Use Of Abortive Medications Research Articles

Filling the data gap on CGRP mAb therapy in low- to middle-income countries in Southeast Asia: insights from a real-world study in Thailand

BackgroundMost real-world data on CGRP mAbs have been published from high-income countries such as the USA, Western countries, Japan, Korea, and Singapore. However, data from low- and middle-income countries in Southeast Asia is lacking. This is the first real-world study from Thailand to describe the efficacy of CGRP mAbs therapy in migraine patients and to analyze the response trends between episodic migraine and chronic migraine.MethodsWe conducted a single-center, real-world retrospective chart review study with an observation period of 6 months after CGRP mAbs initiation. We aim to compare treatment responses to CGRP mAbs between EM and CM patients.ResultsA total of 47 Thai patients were enrolled (median [IQR] age 37.2 [28.6–50.4] years; 85.1%F, 44.7% EM; 70.2% galcanezumab). There was no difference in baseline characteristics and migraine disability assessment (MIDAS) between EM and CM. The overall ≥ 30%, ≥ 50%, and ≥ 70% monthly migraine day reduction rates at 6 months were 89.0%, 71.6%, and 58.5% with higher responders in EM. There was a significant decrease in monthly headache days (MHDs) over time (adjusted β = -0.42, p < 0.001) and a significant decrease in MIDAS score over time after the initiation of CGRP mAbs (adjusted β = -1.12, p = 0.003). However, there were no differences between the two diagnoses. There was no significant decrease in the number of abortive medication pills used over time after the initiation of CGRP mAbs. CM had a significantly steeper trend compared to those with EM.ConclusionThe first real-world study in Thailand demonstrated that CGRP mAbs therapy had efficacy for migraine treatment, as evidenced by a reduction in MHDs, decreased disability, and reduced use of abortive medications. Additionally, the response pattern to CGRP mAbs therapy was similar between EM and CM in terms of MHDs reduction and MIDAS score improvement.

The impact of updates in headache quality measures on adherence to best practices in a neurology resident clinic: A quality improvement study

AbstractObjectiveTo apply the 2019 joint American Academy of Neurology (AAN) and American Headache Society (AHS) quality measures for headache management to a cohort of neurology resident physicians and then assess outcomes related to guideline adherence.BackgroundThe optimization of headache management is essential to reduce both the individual and systemic impact of these disorders. In 2014, the AAN developed 10 quality measures for evidence‐based management of patients with headache. A workgroup updated and condensed its headache quality measures in 2019, narrowing the set to six measurements, four of which would primarily focus on the management of migraine and two of which would address the management of cluster headache.MethodsThis quality improvement study was conducted using a pretest‐posttest study design. A pre‐intervention survey based on retrospective analysis of five clinic notes for adherence to the measures was designed and distributed to all neurology residents (n = 32) at a large, academic tertiary referral center. The intervention included the creation of an electronic medical record template to aid residents in following the measures during clinical encounters, as well as the provision of direct feedback based on pre‐intervention results. Finally, a post‐intervention survey was distributed for completion based on notes written during the intervention period. Analysis was limited to migraine, given the low percentage of cluster headache seen in clinic.ResultsAn increase in adherence was seen in three of the four migraine‐related quality measures, with the Use of Abortive Medications for Migraine and Documentation of Counseling on Modifiable Lifestyle and Chronification Factors demonstrating statistically significant improvements (75.8% to 88.0% [p = 0.013] and 83.9% to 94.0% [p = 0.029] adherence, respectively). For secondary outcomes, the increase in the utilization of appropriate diagnostic criteria (82.6% to 93.2%, p = 0.018) was significant, and the self‐assessed confidence rating for adherence to guidelines was significant (p &lt; 0.001).ConclusionsThis study provides evidence that the quality improvement intervention led to increased adherence to the AAN and AHS migraine‐related measures. It is anticipated that increased adherence may lead to improved patient outcomes.

Patterns of anti-CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy.

