Real-world experience with once-daily gabapentin for the treatment of postherpetic neuralgia (PHN).

OBJECTIVES: To evaluate the safety and effectiveness of once-daily gastroretentive gabapentin (G-GR) for the treatment of postherpetic neuralgia in real-world clinical practice. MATERIALS AND METHODS: Patients aged 18 years and above were divided into 2 cohorts: patients aged 70 years and below and patients above 70 years. All patients were titrated to 1800 mg G-GR/d over 2 weeks and maintained at that dosage for 6 weeks, for 8 weeks total treatment. To reflect clinical practice, exclusion criteria were limited to those in the product label. Efficacy was assessed using a visual analog scale (VAS) and the Brief Pain Inventory. Patient/Clinician Global Impression of Change scales were completed at week 8. Adverse events (AEs) were assessed. RESULTS: The efficacy population included 190 patients (110, 70 y and below; 80, above 70 y). The mean percent change in VAS score at week 8 from baseline was -21.3%/-20.4% (70 y and below/above 70 y). The proportion of patients with a ≥30% reduction in VAS score from baseline was 51.8%/55.0% (70 y and below/above 70 y) and was 42.7%/37.5% for a ≥50% reduction. Brief Pain Inventory scores were all significantly reduced by week 8. On the Patient Global Impression of Change instrument, more patients aged 70 years and below reported feeling "much" or "very much" improved from baseline (59.0% vs. 40.3%). G-GR was generally well tolerated. Thirty-seven (18.8%) patients experienced AEs that led to discontinuation. No patients died and 5 (2.5%) patients experienced serious AEs. The most common G-GR-related AEs (70 y and below/above 70 y) were dizziness (11.7%/16.3%) and somnolence (3.6%/8.1%). DISCUSSION: In real-world clinical practice, G-GR seems to be an effective, well-tolerated treatment option for patients with postherpetic neuralgia, regardless of age.

New daily persistent headache and potential new therapeutic agents.

New daily persistent headache is a form of a chronic daily headache with a unique temporal profile. Patients can recall the exact day when their headache started. It can be one of the most refractory types of headache to treat. Recent publications have highlighted different subtypes and heterogeneity in presentation. Referring to it as a syndrome versus a distinct disorder has also been suggested. Several different classes of medications have been used for the treatment, with mixed results. The underlying pathophysiology of new daily persistent headache is unclear, but tumor necrosis factor may play a role. The clinical features, differential diagnosis and potential new therapeutic agents will be discussed.

CoEnzyme Q10 and riboflavin: the mitochondrial connection.

OBJECTIVE: We conducted a short review of relevant literature which contends that migraine is associated with a wide-spread metabolic abnormality of mitochondrial oxidative metabolism, leading to the use of riboflavin and coenzyme Q10 as prophylactic therapy for migraine. BACKGROUND: Riboflavin and coenzyme Q10 supplementation has been recommended widely as safe and effective prophylactic therapy for migraine. The background neurophysiological studies that led to the development of this therapy, which are extremely complex, deserve wider distribution. METHODS: A brief review of the relevant literature was conducted and summarized. RESULTS: Brain energy metabolism in migraine has been found to be abnormal in all types of migraine, making the migrainous brain hyper-responsive to many stimuli. The metabolic abnormalities are more severe in the more-severe types of migraine, such as hemiplegic migraine and migrainous stroke, but they are present both during and between attacks. The metabolic abnormality in migraine extends beyond the brain to platelets and muscles, as proven by techniques of biochemistry, muscle morphology, and nuclear magnetic spectroscopy. There are strong similarities between migraine and certain inborn errors of metabolism, the metabolic encephalomyopathies, in which patients suffer genetic abnormalities in mitochondrial energy production to produce lactic acidosis, stroke, and migraine headaches. The theory of migraine as a mitochondrial disorder seems to have abundant evidence. However, aside from the genetic abnormalities discovered for the familial hemiplegic migraines, molecular genetic studies in migraine have been negative until recently, when whole genome sequencing has now reported positive results. CONCLUSION: Arising from these extensive neurophysiological studies, the treatment of metabolic encephalomyopathies with pharmacological doses of riboflavin and coenzyme Q10 has shown positive benefits. The same treatment has now been applied to migraine, adding clinical support to the theory that migraine is a mitochondrial disorder.

Defining refractory migraine: results of the RHSIS Survey of American Headache Society members.

OBJECTIVES: To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. BACKGROUND: Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. DESIGN: A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. RESULTS: American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. CONCLUSIONS: There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.

Defining refractory migraine and refractory chronic migraine: proposed criteria from the Refractory Headache Special Interest Section of the American Headache Society.

Certain migraines are labeled as refractory, but the entity lacks a well-accepted operational definition. This article summarizes the results of a survey sent to American Headache Society members to evaluate interest in a definition for RM and what were considered necessary criteria. Review of the literature, collaborative discussions and results of the survey contributed to the proposed definition for RM. We also comment on our considerations in formulating the criteria and any issues in making the criteria operational. For the proposed definition for RM and refractory chronic migraine, patients must meet the International Classification of Headache Disorders, Second Edition criteria for migraine or chronic migraine, respectively. Headaches need to cause significant interference with function or quality of life despite modification of triggers, lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The definition requires that patients fail adequate trials of preventive medicines, alone or in combination, from at least 2 of 4 drug classes including: beta-blockers, anticonvulsants, tricyclics, and calcium channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE) intranasal or injectable formulation and either nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesic, unless contraindicated. An adequate trial is defined as a period of time during which an appropriate dose of medication is administered, typically at least 2 months at optimal or maximum-tolerated dose, unless terminated early due to adverse effects. The definition also employs modifiers for the presence or absence of medication overuse, and with or without significant disability.

Cluster headache: myths and the evidence.

Although cluster headache (CH) has been the focus of a great deal of research, it also has been the focus of a great deal of speculations that have been repeated commonly as fact. The authors conducted a thorough review of the literature and an informal poll of several noted headache experts to investigate the truth behind common myths and hypotheses regarding CH. They then present an overview of some of these more common hypotheses, observations, and myths, and offer a brief review of the existing evidence supporting or negating the theories. These include gender, genetics, suicidality, homicidality, physical appearance, personality, and psychologic features of the patient with CH.

Topical agents in the treatment of cluster headache.

This article discusses topical intranasal medications in the treatment of cluster headache.