Depression and anxiety in episodic and chronic cluster headache: a pilot study.

BACKGROUND: In contrast to migraine and tension-type headache, the psychiatric comorbidities of cluster headache (CH) have not been well-studied. OBJECTIVE: We assessed the presence of depression and anxiety in groups of episodic CH (ECH) and chronic CH (CCH) patients and compared CH patients with and without depression and anxiety. METHODS: Sociodemographics, comorbidities, and selected headache features were ascertained from a clinic-based sample in a cross-sectional fashion from January 2007 to July 2010. Active depression and anxiety were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7) scales. RESULTS: Of 49 CH patients, ECH patients (n=32) had an earlier age of onset and consumed less caffeine than CCH patients (n=17). Rates of depression as defined by a PHQ-9 score ≥10 were low in both ECH (6.3%) and in CCH (11.8%) with similar mean PHQ-9 scores (3.1 vs 3.7, P=.69). Rates of anxiety as defined by a GAD-7 score ≥10 were also low in both ECH (15.6%) and CCH (11.8%) with similar mean GAD-7 scores (3.8 vs 3.4, P=.76). ECH patients in and out of active attack periods had similar levels of depression and anxiety. Depression and anxiety usually occurred together in ECH and CCH patients. CH patients who were depressed or anxious were more likely to present at a younger age and have attack-related nausea and prodromal symptoms. Depressed CH patients were also more likely to have another pain disorder and had undertaken twice as many prophylactic medication trials. CONCLUSION: In this clinic-based cross-sectional study, ECH and CCH patients had similarly low rates of depression and anxiety. Rates were lower than those reported for both episodic and chronic migraine.

Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study.

OBJECTIVES: The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap-85mg sumatriptan and 500mg naproxen sodium), a butalbital-containing combination medication (BCM-50mg butalbital, 325mg acetaminophen, 40mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. BACKGROUND: Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy, butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital-containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication-overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. METHODS: Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2-24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double-blind, double-dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). RESULTS: A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test-6 of >59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28-29% of subjects took study medication within 15 minutes of migraine onset, 34-37% of subjects took study medication >15 minutes to 2 hours after onset, and 32-36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P≤.044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P≤.01); sustained pain relief 2-24 hours (P<.001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P≤.046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P≤.031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and <1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. CONCLUSIONS: This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.

Naming migraine and those who have it.

Medical language has implications for both public perception of and institutional responses to illness. A consensus panel of physicians, academics, advocates, and patients with diverse experiences and knowledge about migraine considered 3 questions: (1) What is migraine: an illness, disease, syndrome, condition, disorder, or susceptibility? (2) What ought we call someone with migraine? (3) What should we not call someone with migraine? Although consensus was not reached, the responses were summarized and analyzed quantitatively and qualitatively. Panelists participated in writing and editing the paper. The panelists agreed that "migraine," not "migraine headache," was generally preferable, that migraine met the dictionary definition for each candidate moniker, terms with psychiatric valence should be avoided, and "sufferer" should be avoided except in very limited circumstances. Overall, while there was no consensus, "disease" was the preferred term in the most situations, and illness the least preferred. Panelists disagreed strongly whether one ought to use the term "migraineur" at all or if "person with migraine" was preferable. Panelists drew upon a variety of principles when considering language choices, including the extent to which candidate monikers could be defended using biomedical evidence, the cultural meaning of the proposed term, and the context within which the term would be used. Panelists strove to balance the need for terms to describe the best science on migraine, with the desire to choose language that would emphasize the credibility of migraine. The wide range of symptoms of migraine and its diverse effects may require considerable elasticity of language.

Post-traumatic stress disorder, drug abuse and migraine: new findings from the National Comorbidity Survey Replication (NCS-R).

BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to be associated with migraine and drug abuse. METHODS: This was an analysis of data from the National Comorbidity Survey Replication (NCS-R) to evaluate the association of PTSD in those with episodic migraine (EM) and chronic daily headache (CDH). RESULTS: Our sample consisted of 5,692 participants. Lifetime and 12-month prevalence rates of PTSD were increased in those with EM and CDH. After adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11; women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the association between migraine with depression or anxiety. The lifetime OR of PTSD was also increased in CDH sufferers. The OR of illicit drug abuse was not increased in those with EM or CDH unless co-occurring with PTSD or depression. CONCLUSION: The lifetime and 12-month OR of PTSD is increased in those with migraine or CDH, and is greater in men than women with migraine. The lifetime and 12-month OR of illicit drug abuse is not increased in those with migraine or CDH unless co-occurring with PTSD or depression.

Headache attributed to psychiatric disorders.

The association between psychiatric illness and headache is widely recognized. "Headache attributed to psychiatric disorder" is a new category of secondary headache introduced in the 2004 revision of the International Classification of Headache Disorders (ICHD-II) (Headache Classification Subcommittee of the International Headache Society, 2004). It represents a new, but not conclusive, step toward a better systematization of the topic "headache and psychological factors." From the early 1990s the involvement of psychological factors in headache disorders has been clearly identified as "psychiatric comorbidity." The current conceptualization of the term implies an association, more than casual, but likely not causal, between an index disease or disorder and one or more coexisting physical or psychological pathologies. Additionally, clarifying the direction, meaning, and weight of comorbidities has pathophysiological, nosological, course, and treatment implications. However, the study of comorbidity may present a series of difficulties related to the current understanding of the etiology and pathophysiology of diseases at the center of our attention. Sometimes, as happens in the subject of headache, we proceed against a background where many issues need to be clarified. In this chapter, we analyze the past and current literature, tracing the line from "migraine personality" to "psychiatric comorbidity" to "headache attributed to psychiatric disorders." Questions related to etiology, pathophysiology, and treatment options are discussed for different headache subtypes.

Quantifying the return of headache in triptan-treated migraineurs: an observational study.

To improve understanding of secondary treatment failure in migraine patients, we evaluated 'headache return' as a novel endpoint to assess returning headaches according to their severity, expanding on current standard assessments of overall recurrence or relapse rates, in a six-month observational study of triptan-treated migraineurs. A total of 359 patients (91% female; mean age, 42.5 years) recorded data for 2168 headaches in electronic diaries. Two-thirds of headaches responded to triptan treatment (improved-to-mild or no pain two hours post-dose); 34% of headaches had a pain-free response. By 48 hours post-dose, 19% of all responding headaches returned; 24% of headaches achieving a pain-free response returned, predominantly to mild pain. More severe baseline headache, short duration since diagnosis of migraine, and female gender were associated with increased likelihood of headache return. Treatment satisfaction declined with increasing severity of headache return, demonstrating the value of assessing headache return by severity to fully evaluate its impact.

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.

Ten years of rizatriptan: from development to clinical science and future directions.

The year 2008 marked the 10th anniversary since rizatriptan was first launched for the acute treatment of migraine. In this article we discuss the concepts that motivated the preclinical and clinical development of rizatriptan, the clinical evidence that has driven its use over the past decade, rizatriptan's overall contribution to the field, and future directions for research.

Moving forward - essential questions for the next 10 years.

The future is bright for migraine sufferers. For acute treatment, CGRP antagonists and combination products will provide more complete, longer lasting, and safer relief. "Designer drugs" for migraine prevention will be identified based on their ability to block cortical spreading depression and will improve migraine treatment. Genetic and environmental risk factors that promote migraine progression will be identified and preventing progression will become a standard goal in treatment. Some of the devices intended to treat migraine will be approved and will provide important options for sufferers seeking to avoid drugs. Clinical trials that evaluate behavioral and pharmacologic interventions and their impact on patient centered outcomes will emerge. The emergence of novel treatments, when coupled with strategies for individualizing and optimizing treatment while maximizing adherence, will result in ever improving patient outcomes.