To describe the pattern of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) utilization in the Tuscany region, Italy, and the variation of triptan consumption after treatment initiation. Given the recent commercialization of anti-CGRP mAbs as migraine preventive medications, real-world evidence on their patterns of utilization and their impact on migraine abortive medication use is still limited. A retrospective, descriptive, cohort study on the real-world utilization of anti-CGRP mAbs was performed using the population-based regional administrative database of Tuscany. Patients with ≥1 anti-CGRP mAb dispensing (namely erenumab, galcanezumab, fremanezumab) between April 1, 2019, and September 30, 2021, were identified. The first dispensing was the cohort entry (CE). New users (NUs) were patients with no anti-CGRP mAb dispensing before CE. Kaplan-Meier (KM) curves were plotted to describe the cumulative probability of remaining with the initial anti-CGRP mAb during a 15-month follow-up period as a measure of treatment persistence. Among NUs with ≥2 triptan dispensings during the 6 months before CE (i.e., baseline), the mean monthly number of triptan dosage units dispensed was measured in five consecutive follow-up time windows (months 1-3, 4-6, 7-9, 10-12, 13-15) and the difference from the baseline was calculated. A total of 624 NUs (erenumab = 295, galcanezumab = 223, fremanezumab = 106) were identified, of whom 188 (78%) were women. Mean age was 49.2 years (standard deviation [SD] = 12.6). The survival to discontinuation at 6, 12, and 15 months was about 69%, 48%, and 6%, respectively. The survival to switch was about 6% at 15 months. The observed variation of triptan consumption at 3/6/9/12/15 months and the corresponding SD was -4.4 [8.2]/-5.2 [9.0]/-5.5 [9.2]/-5.4 [9.2]/-4.5 [10.0], respectively. Patient demographics reflect the place of these medications in therapy. Overall, findings seem to indicate a favorable tolerability and effectiveness profile. Further studies are warranted to better establish the long-term comparative effectiveness, safety, and cost effectiveness of anti-CGRP mAbs compared to other preventive medications.

Combined Prophylaxis of Chronic Migraine with OnabotulinumtoxinA and Anti-CGRP Antibodies

Objective: To evaluate the efficacy of adding large molecule anti-calcitonin gene-related peptide monoclonal antibodies (mAbs) to onabotulinumtoxinA (OBT-A) for chronic migraine prevention. Background: Chronic migraine (CM) is a highly prevalent, debilitating disorder that leads to personal, social, and economic burdens. Both OBT-A and mAbs are proven safe and effective in chronic migraine prevention. The use of combination therapy has not been formally studied but may prove more effective than either monotherapy alone in select patients. Methods: This is a retrospective chart review of patients with chronic migraine, treated with OBT-A, who received additional mAb preventative therapy. The primary endpoint was migraine headache days per month (MHD) after 3 months of combined therapy. Secondary endpoints included total headache days per month, headache intensity, disability level, and use of abortive medications. Results: Of 1503 patients reviewed, 133 met inclusion criteria. At 3 months of combined therapy, mean reduction of MHD from baseline was 6.2 (95% CI 4.91 to 7.49, p &lt; 0.0001). Nearly 2/3rd of patients (60.9%) experienced ≥ 50% MHD reduction. Fewer patients reported high disability level (14.6% [17/126], compared to 29.4%) and high headache intensity (13.0% [16/119], compared to 51.3%) at 3 months (all p &lt; 0.0001). A reduction in abortive medication doses needed and discontinuation of concomitant oral preventative medications was also noted in 15.8% and 6.8% of patients, respectively. Conclusions: Combined therapy with OBT-A and mAbs is well-tolerated, effective in further reducing migraine frequency, and may improve quality of life for patients with CM refractory to monotherapy.

Clinic and genetic predictors in response to erenumab.

Background and purposeErenumab (ERE) is the first anticalcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.MethodsProspective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio‐demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine‐related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test‐6), and use of abortive medications, during 3 months before and after ERE start were collected. Real‐time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor‐like receptor and receptor activity‐modifying protein‐1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50‐RESP) and 75% responder patients (75‐RESP).ResultsAt month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50‐RESP, and 30/110 (27.3%) were 75‐RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008–1.120], p = 0.024), number of failed preventive medications (0.753 [0.600–0.946], p = 0.015), and MIDAS score (1.011 [1.002–1.020], p = 0.017) were associated with 75‐RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75‐RESP (per G allele OR [95% CI]: 0.53 [0.29–0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28–1.10], p = 0.09]).ConclusionsIn this real‐word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.

The Vitamin D Role in Preventing Primary Headache in Adult and Pediatric Population.

