Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study.

Background: Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks. Objective: We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH). Methods: A cross-sectional, prospective, randomized, open study with real-world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs. Results: A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001). Conclusions: The addition of an anti-CGRP monoclonal antibody to the treatment for medication overuse headaches in chronic migraineurs may result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs.

Indomethacin for refractory COVID or post-COVID headache: a retrospective study.

BACKGROUND: COVID-19, a disease caused by SARS-CoV-2, manifests with headache, both in the acute phase and as a post-infection symptom, which may be refractory to usual analgesics. OBJECTIVES: Investigate the therapeutic response of refractory COVID or post-COVID headache to indomethacin. METHODS: This was an observational, retrospective, open and uncontrolled. A sample of 37 patients diagnosed with COVID-19 presenting headache during the acute phase or after the resolution of the disease, with refractoriness to the usual symptomatic medication was treated with indomethacin. RESULTS: Of the 37 patients (24 women and 13 men), 29 were migraineurs and 8 had no previous history of headache. The average age was 40.4 ± 9.4 years, ranging from 19 to 65 years. In 26 (70.3%) patients, the onset of headache occurred within 72 h, and in 11 (29.7%), after 10 days of positivity for Sars-CoV-2. After treatment with indomethacin, 36 patients reported greater than 50% headache relief from the third day and 5 became asymptomatic on the fifth day. CONCLUSIONS: In patients with migraine or no prior history of headache who present with refractory COVID or post-COVID headache to common analgesics, anti-inflammatory drugs, and/or triptans, indomethacin should be considered a therapeutic option.

Migraine: epidemiology and systems of care.

Migraine is a neurovascular disorder that affects over 1 billion people worldwide. Its widespread prevalence, and associated disability, have a range of negative and substantial effects not only on those immediately affected but also on their families, colleagues, employers, and society. To reduce this global burden, concerted efforts are needed to implement and improve migraine care that is supported by informed health-care policies. In this Series paper, we summarise the data on migraine epidemiology, including estimates of its very considerable burden on the global economy. First, we present the challenges that continue to obstruct provision of adequate care worldwide. Second, we outline the advantages of integrated and coordinated systems of care, in which primary and specialist care complement and support each other; the use of comprehensive referral and linkage protocols should enable continuity of care between these systems levels. Finally, we describe challenges in low and middle-income countries, including countries with poor public health education, inadequate access to medication, and insufficient formal education and training of health-care professionals resulting in misdiagnosis, mismanagement, and wastage of resources.

Medication overuse headache: an overview of clinical aspects, mechanisms, and treatments.

INTRODUCTION: Medication-overuse headache (MOH) is a common debilitating neurological disorder, with a prevalence of 1% to 7% in general population. It affects more than 60 million people worldwide and provokes substantial burden. Despite that, most practitioners don't know MOH. This review aims at presenting MOH clinical features, pathophysiology insights, and recent knowledge and guidance regarding treatments. AREAS COVERED: A literature search in the major medical databases including the terms 'medication overuse headache,' 'chronic daily headache,' 'chronic migraine,' 'symptomatic medication overuse' and others, published between 1990 and 2020, was carried out. EXPERT COMMENTARY: Primary headache sufferers such as migraineurs and tension-type headache patients may increase the headache frequency and induce the transition from episodic to chronic forms, as well as develop MOH, in the presence of medication overuse. There is evidence of structural and functional changes in some areas of the brain, which may identify those likely to respond or not to treatments. Despite the geographical differences and lack of consensus regarding approaches, to educate the patients about reducing medication intake, to withdraw overused medications and to start prophylaxis in some sufferers are crucial steps. Emerging treatments as monoclonal antibodies to migraine may result in better adherence and tolerability profiles as well as outcomes.

Sodium Divalproate in Low Alternating Daily Doses for Migraine Prevention: A Retrospective Study.