Development of a simple menstrual migraine screening tool for obstetric and gynecology clinics: the menstrual migraine assessment tool.

OBJECTIVE: To develop and validate a brief questionnaire to screen for menstrual migraine (MM), and to estimate MM prevalence in an obstetrics and gynecology (OB/GYN) setting in a pilot study. METHODS: Patients with unknown MM status from a headache clinic completed a 9-item questionnaire. The attributes of each question were compared with a validated headache calendar to develop a 3-item MM questionnaire. The headache calendar and questionnaire were then administered to nonpregnant/nonmenopausal OB/GYN patients. A diagnosis was assigned by a blinded specialist using the headache calendar, and MM prevalence was determined. RESULTS: The analysis yielded 3 relevant questions administered to 250 women for our tool, called the Menstrual Migraine Assessment Tool (MMAT): (1) "Do you have headaches that are related to your period (ie, occur between 2 days before the onset of your period, until the third day of your period) most months?" (2) "When my headaches are related to my period, they eventually become severe"; (3) "When my headaches are related to my period, light bothers me more than when I don't have a headache." If question 1 was positive, questions 2 and 3 were answered. Among women responding positively to question 1 and > or =1 other question, the sensitivity and specificity were 0.94 and 0.74, respectively. Of 610 randomly chosen OB/GYN patients, 12.1% had pure MM (ie, migraine exclusively between days +2 and -3 of menses), 10.1% had menstrually related migraine (ie, MM and attacks at other times), and 14.1% had migraine without relation to their menses. CONCLUSION: The MM screener MMAT exhibits sufficient sensitivity and specificity to assess this frequently disabling condition presenting at the OB/GYN office.

A randomized double-blind study comparing rizatriptan, dexamethasone, and the combination of both in the acute treatment of menstrually related migraine.

OBJECTIVES: To assess the efficacy and tolerability of rizatriptan (RI), dexamethasone (DE), and RI combined with DE (RI+DE) in the acute treatment of menstrually related migraine (MRM). METHODS: This was a randomized, double-blind, 6-attack crossover study comparing RI 10 mg, DE 4 mg, and RI+DE (2 attacks each). The primary endpoint was 24-hour sustained-relief. The secondary endpoint was 24-hour sustained pain-free. We treated the primary and secondary endpoint as dichotomous outcomes and used matched nonparametric statistics to assess proportions. We used logistic regression to determine the effect of treatment order and if response to previous treatment influenced treatment response. RESULTS: A total of 35 patients treated 190 attacks (mean of 5.4 per participant). For the primary endpoint, RI was significantly superior to DE (62.7% vs 33.3%, P = .001). RI+DE was superior to RI (81.5% vs 62.7%, P < .05) and to DE (81.5% vs 33.3%%, P < .001). For the secondary endpoint RI was also superior to DE (32.2% vs 12.1%, P < .05). RI+DE was superior to RI (50.7% vs 32.2%, P < .05) and DE (P < .01, RR). Similar findings were seen for the other endpoints. More attacks treated with DE+RI (33.8%) were associated with side effects, compared to RI (18.6%) and DE (15.2%). CONCLUSIONS: Rizatriptan is an effective treatment for MRM. RI+DE is significantly more effective than RI alone, although is associated with higher rate of adverse events.The combination should be considered for subjects with high disability, incomplete relief, or recurrence of pain with triptan monotherapy.The use of DE alone in the treatment ofMRMis not justified based on our data.

Memantine in the preventive treatment of refractory migraine.

