment of tension headaches, and rescue medications. Mi…

Clinical Benefits of Early Triptan Therapy for Migraine

The introduction of the triptans brought advances in achieving complete and sustained pain resolution in migraine patients, compared with non-migraine-specific treatments. However, sustained pain-free rates for triptans recorded in many clinical trials are still relatively low. This may be due to study participants being treated late into the attack, when pain is already moderate or severe. Studies with almotriptan have shown that efficacy is enhanced when treatment is given early in a migraine attack while pain is still mild, compared with later administration when pain intensity is greater. Developments in our understanding of migraine pathophysiology provide a rationale for this phenome…

Stratified Care vs Step Care Strategies for Migraine

ContextVarious guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated.ObjectiveTo compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine.Design and SettingRandomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical cen…

Tinnitus with Headaches

1. Patients with tinnitus frequently have headaches, but the relation between these two disorders is not always casual. 2. Headaches and tinnitus could be symptoms of the same disease. 3. Idiopathic intracranial hypertension is a syndrome in which headaches and tinnitus often occur together. 4. Headaches and tinnitus often occur together with other focal symptoms in symptomatic intracranial hypertension. 5. Intracranial vascular abnormalities such as arteriovenous malformations (AVMs) can occur together with any kind of headache with paroxysmal tinnitus. 6. Tinnitus may be one of the signs of a basilar migraine. 7. Headaches are a very frequent symptom after head trauma, and tinnitus is als…

Preference for Rizatriptan 10-mg Wafer vs. Eletriptan 40-mg Tablet for Acute Treatment of Migraine

Preference is a composite, patient-oriented endpoint incorporating efficacy, tolerability, formulation, and convenience of medications. The objective of this study was to compare patient preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine. In this multicentre, open-label, two-period, crossover study, out-patients were randomly assigned to treat the first of two moderate to severe migraines with rizatriptan or eletriptan and the second with the alternate therapy. Patients completed diary assessments at baseline and up to 24 h after taking study medication. At the last visit, patients completed a psychometrically validated preference questionnai…

Treatment Strategies for Migraine Headache

The Effect of Migraine Prophylaxis on Migraine-Related Resource Use and Productivity

In the US, it is estimated that up to 10% of men and 25% of women, particularly those aged 25-55 years, experience debilitating migraines, such that the condition presents an enormous economic burden for patients, health systems, employers and society. Migraine headache is a particularly prevalent condition associated with major reductions in patients' quality of life. From a payer perspective, the implementation of relevant programmes of migraine prophylaxis is highly desirable. Consistent evidence exists, from several randomized, controlled studies, of the efficacy of amitriptyline, divalproex sodium, propranolol, timolol and topiramate in migraine prophylaxis. Considering resource utiliz…

Antiepileptic Drugs for the Treatment of Chronic and Episodic Cluster Headache: A Review.

Cluster headache needs to be rapidly diagnosed and effectively managed, as the individual headache attacks that are characteristic of this disorder are excruciatingly painful and debilitating. Preventive therapies are necessary to reduce the frequency of attacks during the cluster period. However, preventive therapy for this disorder is limited by a lack of controlled evidence of efficacy and the potential for systemic toxicity. Recent progress has been made in understanding both the pathophysiological mechanisms underlying cluster headache and the mechanisms of action of the antiepileptic drug class for the treatment of primary headache syndromes. Newly available preliminary clinical trial…

Topiramate in migraine prophylaxis

Many of the drugs available for the prophylaxis of migraine never underwent rigorous placebo-controlled trials, and the effective drugs have side effects that are problematic in daily practice. Three double-blind studies involving more than 1500 patients (the largest clinical development program ever undertaken for migraine prophylaxis) consistently found topiramate, at doses of 100 and 200 mg/day, to be superior to placebo in migraine prophylaxis. Topiramate has demonstrated efficacy in reducing the frequency of migraines, producing a statistically significant effect at 1 month and maintaining effectiveness over more than 6 months. It is not associated with the side effects that may cause…

Pharmacologic Approaches to CDH: Evidence and Outcomes

Chronic daily headache (CDH) is a highly prevalent condition that severely affects patient’s lives. Most patients with CDH experience chronic migraine (CM). The management of these patients is complex and includes acute and preventive pharmacological treatment. In CDH, the use of acute medication should be restricted to avoid the risk of medication-overuse headache. However, the use of preventive medication should be considered in all patients with CDH. There are few studies investigating the role of preventives in CDH, and the majority have CM. Topiramate and onabotulinumtoxinA are the only two drugs with proved scientific evidence in the prevention of CM. There are other neuromodulators, …

Almotriptan: meeting today’s needs in acute migraine treatment

Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigo…

Development and validation of the Migraine Screen Questionnaire (MS-Q).

Aim.—To develop and evaluate the clinimetric properties of a new migraine screening questionnaire: the Migraine Screen Questionnaire (MS-Q). Background.—Migraine is a public health problem requiring screening programs and tools to ensure early detection. Methods.—A questionnaire was developed based on the criteria of the International Headache Society (IHS) and a review of the literature by a committee of experts. Stage I: The original version of the MS-Q was distributed by mail and completed by Pfizer employees and self-administered to neurological patients; all subjects were afterward evaluated by a neurologist who was blinded to the MS-Q results, to establish an independent IHS diagnosis…

Time course of adverse events most commonly associated with topiramate for migraine prevention

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of …

The Global Campaign (GC) to Reduce the Burden of Headache Worldwide. The International Team for Specialist Education (ITSE)

The social perception of headache, everywhere at low levels in industrialised countries, becomes totally absent in developing ones. Headache disorders came into the World Health Organization’s strategic priorities after publication of the 2001 World Health Report. Among the leading causes of disability, migraine was ranked 19th for adults of both sexes together and 12th for females. The Global Campaign (GC) to Reduce the Burden of Headache Worldwide was planned by the major international headache organizations together with WHO in order to identify and remove those cultural, social and educational barriers recognised as responsible factors for the inadequate treatment of headache disorders …