BACKGROUND AND OBJECTIVE: Sodium divalproate is an effective neuromodulator for migraine prevention. Recommended doses vary from 1,000 to 1,500 mg/day, which may provoke unpleasant side effects as weight gain, tremor, and hair loss. Some patients do respond to lower doses even used once daily in ER presentations, but alternating low daily doses was never studied so far. The aim of this study was to evaluate the adherence, the tolerability, and the efficacy of sodium divalproate (SD) in low alternating daily doses for migraine prevention in patients of a tertiary center. METHODS: Consecutive migraineurs from a tertiary center to whom SD was prescribed as monotherapy from January 2017 until September 2018 were studied retrospectively. The doses were 250 mg alternated with 500 mg and were used based on the treating physician expertise and previous experience with tolerability issues when using higher doses. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months and side effects reported by the patients, were evaluated. RESULTS: Sixty-eight patients (53 women and 15 men, aged 18-58) were included. The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months (adherence rate 73.5%). Weight gain was reported by 15 patients (30%, mean 2.1 kg). At 4 months, HF was reduced to 4.2 days/month (adherence rate 61.8%, n = 42) and weight gain reported by 18 patients (42.8%, mean 2.3 kg). CONCLUSIONS: Despite the retrospective open design, which cannot allow definitive conclusions, SD in low alternating daily doses seems to be effective as with higher doses, but still induce modest weight gain. Controlled studies are necessary to confirm these observations.

Migraine treatment: the doors for the future are open, but with caution and prudence.

Migraine is a burdensome disorder. Current treatments are far from ideal. Recent knowledge has been indicating targets whose antagonism may improve efficacy. It is particularly true with the calcitonin gene-related peptide (CGRP) and the monoclonal antibodies anti-CGRP can interfere with this pathway and decrease the frequency of migraine attacks. Erenumab, fremanezumab and galcanezumab have recently been approved and eptinezumab is likely to be, soon. Although efficacy figures were not spectacular, tolerability and potential higher adherence were noteworthy. However, caution must be exercised. The time frame after the studies was limited to three years and dose administration was restricted to three-monthly doses. The CGRP is present throughout the human body and migraine is a life-long disease, often requiring treatment for decades. It is not known whether this favorable profile can be maintained or will be safe in pregnant women or adolescents. In addition, there were deaths during the studies, which may have happened without a clear relationship. New treatments are welcome, but caution is warranted.

Migraine treatment: the doors for the future are open, but with caution and prudence / Tratamento da migrânea: as portas para o futuro estão abertas, mas com cuidado e parcimônia

ABSTRACT Migraine is a burdensome disorder. Current treatments are far from ideal. Recent knowledge has been indicating targets whose antagonism may improve efficacy. It is particularly true with the calcitonin gene-related peptide (CGRP) and the monoclonal antibodies anti-CGRP can interfere with this pathway and decrease the frequency of migraine attacks. Erenumab, fremanezumab and galcanezumab have recently been approved and eptinezumab is likely to be, soon. Although efficacy figures were not spectacular, tolerability and potential higher adherence were noteworthy. However, caution must be exercised. The time frame after the studies was limited to three years and dose administration was restricted to three-monthly doses. The CGRP is present throughout the human body and migraine is a life-long disease, often requiring treatment for decades. It is not known whether this favorable profile can be maintained or will be safe in pregnant women or adolescents. In addition, there were deaths during the studies, which may have happened without a clear relationship. New treatments are welcome, but caution is warranted.

RESUMO A migrânea é incapacitante. Os tratamentos atuais apresentam resultados abaixo do desejado. O conhecimento atual indica alvos nos quais o bloqueio pode melhorar a eficácia do tratamento. Isso é mais claro com o peptídeo relacionado ao gene da calcitonina (CGRP) e anticorpos monoclonais contra este peptídeo ou seu receptor interferem com a fisiopatologia migranosa e reduzem a frequência da cefaleia. Erenumab, fremanezumab e galcanezumab já foram aprovados. Eptinezumab o será em breve. Embora a eficácia não tenho sido espetacular, a boa tolerabilidade e melhor adesão foram notáveis. No entanto, cautela deve ser empregada. Os estudos se limitaram a observar os pacientes por até três anos e com três doses mensais seguidas. Existe CGRP em todo o organismo e a migrânea é uma doença crônica, não raro requerendo tratamento por décadas. Não se sabe se a tolerabilidade favorável manter-se-á por anos ou em grávidas e adolescentes. Também houve mortes durante os estudos, mesmo sem ligação comprovada. Novos tratamentos são bem-vindos, mas cautela é necessária neste momento.

Medication-overuse headache. Retrospective comparison of preventive treatments.