Headache is among the main neurological disorders with a great impact on both adults and children. The diagnosis of primary headache and proper management is often delayed with a great impact on work productivity and overall quality of life. Chronic headache often requires prophylactic therapy to reduce the frequency and severity of the attacks and the use of abortive medications. Besides the use of several classes of drugs, another treatment modality is the use of Nutraceuticals. Some studies have suggested a possible role of vitamin D in headache prophylaxis. Indeed, vitamin D is involved in several pathways of brain development, neuroprotection and neurotransmission. Moreover, there is data suggesting a close relationship between primary headache and vitamin D deficiency, both in children and in adults. To date, a few studies have evaluated the effect of vitamin D on headaches. The aim of this review is to summarize the data collected on headache prophylaxis with vitamin D comparing the effects of vitamin D in pediatric and adult populations.

The impact of Pain-related emotions on migraine

The response to pain is highly individual and can be influenced by complex emotional perception. This study aims to investigate the status of the pain-related emotional response, and the influence on headache characteristics and disability in migraine. We studied the pain-related emotional response in 145 consecutive migraine patients using the Pain Anxiety Symptoms Scale (PASS), the Pain Catastrophizing Scale (PCS), and the Pain Sensitivity Questionnaire (PSQ) and compared them with 106 healthy controls. We investigated the relationship between emotional factors and migraine characteristics. The effect of pain-related emotion on migraine-related disability assessed with the Headache Impact Test-6 (HIT-6) and the Migraine Disability Assessment (MIDAS). Migraine patients showed significantly higher scores on total PASS (p < 0.001), PCS (p < 0.001) and PSQ (p = 0.002) compared to the healthy controls. The HIT-6 was weakly correlated with PASS (r = 0.390, p < 0.001) and PCS (r = 0.354, p < 0.001). PASS-Total (p = 0.001), headache frequency (p = 0.003), and HADS-Anxiety (p = 0.028) were independent variables associated with HIT-6. Headache frequency (p < 0.001) was an independent variable associated with MIDAS. The structural equation model indicated that headache severity has direct loading on emotion and subsequently influenced migraine-related disability. Disability has a significant effect on the frequency of abortive medication use. Migraine patients have altered emotional responses to pain perception. Pain-related anxiety made an important contribution to headache-related disability. The present results suggest that the management of disability by considering various pain-related emotional factors may be necessary for the therapeutic aspects of migraine.

OnabotulinumtoxinA Wear-off Phenomenon in the Treatment of Chronic Migraine.

To evaluate the frequency and features of onabotulinumtoxinA (onabotA) wear-off in chronic migraine (CM). Clinical experience suggests that patients with CM frequently perceive onabotA treatment duration <12weeks, but this phenomenon has not been well explored. This study was a retrospective chart review of patients (n = 143) with CM initiated on onabotA over a 2-year period. Wear-off was considered present with the phrase documented, a quantitative headache day increase, or increased use of abortive medications, bridging therapies or emergency department visits in the 6weeks preceding the subsequent administration. Wear-off was present in 90/143 patients (62.9%). Age, sex, medication overuse, psychiatric comorbidity, injector training level, and mean days between injections did not differ between the wear-off and no wear-off groups. Mean units injected per session in the wear-off group until first documented wear-off were significantly less vs no wear-off group (166.0±13.1 vs 173.4±10.3, P=.0005). Wear-off most commonly occurred 2-4weeks before the next injection (43.3%) and after the very first injection (40.0%). Intramuscular ketorolac injections (33.3%) and peripheral nerve blocks (25.6%) were the most common bridge therapies used in the wear-off period. Most patients with CM receiving onabotA experience wear-off. Clinicians may consider increasing the units used from the treatment onset to reduce the frequent need for bridging therapies.

Transcranial Magnetic and Direct Current Stimulation (TMS/tDCS) for the Treatment of Headache: A Systematic Review.