OBJECTIVES: To assess the efficacy and tolerability of memantine(MEM)in the preventive treatment of refractory migraine. BACKGROUND: Glutamate is of importance in migraine pathophysiology and may be related to progression from episodic to chronic migraine. Furthermore, individuals with chronic pain often report cognitive problems. MEM has the potential to address both issues, justifying this pilot study. METHODS: We included subjects with refractory migraine (episodic migraine with 8-14 days of headache per month or transformed migraine, who had previously failed at least 2 trials of adequate preventive therapy). Other preventive drugs were allowed if the patient had been on a stable dose for more than 30 days. MEM dose ranged from 10 mg to 20 mg per day. The treatment phase lasted 3 months. The primary endpoint was number of days with headache at month 3. Cognitive performance was assessed with the trail making tests A and B (TMT-A and B). Statistical analyses were performed on the intent-to-treat (ITT) population, using data subjected to the last observation carried forward algorithm.We also conducted per protocol analyses. RESULTS: In the ITT population (n = 28), monthly headache frequency was reduced from 21.8 days at baseline to 16.1 (P < .01) at 3 months. The mean number of days with severe pain was reduced from 7.8 to 3.2 at 3 months (P < .01). The mean disability scores were significantly reduced at 3 months, compared with baseline (36.6 vs 54.9, P < .01). There was a significant reduction in the time to complete TMT-A at termination vs baseline (28.4 vs 23.2,P = .02) and also TMT-B (70.1 vs 50.4,P = .04). Side effects were present in 37.5% of the patients; 5.5% dropped out the study because of poor tolerability. Most adverse events were mild. CONCLUSION: This study offers preliminary evidence for the use of MEM in the prevention of refractory migraine.Double-blind studies are now required.

Healthcare provider-patient communication and migraine assessment: results of the American Migraine Communication Study, phase II.

OBJECTIVE: The American Migraine Communication Study I (AMCS I) revealed communication deficits illustrated by differing healthcare professional (HCP) and patient reports about issues such as impairment and frequency. AMCS II was designed to assess an intervention using open-ended questions about impairment and 'ask-tell-ask' sequences to confirm headache frequency in days versus attacks. RESEARCH DESIGN AND METHODS: HCPs who participated in AMCS I completed an internet-based intervention. Researchers were sent to HCPs' offices, and patients likely to discuss migraine were recruited immediately prior to normally-scheduled appointments. Post-consent, visits were recorded without a researcher present. Separate post-visit interviews were conducted with all parties. All interactions were transcribed. MAIN OUTCOME MEASURES: Transcripts were analyzed using validated sociolinguistic techniques, and study results were compared to AMCS I. RESULTS: HCPs assessed impairment in 90% of interactions compared to 10% in AMCS I (p<0.0001) and used open-ended questions to assess impairment in 55% of visits (95% CI: 0.4261-0.6598). Impairment between attacks was discussed in 37% of visits vs. 0% in AMCS I (p<0.0001). HCPs completed full ask-tell-ask sequences in 29% of visits (95% CI: 0.1921-0.4070). AMCS II contained more discussions of migraine preventive therapy with appropriate candidates compared to AMCS I (74 vs. 50%; p=0.069) without statistically increasing median visit length (9:36 vs. 11:00; p=0.668). Post-visit, HCPs and patients were often aligned about impairment and frequency and reported high levels of satisfaction. CONCLUSIONS: Although further research with a larger sample is needed, a brief, internet-based intervention appears to promote positive communication changes not associated with increased visit length.

Headache attributed to hypothyroidism.

Clinical and subclinical hypothyroidisms are common conditions in the population. Clinic-based studies suggest that hypothyroidism may be an exacerbating factor for some primary headaches. Furthermore, hypothyroidism may be a risk factor for incident new daily persistent headache. This article reviews the classification of the headaches attributed to hypothyroidism according to the second edition of the International Classification of Headache Disorders. We also review the prevalence, etiology, and principles of treatment of hypothyroidism. Because hypothyroidism is a treatable cause of secondary headaches, doctors should be aware of this relationship.

Harry Potter and the curse of headache.

Headache disorders are common in children and adolescents. Even young male Wizards are disabled by them. In this article we review Harry Potter's headaches as described in the biographical series by JK Rowling. Moreover, we attempt to classify them. Regrettably we are not privy to the Wizard system of classifying headache disorders and are therefore limited to the Muggle method, the International Classification of Headache Disorders, 2nd edition (ICHD-II). Harry's headaches are recurrent. Although conforming to a basic stereotype, and constant in location, throughout the 6 years of his adolescence so far described they have shown a tendency to progression. Later descriptions include a range of accompanying symptoms. Despite some quite unusual features, they meet all but one of the ICHD-II criteria for migraine, so allowing the diagnosis of 1.6 Probable migraine.