OBJECTIVE: Medication-overuse headache is commonly seen in tertiary centers. Limited evidence is available regarding treatment. We compared the use of one or two drugs, three drugs, or four pharmacological agents for the prevention of headache. METHODS: This was a retrospective analysis of 149 consecutive patients. Sudden withdrawal and pharmacological prevention with one or more drugs were carried out. Adherence and the decrease of headache frequency of more than 50% were compared after four months between the one or two, three, and four drug groups. RESULTS: There was no difference in adherence (p > 0.6). Headache frequency reduction was shown in 23 (54.8%, one or two drugs), 33 (70%, three drugs) and 11 (55%, four drugs); p = 0.13 and p = 0.98, not significant. There was a tendency towards significance between the one or two drug takers versus the three drug and four drug takers together (p = 0.09). CONCLUSIONS: The use of more drugs was not better at improving headache. However, there is the possibility that acting simultaneously on different sites may promote broader modulation and better outcome.

Medication-overuse headache. Retrospective comparison of preventive treatments / Cefaleia por uso excessivo de medicamentos. Comparação retrospectiva de tratamentos preventivos

ABSTRACT Objectives: Medication-overuse headache is commonly seen in tertiary centers. Limited evidence is available regarding treatment. We compared the use of one or two drugs, three drugs, or four pharmacological agents for the prevention of headache. Methods: This was a retrospective analysis of 149 consecutive patients. Sudden withdrawal and pharmacological prevention with one or more drugs were carried out. Adherence and the decrease of headache frequency of more than 50% were compared after four months between the one or two, three, and four drug groups. Results: There was no difference in adherence (p > 0.6). Headache frequency reduction was shown in 23 (54.8%, one or two drugs), 33 (70%, three drugs) and 11 (55%, four drugs); p = 0.13 and p = 0.98, not significant. There was a tendency towards significance between the one or two drug takers versus the three drug and four drug takers together (p = 0.09). Conclusions: The use of more drugs was not better at improving headache. However, there is the possibility that acting simultaneously on different sites may promote broader modulation and better outcome.

RESUMO Objetivos: Cefaleia por uso excessivo de medicamentos (CEM) é comum em centros terciários. Existe evidência limitada quanto a estratégias de tratamento e se combinar drogas é melhor do que abordagens com monoterapia. Objetivamos comparar o uso de até dois, três ou quatro agentes farmacológicos para a prevenção. Métodos: Estudo retrospectivo de 149 pacientes consecutivos. A suspensão súbita das drogas usadas em excesso e o início de prevenção foram realizados. A adesão e a redução superior a 50% na frequência da cefaleia foram comparadas após quatro meses entre até duas drogas, três drogas e quatro drogas. Resultados: A adesão não foi diferente (p > 0.6). A redução da frequência de cefaleia foi de 23 (54.8%, até duas drogas, 33 (70%, três drogas) e 11 (55%, quatro drogas; p = 0.13 e p = 0.98, não significativo). Houve uma tendência à significância quando comparamos até duas drogas com três e quatro drogas (p = 0.09). Conclusões: Não demonstramos superioridade de mais drogas, comparando-se a um ou dois medicamentos. Acreditamos na possibilidade de atuação em sítios de diferentes de forma simultânea e a modulação mais abrangente com melhores parâmetros evolutivos.

Amitriptyline and intraoral devices for migraine prevention: a randomized comparative trial.

OBJECTIVES: Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at evaluating the effectiveness of the NTI-tss and to compare its efficacy with amitriptyline and with a sham intraoral device in the preventive treatment of migraine. METHODS: Consecutive patients with migraine were randomized to receive 25 mg of amitriptyline/day (n = 34), NTI-tss (n = 33) and a non-occlusal splint (n = 30). The headache frequency was evaluated at six and 12 weeks. RESULTS: The amitriptyline group showed, respectively, 60% and 64% reduction in attack frequency at six and 12 weeks (P = 0.000). In the NTI-tss and non-occlusal splint groups, reduction was 39% and 30%, respectively, at six weeks and 48% for both groups at 12 weeks. CONCLUSIONS: Amitriptyline proved superior to the NTI-tss and the non-occlusal splint. Despite its approval by the United States Food and Drug Administration, the NTI-tss was not superior to a sham device.

Amitriptyline and intraoral devices for migraine prevention: a randomized comparative trial / Amitriptilina e dispositivos intraorais para a prevenção da migrânea: estudo randomizado e comparativo

ABSTRACT Objectives: Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at evaluating the effectiveness of the NTI-tss and to compare its efficacy with amitriptyline and with a sham intraoral device in the preventive treatment of migraine. Methods: Consecutive patients with migraine were randomized to receive 25 mg of amitriptyline/day (n = 34), NTI-tss (n = 33) and a non-occlusal splint (n = 30). The headache frequency was evaluated at six and 12 weeks. Results: The amitriptyline group showed, respectively, 60% and 64% reduction in attack frequency at six and 12 weeks (P = 0.000). In the NTI-tss and non-occlusal splint groups, reduction was 39% and 30%, respectively, at six weeks and 48% for both groups at 12 weeks. Conclusions: Amitriptyline proved superior to the NTI-tss and the non-occlusal splint. Despite its approval by the United States Food and Drug Administration, the NTI-tss was not superior to a sham device.