Headache is among the most prevalent causes of disability worldwide. Non-pharmacologic interventions, including neuromodulation therapies, have been proposed in patients who are treatment resistant or intolerant to medications. To perform a systematic review on the use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for the treatment of specific headache disorders (ie, migraine, tension, cluster, posttraumatic). Data sources: Ovid MEDLINE, Cochrane Central Register of Clinical Trials, Embase, Scopus, PsycINFO. All references were reviewed by 2 independent researchers (3039 abstracts, duplicates removed). Records were selected by inclusion criteria for participants (adults 18-65 with primary or secondary headaches), interventions (TMS and tDCS applied as headache treatment), comparators (sham or alternative standard of care), and study type (cohort, case-control, and randomized controlled trials [RCT]). Studies were assessed using the Cochrane Risk of Bias Tool and overall quality determined through the GRADE Tool. A structured synthesis was performed due to heterogeneity of participants and methods. Thirty-four studies were included: 16 rTMS, 6 TMS (excluding rTMS), and 12 tDCS. The majority investigated treatment for migraine (19/22 TMS, 8/12 tDCS). Quality of evidence ranged from very low to high. Of all TMS and tDCS modalities, rTMS is most promising with moderate evidence that it contributes to reductions in headache frequency, duration, intensity, abortive medication use, depression, and functional impairment. However, only few studies reported changes greater than sham treatment. Further high-quality RCTs with standardized protocols are required for each specific headache disorder to validate a treatment effect. Registration Number: PROSPERO 2017 CRD42017076232.

OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective multicentre descriptive study.

OnabotulinumtoxinA is a treatment specifically approved for the prophylaxis of chronic migraine in adults. The aim of this study was to assess the effectiveness of OnabotulinumtoxinA in chronic migraine after 1 year of treatment in a real-life setting and to identify clinical predictors of outcome. We designed a prospective multicentre study performed in 13 hospitals in Spain. Patients underwent a complete medical history and examination. They were treated with OnabotulinumtoxinA every 12 weeks for 1 year. Data about outcome, adverse events, abortive medication use, emergency room use and disability were collected at 3 and 12 months. A total of 725 subjects completed the study. At 12 months, 79.3% showed >50% reduction in number of headaches per month and 94.9% reported no adverse events. Unilaterality of pain, fewer days of disability per month and milder headache at baseline were correlated with good outcome. Duration of disease <12 months increased the chances of response to treatment with OnabotulinumtoxinA (odds ratio, 1.470; 95% confidence interval, 1.123-2.174; P = 0.045). This study confirmed the effectiveness of treatment with OnabotulinumtoxinA after 1 year of treatment. The chances of a good outcome may be increased by starting treatment in the first 12 months after chronic migraine diagnosis.

Fatores maternos para o nascimento de recém-nascidos com baixo peso e prematuros: estudo caso-controle

Objective: To identify maternal factors most associated with the birth of low weight and premature infants. Materials and Methods: Case-control study with 111 mothers who sought care at a public hospital in Feira de Santana (BA). The case group consisted of mothers of newborns with low birth weight (<2500g) and <37 weeks; and the control group of mothers of newborns with normal weight (≥2500g) and term. Birth weight and gestational age were obtained from hospital records. The main risk factors for low birth weight and prematurity were assessed by bivariate analysis and by calculating the odds ratio (OR). Results: 18.9% of mothers had preterm deliveries and, in 38.1% of cases, delivered before 34 weeks. Most of these women were aged between 14 and 25 years (66.7%), black or mulatto (85.7%), had a partner (81.0%), vaginal delivery (57.0%) and visited dentist during pregnancy (95.2%). There was a statistically significant association between low birth weight/premature delivery and consumption of alcoholic beverages (OR: 7.9; p=0.001), number of antenatal visits less than 6 (OR: 2.94; p=0.02) and the use of abortive medication (OR: 5.05; p=0.04). Conclusion: The findings showed that women who consumed alcohol, had fewer than six prenatal consultations and used abortive medication, had a greater chance of delivering a baby with low birth weight and premature. Thus, these risk factors deserve special attention in public policies to face this disease.

Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache.

