Utility of Topiramate for the Treatment of Patients with Chronic Migraine in the Presence or Absence of Acute Medication Overuse

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo- controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

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The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study

The Journal of Headache and Pain ◽

10.1186/s10194-020-01173-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Stephen D. Silberstein ◽

Joshua M. Cohen ◽

Michael J. Seminerio ◽

Ronghua Yang ◽

Sait Ashina ◽

...

Keyword(s):

Chronic Migraine ◽

Medication Overuse ◽

Humanized Monoclonal Antibody ◽

Acute Medication ◽

Calcitonin Gene ◽

Acute Headache ◽

Post Hoc ◽

The Impact ◽

Adjusted Least Squares

Abstract Background We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO). Methods In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores. Results Of 1130 patients enrolled, 587 (51.9%) had baseline MO. Fremanezumab reduced placebo-adjusted least-squares mean (95% confidence interval) monthly HDs (− 2.2 [− 3.1 to − 1.2] and − 2.7 [− 3.7 to − 1.8]; P < 0.0001) in patients with MO and without MO (quarterly − 1.4 [− 2.3 to − 0.5], P = 0.0026; monthly − 1.4 [− 2.3 to − 0.6], P = 0.0017). Significantly more fremanezumab-treated patients had ≥ 50% reduction in HDs versus placebo, regardless of baseline MO (with: quarterly 70/201 [34.8%], monthly 78/198 [39.4%] vs placebo 26/188 [13.8%]; without: quarterly 71/174 [40.8%], monthly 75/177 [42.4%] vs placebo 41/183 [22.4%]). Fremanezumab improved HIT-6 and MSQoL scores. Significantly more fremanezumab-treated patients reverted to no MO (quarterly 111/201 [55.2%], monthly 120/198 [60.6%]) versus placebo (87/188 [46.3%]). Conclusions Fremanezumab is effective for prevention of migraine in patients with CM, regardless of MO, and demonstrated a benefit over placebo in reducing MO. Trial registration ClinicalTrials.gov NCT02621931 (HALO CM), registered December 12, 2012.

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Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

The Journal of Headache and Pain ◽

10.1186/s10194-021-01279-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Messoud Ashina ◽

Joshua M. Cohen ◽

Maja Galic ◽

Verena Ramirez Campos ◽

Steve Barash ◽

...

Keyword(s):

Chronic Migraine ◽

Medication Use ◽

Episodic Migraine ◽

Inadequate Response ◽

Open Label ◽

Double Blind ◽

Moderate Severity ◽

Preventive Medication ◽

Open Label Extension ◽

Acute Headache

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%). Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).

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Treatment of medication-overuse headache: A systematic review

Cephalalgia ◽

10.1177/0333102415593088 ◽

2015 ◽

Vol 36 (4) ◽

pp. 371-386 ◽

Cited By ~ 72

Author(s):

Chia-Chun Chiang ◽

Todd J Schwedt ◽

Shuu-Jiun Wang ◽

David W Dodick

Keyword(s):

Medication Overuse ◽

Medication Overuse Headache ◽

Treatment Strategies ◽

Preventive Treatment ◽

Early Discontinuation ◽

Level Of Evidence ◽

Preventive Medication ◽

Long Term Prognosis ◽

Acute Headache

Introduction The objective of this review is to provide an evidence-based discussion of different treatment strategies for medication-overuse headache (MOH). Method We searched PubMed for articles discussing the treatment and prognosis of MOH published between 2004 and August 2014. Titles, abstract and articles were reviewed systematically. The level of evidence provided by each study of the included articles was determined according to the American Academy of Neurology Clinical practice guideline manual. We discuss the level of evidence to support the early discontinuation/withdrawal of overused medications, the level of evidence to support the use of preventive treatment, the short- and long-term prognosis, and the outcome according to the class of drug overused in patients diagnosed with MOH. Results The initial search resulted in 1313 articles; 68 articles met our inclusion criteria and were discussed. The level of evidence to support early discontinuation of overused medications alone is low due to the absence of controlled studies. Adding preventive medication to early discontinuation led to a better outcome than early discontinuation alone. For patients with chronic migraine (CM) and medication overuse (MO), there are large randomized control trials supporting the use of onabotulinumtoxinA and topiramate without early discontinuation of overuse; however, the evidence is limited since data were obtained from post hoc analysis. Conclusion Considering current available evidence and the systemic toxicity of overusing acute headache medication, we suggest discontinuation of the overused medication with the addition of preventive medication. Appropriately sized, randomized controlled trials evaluating the safety and long-term efficacy of preventive medication plus early discontinuation of overuse vs preventive medication alone vs early discontinuation of overuse alone are needed.