RESUMO Objetivo: Tratamentos não farmacológicos como o Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), são aprovados para a prevenção da migrânea. Avaliamos a eficácia do NTI-tss no tratamento preventivo da migrânea e comparamos sua eficácia com a de um medicamento tradicional (amitriptilina) e com um dispositivo intraoral que não interfere com a oclusão (placa palatina). Métodos: Pacientes consecutivos com migrânea foram randomizados e receberam 25mg de amitriptilina/dia (n = 34), NTI-tss (n = 33) ou placa palatina não oclusal (n = 30). A frequência da cefaleia foi comparada após seis e 12 semanas. Resultados: No grupo da amitriptilina houve redução de 60% em seis semanas e de 64% em 12 semanas (P = 0.000). Nos grupos do NTI-tss e da placa não oclusal a redução foi respectivamente de 39% e 30% após seis semanas, e de 48% para ambos em 12 semanas. Conclusões: Amitriptilina foi superior ao NTI-tss e à placa palatina no tratamento da migrânea sem aura. O NTI-tss obteve resultados similares aos da placa não oclusal.

Correction: Krymchantowski, A.V.; et al. Medication-Overuse Headache: Differences between Daily and Near-Daily Headache Patients; Brain Sciences 2016, 6, 30.

n/a.

Medication-Overuse Headache: Protocols and Outcomes in 149 Consecutive Patients in a Tertiary Brazilian Headache Center.

AIM: Medication-overuse headache (MOH) is a challenging clinical disorder often resulting in frustration for patients and physicians. Adherence issues are common and limited treatment evidence is an obstacle to effective care. Individual bias usually directs the treatment. The aim of this study was to evaluate outcome and treatment strategies in consecutive MOH patients from a tertiary center. METHODS: Every consecutive patient seen between January and December 2014 with the diagnosis of MOH was included. Psychiatric comorbidities, inability to report baseline headache frequency, current or previous 2-month use of preventive medications, and refusal to sign informed consent were exclusion criteria. The patients were evaluated by the same specialist (AVK) in thorough initial consultations. The diagnosis and treatment strategies were clearly explained, and a detailed headache diary was given to all patients. Endpoints were headache frequency and adherence after 2, 4, and 8 months. RESULTS: One hundred sixty-eight patients (31 M, 137 F) met the inclusion criteria. Nineteen patients (11.3%) were excluded. All patients had migraine or chronic migraine as primary headache. Mean baseline frequency was 24.8 headache days/month, average headache history was 20.6 years (1-37), and mean time with > 15 headache days/month was 4.8 years (.5-32). All patients were overusing acute symptomatic medications (SM), and 59 (39.5%) were using more than one pharmacological class. Outpatient withdrawal from overused medications was carried out with all patients, who received different preventive treatment choices and triptan plus NSAID for the acute attacks (maximum of 2 days/week). One hundred and one patients (67.8%) received prednisone during the first 5-7 days. After 2 months, 30 (20.1%) were lost to follow-up, and in those who followed up, the mean headache frequency decreased to 10.7 headache days/month (ITT 13.1). After 4 and 8 months, 109 and 105 patients, respectively, were under treatment, with a mean headache frequency of 7.9 and 8.2 headache days/month. Patients who received prednisone did not perform better than those who did not (P = .3032, 5 d vs no prednisone; P = .639, 7 d vs no prednisone). CONCLUSIONS: Withdrawing overused medications, starting prevention, and motivating patients may have helped the high adherence rates and decreasing headache frequency. Additionally, real-world patient studies are scarce and may be useful to guide clinicians struggling to help their daily headache patients. Open studies do not allow definitive conclusions and controlled studies with this subset of patients are necessary.

Medication-Overuse Headache: Differences between Daily and Near-Daily Headache Patients.