BackgroundCluster headache (CH) is a debilitating condition that is generally associated with substantial health care costs. Few therapies are approved for abortive or prophylactic treatment. Results from the prospective, randomised, open-label PREVA study suggested that adjunctive treatment with a novel non-invasive vagus nerve stimulation (nVNS) device led to decreased attack frequency and abortive medication use in patients with chronic CH (cCH). Herein, we evaluate whether nVNS is cost-effective compared with the current standard of care (SoC) for cCH.MethodsA pharmacoeconomic model from the German statutory health insurance perspective was developed to estimate the 1-year cost-effectiveness of nVNS + SoC (versus SoC alone) using data from PREVA. Short-term treatment response data were taken from the clinical trial; longer-term response was modelled under scenarios of response maintenance, constant rate of response loss, and diminishing rate of response loss. Health-related quality of life was estimated by modelling EQ-5D™ data from PREVA; benefits were defined as quality-adjusted life-years (QALY). Abortive medication use data from PREVA, along with costs for the nVNS device and abortive therapies (i.e. intranasal zolmitriptan, subcutaneous sumatriptan, and inhaled oxygen), were used to assess health care costs in the German setting.ResultsThe analysis resulted in mean expected yearly costs of €7096.69 for nVNS + SoC and €7511.35 for SoC alone and mean QALY of 0.607 for nVNS + SoC and 0.522 for SoC alone, suggesting that nVNS generates greater health benefits for lower overall cost. Abortive medication costs were 23 % lower with nVNS + SoC than with SoC alone. In the alternative scenarios (i.e. constant rate of response loss and diminishing rate of response loss), nVNS + SoC was more effective and cost saving than SoC alone.ConclusionsIn all scenarios modelled from a German perspective, nVNS was cost-effective compared with current SoC, which suggests that adjunctive nVNS therapy provides economic benefits in the treatment of cCH. Notably, the current analysis included only costs associated with abortive treatments. Treatment with nVNS will likely promote further economic benefit when other potential sources of cost savings (e.g. reduced frequency of clinic visits) are considered.Trial registrationClinicaltrials.gov identifier NCT01701245, 03OCT2012.

Analysis of nortriptyline's prophylaxis on hemodialysis headache patients - a pilot study

Background: Headache is the most common neurological symptom of patients on hemodialysis treatment. However, this condition is usually treated only after the pain has already begun. Objective: Determine the efficacy and tolerability of nortriptyline as a prophylactic treatment for patients diagnosed with hemodialysis headache. Methods: This study is an open and a prospective clinical trial. Twelve patients with hemodialysis headache were studied in this trial. They were asked to take nortriptyline (25 mg per day) during three months as a prophylaxis for their headaches. Weekly interviews were made to register eventual headaches. Additionally, other clinical features were analyzed such as the intensity of pain, its location, side effects of the drug and use of abortive medications. Results: There was a significant reduction (p &lt; 0.05) in the intensity as well as frequency of pain. The duration of the episodes also decreased. Conclusions: Our findings suggest that nortriptyline 25 mg is capable of reducing not only the frequency, but also the intensity of the pain in the hemodialysis headache. However, further studies are necessary.

Medication-overuse headache: an update.

Medication-overuse headache (MOH) is a chronic daily headache evolving from an episodic primary headache (mainly migraine) due to overuse of one or more classes of migraine abortive medication. The development of MOH is associated with both overuse of one or more medication and behavioral predispositions. MOH causes a significant decline in the quality of life and reduces functioning in patients affected. In the same MOH patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. In a recent study of our group, we found that MOH patients had a more complex profile of psychiatric comorbidity compared to episodic migraine (EM) patients. Furthermore, clinically relevant obsessive-compulsive disturbances for abused drugs assessed by Yale-Brown Obsessive Compulsive Scale Y-BOCS, appeared to be more represented in the MOH group, while the prevalence of this trait in the EM group was comparable to that of healthy controls (unpublished results). Management of MOH represents a difficult challenge for clinicians and headache experts, particularly because of the high percentage of relapse after a successful withdrawal treatment. This can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy and use of abortive medication with minimal risk of MOH, avoiding previously overused medications. With the aim to verify the efficacy and safety of sodium valproate in the short-term treatment of MOH, we recently carried out a multicentre study (SAMOHA study) which demonstrated a superiority of the drug compared to placebo after detoxification[1]. In an ancillary study of SAMOHA, analysing responders and non responders to detoxification and advice to withdraw a benefit was excluded in patients with a long history of MOH[2]. In a further ancillary research we found a significant correlation between MOH relapse and the total MSQ score, the Role Preventive and the Emotional Function sub-scales, suggesting a poorer quality of life in non responders[3]. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse. In a recent study of our group involving a subsample of MOH patients enrolled in the SAMOHA study, we sequenced all exons, intron/exon junctions and 3'-5'UTR regions of HDAC3 gene which had been implicated in excessive medication consumption in MOH patients. Univariate analysis showed that the G allele of the exonic SNP rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which acute medication were used (unpublished results).

Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.

BackgroundChronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH.MethodsPREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed.ResultsDuring the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred.ConclusionAdjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.