Efficacy of eletriptan in migraine-related functional impairment: functional and work productivity outcomes.

OBJECTIVE: To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7-item work productivity questionnaire (PQ-7), the functional assessment in migraine (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point global functional impairment scale (FIS). METHODS: Outpatients with an International Classification of Headache Disorders diagnosis of migraine were randomized to double-blind treatment of a single attack with either oral eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or placebo (n = 208). Patients were encouraged to take study medication as soon as they were sure they were experiencing a typical migraine headache, after the aura phase (if present) had ended. Patients with moderate-to-severe functional impairment were identified on each of the 4 disability scales, and 2-hour functional response was compared between treatments. RESULTS: At baseline, the PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring concentration, sustained work or attention, and ability to think quickly or spontaneously, were especially sensitive to the effects of mild headache pain, with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment. Only 11.3% of patients (n = 112) reported this level of impairment due to mild pain on the FIS. Functional response at 2 hours was significantly higher on eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001); on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n = 215; P= .017). These rates were all lower than the functional response rates on the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo (45%; P < .001). Conclusions.-In this exploratory analysis, use of multidimensional scales was found to provide a sensitive measure of headache-related functional impairment, especially for detecting clinically meaningful cognitive effects, and for detecting drug versus placebo differences.

Satisfaction with current migraine therapy: experience from 3 centers in US and Sweden.

OBJECTIVE: To assess the level of satisfaction and determinants of satisfaction or dissatisfaction of patients presenting in tertiary care, in regard to their usual care (UC) for the acute treatment of migraine. DESIGN/METHODS: Patients seen in 3 headache centers were assessed by means of 21 attributes related to their UC. Questions covered satisfaction with efficacy (including onset of relief, degree of relief, consistency of action, ease of use), tolerability (lack of side effects overall, CNS side effects, other side effects), and willingness to continue using the same medication and to change to another medication. All questions were answered on a 5-point scale (where 1 was strongly agree, 2 was agree, 3 was neutral, 4 was disagree, and 5 was strongly disagree). RESULTS: We assessed 183 subjects (74.8% women, mean age = 39.3 years). UC consisted, as a single drug or combination, of: triptan conventional tablets--62%; triptan disintegrating tablets--8%; sumatriptan nasal spray 9%; sumatriptan injection, 9%; nontriptans--19.6%. Most (54%) had no benefit within the first hour of treatment. The maximum benefit took more than 1 hour to be reached in 69%, and more than 2 hours in 36%. After the maximum benefit had been reached, pain worsened in 61%. Although 58% were satisfied with the degree of relief, 37% were dissatisfied with the speed of effect, 50% with the recurrence of pain, and 42% with the need for a second dose. Most were satisfied with the tolerability (56%). Finally, most (79.7%) said they were willing to try another acute medication. CONCLUSIONS: An important subset of patients, including a large subgroup of patients using triptans, is dissatisfied with their UC. Clinical trials assessing patients' preference should be conducted to complement the information from clinical trials.

Cluster headache treatment dilemmas: the experts respond.

When conventional treatment approaches to cluster headache are unsuccessful, expert recommendations are relevant but may not be easily accessible to treating clinicians. We conducted a study of expert recommendations in response to standardized vignettes. Ten expert headache clinicians were asked what treatment they would recommend for a hypothetical 55-year-old male cluster headache patient in the following five situations: 1) known coronary artery disease with response only to sumatriptan; 2) strictly unilateral headaches unresponsive to preventive treatment; 3) effective abortive treatment not covered by insurance; 4) patient request to obtain methysergide from Canada; and 5) headaches responsive only to steroid treatment.