UNLABELLED: Medication-overuse headache (MOH) is a challenging neurological disease, which brings frustration for sufferers and treating physicians. The patient's lack of adherence and limited treatment evidence are frequent. The aim of this study was to compare the outcome and treatment strategies between consecutive MOH patients with daily and near-daily headache from a tertiary center. METHODS: Every consecutive patient seen between January and December 2014 with the diagnosis of MOH was included. Psychiatric comorbidities, inability to inform baseline headache frequency, current or previous two-month use of preventive medications, and refusal to sign informed consent were exclusion criteria. The patients were evaluated in thorough initial consultations and divided in two groups based on their baseline headache frequency. The diagnosis and treatment strategies were clearly explained. The filling out of a detailed headache diary was requested from all patients. Endpoints compared headache frequency and adherence after two, four, and eight months between the two study groups. RESULTS: One-hundred sixty-eight patients (31 male, 137 female) met the inclusion criteria. Nineteen patients (11.3%) were excluded. All patients had migraine or chronic migraine as primary headaches. Eighty had daily (DH), and 69 near-daily headache (NDH), at baseline consultation. Mean baseline frequency was 24.8 headache days/month (18.9 days/month for the near-daily group), average headache history was 20.6 years and mean time with >15 headache days/month was 4.8 years. Outpatient withdrawal, starting prevention, and enforcing the correct use of rescue therapy was carried out with all patients. After two months, 88% of the DH and 71% of the NDH groups adhered to treatment (p = 0.0002). The HF decreased to 12 and 9 headache days/month, respectively in DH and NDH groups (p > 0.05, non-significant) (Intention-to-treat (ITT) 14 DH; 12 NDH; p > 0.05). After four and eight months, 86.3% and 83.7% of the DH patients, and 59.4% and 55% of the NDH patients were still under treatment (p = 0.0003 and p = 0.0001). The HF decreased, respectively, to nine and nine headache days/month in the DH patients compared to 6 and 7 headache days/month in the NDH group (p > 0.05) (ITT, 12; 12; DH; 10; 11; NDH; p > 0.05). CONCLUSIONS: Although open studies provide limited conclusions, withdrawing overused medications and starting prevention may have helped the favorable outcomes. However, daily headache patients had a significantly higher adherence and lower relapse rates than near-daily headache patients, despite a considerable reduced headache frequency in both groups. Additionally, real-world patient studies are scarce and the comparison between these two subsets of patients may be useful to guide clinicians in approaching their patients. Controlled studies are necessary to confirm these observations.

TEV-48125 for the preventive treatment of chronic migraine: Efficacy at early time points.

OBJECTIVE: To evaluate the onset of efficacy of TEV-48125, a monoclonal antibody against calcitonin gene-related peptide, recently shown to be effective for the preventive treatment of chronic migraine (CM) and high-frequency episodic migraine. METHODS: A randomized placebo-controlled study tested once-monthly injections of TEV-48125 675/225 mg or 900 mg vs placebo. Headache information was captured daily using an electronic headache diary. The primary endpoint was change from baseline in the number of headache hours in month 3. Herein, we assess the efficacy of each dose at earlier time points. RESULTS: The sample consisted of 261 patients. For headache hours, the 675/225-mg dose separated from placebo on day 7 and the 900-mg dose separated from placebo after 3 days of therapy (p = 0.048 and p = 0.033, respectively). For both the 675/225-mg and 900-mg doses, the improvement was sustained through the second (p = 0.004 and p < 0.001) and third (p = 0.025 and p < 0.001) weeks of therapy and throughout the study (month 3, p = 0.0386 and p = 0.0057). For change in weekly headache days of at least moderate intensity, both doses were superior to placebo at week 2 (p = 0.031 and p = 0.005). CONCLUSIONS: TEV-48125 demonstrated a significant improvement within 1 week of therapy initiation in patients with CM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, TEV-48125 significantly decreases the number of headache hours within 3 to 7 days of injection.

Prevalence and burden of headaches as assessed by the health family program.