Clinical Aspects of Medication Overuse Headaches

Medication overuse headache (MOH) is a subset of chronic daily headache, occurring from overuse of 1 or more classes of migraine abortive medication. Acetaminophen, combination analgesics (caffeine combinations), opioids, barbiturates (butalbital), non-steroidal anti-inflammatory drugs, and triptans are the main classes of drugs implicated in the genesis of MOH. Migraine seems to be the most common diagnosis leading to MOH. The development of MOH is associated with both frequency of use of medication and behavioral predispositions. MOH is not a unitary concept. The distinction between simple (type 1) vs complex (type 2) forms is based on both the class of overused medication and behavioral factors, including psychopathology and psychological drug dependence. MOH is a challenging disorder causing decline in the quality of life and causing physical symptoms, such as daily and incapacitating headaches, insomnia, and non-restorative sleep, as well as psychological distress and reduced functioning. MOH is associated with biochemical, structural, and functional brain changes. Relapse after detoxification is a challenge, but can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding previously overused medication, and providing psychological (cognitive-behavioral) therapy.

Hemicrania Continua Should NOT Be Classified as a Trigeminal Autonomic Cephalalgia

The pain of the so-called functional or primary headache disorders, such as tension headache, migraine, or cluster headache, can be associated with autonomic symptoms that are localized in nature. The localized autonomic symptoms probably involve higher centers of autonomic regulation, for example the hypothalamus, for which there is support from functional magnetic resonance imaging studies. Hemicrania continua, a continuous, unilateral, side-locked headache, absolutely responsive to preventive treatment with indomethacin, is contrasted with so-called medication-overuse headache, in which the paradoxical situation exists of tremendous suffering despite excessive use of abortive medications. In classification, clinical presentation trumps experimental testing: Not only is there no basis to classify hemicrania continua in the category of the so-called trigeminal autonomic cephalalgias, also the very existence of this category lacks solid foundation.

P02.55. Craniosacral therapy for migraine: a feasibility study

Methods Individuals with moderate to severe migraine were recruited from specialty clinics, family practices, and the university community. After confirmatory clinical evaluation and an 8-week run-in phase, those meeting study criteria (compliant with study procedures, at least 5 migraines per month) were randomized to 8 weekly CST or low-strength static magnet therapy (LSSM) treatments. Study participants were followed for 4 weeks after the conclusion of therapy. Primary outcome measures included headache frequency and headache-specific quality of life (HIT-6). Secondary headache-specific measures include headache-related disability (MIDAS), headache intensity, and abortive medication use.

Cost Effectiveness of Pharmacotherapy for the Prevention of Migraine

There are few data about the cost effectiveness of prophylactic medications for migraine. Clinical trials have shown several preventive agents to be useful in reducing the frequency of migraine attack while having tolerable side effects. To compare the cost effectiveness of adding preventive treatment to abortive therapy for acute migraine with abortive therapy for acute migraine alone in the primary care setting. A Markov decision analytic model with a cycle length of 1 day, a time horizon of 365 days and three health states was used to perform an analysis comparing the cost effectiveness and utility of five treatments for migraine prophylaxis (amitriptyline 75 mg/day, topiramate 100 and 200 mg/day, timolol 20 mg/day, divalproex sodium 1000 mg/day or propranolol 160 mg/day) with treatment of acute migraine alone for the management of migraine in the primary care setting. One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. The expected total annual cost for the use of preventive agents ranged from $US2932 to $US3887, compared with $US3960 for the use of abortive medications only. In the baseline analysis, use of each of the five preventive agents generated more quality-adjusted life-years (QALYs) and incurred lower costs compared with abortive medications only. Monte Carlo Simulation suggested that amitriptyline 75 mg/day was most likely to be considered a cost-effective option versus the other five therapies, followed by timolol 20 mg/day, topiramate 200 mg/day, topiramate 100 mg/day, divalproex sodium 1000 mg/day and propranolol 160 mg/day when the willingness-to-pay (WTP) for society is <$US18 000 per QALY gained. Preventive medications appear to be a cost-effective approach to the management of migraine in the primary care setting compared with the approach of abortive treatment only. Among those preventive agents, probabilistic sensitivity analysis suggests that, when the societal WTP is <$US18 000 per QALY gained, amitriptyline 75 mg/day is most likely to be considered a cost-effective option.

Topiramate versus amitriptyline in migraine prevention: A 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs

Objective: The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache. Methods: This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment. Results: The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ ( P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction ( P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in ±5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%). Conclusions: In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.