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P.033 Eptinezumab reduced acute medication use in patients with chronic migraine and medication-overuse headache: subgroup analysis of Promise-2

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.315 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S29-S29

Author(s):

MJ Marmura ◽

H Diener ◽

J Hirman ◽

R Cady ◽

T Brevig ◽

...

Keyword(s):

Chronic Migraine ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Baseline Period ◽

Migraine Treatment ◽

Medication History ◽

Medication Class ◽

The Us ◽

Acute Headache ◽

The Impact

Background: Eptinezumab is a preventive migraine treatment approved in the US. We evaluated the impact of eptinezumab on acute headache medication (AHM) use in patients diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) in PROMISE-2. Methods: PROMISE-2 randomized patients with CM to eptinezumab 100mg, 300mg, or placebo for 2 intravenous doses administered every 12 weeks. Trained investigators diagnosed MOH at screening using 3-month medication history and ICHD-3b criteria. Endpoints included days/month of any AHM use (days of ≥1 medication class), total AHM use (summed days for each medication class), and triptan use over Weeks 1-12 and 13-24. AHM classes included triptan, ergot, opioid, simple analgesic, and combination analgesic. Results: Of 1072 PROMISE-2 patients, 431 (40.2%) were diagnosed with MOH (100mg, n=139; 300mg, n=147; placebo, n=145). During the 28-day baseline period, mean days of any AHM was ~16.4, total AHM was ~20.4, and triptan was ~8.9 across treatment arms. Over Weeks 1-12, mean days/month of any AHM was 8.8 (100mg), 9.9 (300mg), and 11.8 (placebo); total AHM was 10.8, 12.2, and 14.8; triptan was 4.3, 4.4, and 6.4. Similar or lower rates were observed over Weeks 13-24. Conclusions: In patients diagnosed with both CM and MOH, eptinezumab treatment reduced AHM use.

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Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

The Journal of Headache and Pain ◽

10.1186/s10194-021-01328-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Edoardo Caronna ◽

Victor José Gallardo ◽

Alicia Alpuente ◽

Marta Torres-Ferrus ◽

Patricia Pozo-Rosich

Keyword(s):

Monoclonal Antibodies ◽

Chronic Migraine ◽

Medication Overuse ◽

Real Life ◽

Daily Practice ◽

Headache Frequency ◽

Electronic Diary ◽

Life Effectiveness ◽

Medication Intake ◽

Acute Medication

Abstract Background In daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort. Methods This is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment. Results Of 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049). Conclusions In real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.

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Medication Overuse and Headache Burden: Results From the CaMEO Study

Neurology Clinical Practice ◽

10.1212/cpj.0000000000001037 ◽

2021 ◽

pp. 10.1212/CPJ.0000000000001037

Author(s):

Todd J. Schwedt ◽

Dawn C. Buse ◽

Charles E. Argoff ◽

Michael L. Reed ◽

Kristina M. Fanning ◽

...

Keyword(s):

Logistic Regression ◽

Chronic Migraine ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Urgent Care ◽

Systematic Sampling ◽

Factors Associated ◽

Link Type ◽

Increased Risk ◽

Preventive Medication

AbstractObjective:To estimate the relative frequency of acute medication overuse (AMO) among people with episodic migraine (EM) and chronic migraine (CM), to characterize the types of acute medications overused for migraine, and to identify factors associated with AMO.Methods:We analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study (ClinicalTrials.gov, NCT01648530), a cross-sectional and longitudinal Internet study that included a systematic sampling of the US population. From September 2012 to November 2013, the CaMEO Study respondents participated in different modules to collect data on the clinical course of migraine, family burden, barriers to care, endophenotypes, and comorbidities. Among people who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition (ICHD-3), we evaluated types and frequency of medications used for headache/migraine, selected comorbidities, and emergency department (ED) and urgent care (UC) use. AMO was defined by days/month of medication use as specified by ICHD-3 criteria for medication overuse headache (MOH) without the requirement for ≥15 monthly headache days (MHDs). Nested, multivariable binary logistic regression modeling was used to identify factors associated with increased risk of AMO.Results:Of 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met AMO criteria. Approximately 67.9% (2,021/2,975) of AMO respondents reported <15 MHDs. Simple analgesics, combination analgesics, and opioids were the medication classes most commonly overused. Factors associated with AMO in the final multivariable logistic regression model included ≥15 MHDs, moderate to severe disability, severe migraine interictal burden, use of preventive medication, and an ED/UC visit for headache within 6 months.Conclusions:Approximately two-thirds of respondents with AMO reported <15 MHDs and therefore did not meet criteria for MOH. Those with AMO had greater disease burden and increased ED/UC utilization relative to people with migraine but not AMO.