BACKGROUND: Unified health systems often have Family Health Programs (FHPs) as a core component of their preventive and early curative strategies. In Brazil, the FHP is established to proactively identify diseases such as diabetes and hypertension. OBJECTIVE: To use the FHP in order to assess the prevalence of primary headaches, as per the Second Edition of the International Classification of Headache Disorders in a Brazilian city covered by the program, and to document the burden of migraine and tension-type headache (TTH) in this population. METHODS: FHP agents were trained on how to apply questionnaires that screened for the occurrence of headaches in the past year. Screening method had been previously validated. Respondents that screened positively were interviewed by a headache specialist, and all their headache types were classified. Additionally, disability (Migraine Disability Assessment Scale and Headache Impact Test) and health-related quality of life were assessed. RESULTS: The 1-year prevalence of migraine was 18.2% [95% confidence interval = 13.7; 23.5]. TTH occurred in 22.9% [18.0%; 28.6%]. Other primary headaches occurred in 10.8% of the participants. Idiopathic stabbing headache was significantly more common in individuals with migraine relative to those without migraine (44.7% vs 10.3%, P < .001). Contrasting with TTH, migraineurs had a mean of 3.1 headache types vs 1.9 in TTH (P < .001). Secondary headaches occurred in 21.7% of the participants over a 1-year period [16.9%; 27.3%]. Most cases were headaches attributed to infection (mostly respiratory). The impact of migraine was bimodal. Most sufferers had little impact, but a sizable minority was severely impaired. CONCLUSIONS: The FHP can be effectively used to bring individuals with headache to the attention of providers. Future investigations should assess whether this increased attention translates into improved outcomes.

Topiramate vs divalproex sodium in the preventive treatment of migraine: a prospective "real-world" study.

BACKGROUND AND OBJECTIVES: Certain neuromodulators, most notably topiramate (TPM) and divalproex sodium (DVP), are effective preventive agents for migraine. Published data from head-to-head studies comparing TPM and DVP are not available. The purpose of this study was to compare TPM and DVP for the prophyaxis of migraine in a "real-world" setting. METHODS: At 2 centers and over a period of 12 months we prospectively evaluated and treated a consecutive series of migraine patients. At baseline all were experiencing less than 15 headache days/month, and we treated all patients requiring prophylactic therapy with either TPM or DVP. We evaluated adherence, headache frequency (HF) and tolerability after 3 months of treatment. TPM treatment was initiated at 25 mg daily and increased every 10 days (25 mg) to a target of 150 mg/day (2 divided doses/day). Treatment with DVP was initiated at 250 mg daily and sequentially titrated up to 500 mg twice daily. All patients were naïve to the use of TPM and DVP. RESULTS: One hundred and twenty patients (104 women and 16 men of ages 18 to 68, mean 41.2 years) were included. Topiramate selectively was prescribed to 69 patients and DVP selectively to 51. Baseline HF for both groups was similar (8 ± 4 headache days/month). By intention to treat analysis at 3 months, 40 (58%) of patients initially treated with TPM and 26 (51%) of those initially treated with DVP experienced a reduction in HF of >50% (P = NS). Ten patients (14.5%) initially treated with TPM and 8 (15.7%) initially treated with DVP did not return for follow up or were begun on alternative prophylactic therapy. The most common side effects manifested by TPM patients were weight loss (50% of those who completed the treatment period), paresthesia (48%), and cognitive disturbances (20%), whereas DVP patients who completed the treatment period reported weight gain, hair loss, and gastrointestinal symptoms (approximately 24% for each). The mean doses achieved by those completing the study were 140 mg/day for TPM and 890 mg/day for DVP. CONCLUSIONS: Although any conclusions from this investigation necessarily are limited because of our study's open-label nonrandomized design, these results suggest that TPM and DVP are reasonably effective and generally well tolerated when used to treat a "real-world" population of episodic migraineurs who require prophylaxis.

A double-blind, randomized clinical trial assessing the effects of a single dose of preemptive anti-inflammatory treatment in orthodontic pain.

OBJECTIVE: Strategies about how to mitigate or prevent the appearance of pain associated with orthodontic treatment are poorly defined. Herein we conduct a prospective, double-blind, randomized controlled clinical trial assessing the effects of a single dose of anti-inflammatory medication to preemptively treat pain following the placement of orthodontic separating elastics. MATERIALS AND METHODS: Fifty one participants were randomly selected and divided into three groups: (a) 17 patients took placebo one hour prior to the elastic separator placement; (b) 17 patients took 400 mg lumiracoxib one hour prior to the elastic separator placement; and (c) 17 patients didn't take anything prior to the procedure. Discomfort and pain intensity levels were measured by an analog 10-points visual scale at 2 hours, 6 hours, 24 hours, 2 days and 4 days after the procedure. RESULTS: When comparing the three groups (no treatment, placebo and active) no significant differences were found. Nonetheless, pain severity was always lower in individuals receiving the drug. Similar pattern was seen for the other time points. CONCLUSIONS: Our study does not support the use of a single dose of medication with anti-inflammatory properties in the preemptive treatment of pain following an orthodontic procedure. Further investigation is required in order to ascertain whether recurrent doses (vs a single dose) can impact outcomes.