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Acupuncture versus topiramate in chronic migraine prophylaxis: A randomized clinical trial

Cephalalgia ◽

10.1177/0333102411420585 ◽

2011 ◽

Vol 31 (15) ◽

pp. 1510-1521 ◽

Cited By ~ 60

Author(s):

C-P Yang ◽

M-H Chang ◽

P-E Liu ◽

T-C Li ◽

C-L Hsieh ◽

...

Keyword(s):

Chronic Migraine ◽

Prophylactic Treatment ◽

Medication Overuse ◽

Severe Headache ◽

Migraine Prophylaxis ◽

Acupuncture Group ◽

Maintenance Period ◽

Acute Medication ◽

Group A ◽

The Mean

Background: The aim of this study was to investigate the efficacy and tolerability of acupuncture compared with topiramate treatment in chronic migraine (CM) prophylaxis. Methods: A total of 66 consecutive and prospective CM patients were randomly divided into two treatment arms: 1) acupuncture group: acupuncture administered in 24 sessions over 12 weeks (n = 33); and 2) topiramate group: a 4-week titration, initiated at 25 mg/day and increased by 25 mg/day weekly to a maximum of 100 mg/day followed by an 8-week maintenance period (n = 33). Results: A significantly larger decrease in the mean monthly number of moderate/severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days was observed in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (p < .01) Significant differences favoring acupuncture were also observed for all secondary efficacy variables. These significant differences still existed when we focused on those patients who were overusing acute medication. Adverse events occurred in 6% of acupuncture group and 66% of topiramate group. Conclusion: We suggest that acupuncture could be considered a treatment option for CM patients willing to undergo this prophylactic treatment, even for those patients with medication overuse.

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Sleep Disturbances among Persons who are Visually Impaired: Survey of Dog Guide Users

Journal of Visual Impairment & Blindness ◽

10.1177/0145482x9809200712 ◽

1998 ◽

Vol 92 (7) ◽

pp. 522-530 ◽

Cited By ~ 2

Author(s):

Massoud K. Fouladi ◽

Merrick J. Moseley ◽

Helen S. Jones ◽

Micheal J. Tobin

Keyword(s):

Visual Acuity ◽

Risk Factor ◽

Visually Impaired ◽

Sleep Disturbances ◽

Significant Risk ◽

Significant Risk Factor ◽

Quality Of Sleep ◽

Disturbed Sleep ◽

Photic Input

It is claimed that blindness may predispose individuals to disturbed sleep because light is an important mechanism for entraining circadian rhythms. One in five respondents in a survey described the quality of their sleep as either poor or very poor. Exercise was associated with better sleep, and depression with poorer sleep. That visual acuity did not predict the quality of sleep casts doubt on the notion that restricted visual (photic) input is a widespread cause of sleep disturbance among persons who are visually impaired. As with sighted persons, depression appears to be a highly significant risk factor for disturbed sleep in persons who are visually impaired.

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Chronic Migraine and Medication-Overuse Headache Through the Ages

Cephalalgia ◽

10.1111/j.1468-2982.2005.00868.x ◽

2005 ◽

Vol 25 (5) ◽

pp. 378-390 ◽

Cited By ~ 26

Author(s):

CJ Boes ◽

DJ Capobianco

Keyword(s):

Chronic Migraine ◽

English Language ◽

Medication Overuse ◽

International Headache Society ◽

Medication Overuse Headache ◽

Headache Frequency ◽

Ihs Criteria ◽

Acute Headache

We set out to review early descriptions of chronic migraine and medication-overuse headache. The International Headache Society (IHS) recently gave criteria for chronic migraine and medication-overuse headache. Chronic migraine was absent from the 1988 IHS criteria. Peters and Horton described ergotamine-overuse headache in 1951. In the 1980s it was more fully appreciated that overuse of other acute headache medications could increase headache frequency. We reviewed published English-language papers and book chapters. Willis (1672), Oppenheim (1900), Collier (1922), Balyeat (1933), and von Storch (1937) all described chronic migraine. Lennox (1934), O'Sullivan (1936), Silfverskiöld (1947), Graham (1955), Friedman (1955), and Lippman (1955) wrote about ergotamine-overuse headache. Graham (1955), Friedman (1955), Lippman (1955), and Horton and Peters (1963) outlined withdrawal protocols. Chronic migraine has been mentioned in the literature for centuries, while medication-overuse headache has been written about for decades. Graham, Friedman, and Lippman deserve credit for separately reporting the first ergotamine withdrawal programmes.

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