Migraine ICYMI

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y

Key clinical point: The clinical characteristics of menstrual migraine (MM) quantitatively differ from those of non-MM, with its symptoms being more severe and inadequately captured by the current diagnostic criteria, necessitating formulation of new criteria for MM diagnosis.

Major finding: The prevalence rates of MM and non-MM were 16.6% and 45.9%, respectively. The MM vs non-MM group was more likely to have more frequent (odds ratio [OR] 7.21), longer duration (OR 2.32), and more severe (OR 1.17) migraine attacks; less frequent nonmigraine headaches (OR 0.31); better treatment outcomes with triptans (OR 1.66); better improvement in migraine attacks during late pregnancy (OR 5.10); and a faster reappearance of migraine attacks postpartum (OR 3.19; all P < .001).

Study details: This case-control study included 12,618 patients with migraine (3434 men and 9184 women).

Disclosures: This study was funded by the Candys Foundation and others. S Brunak and OB Pedersen declared receiving grants, research funds, personal fees, or compensation as a managing board member from or holding stocks in various organizations. The other authors disclosed no conflicts of interest.

Source: Chalmer MA et al. Population-based characterization of menstrual migraine and proposed diagnostic criteria. JAMA Netw Open. 2023;6:e2313235 (May 15). doi: 10.1001/jamanetworkopen.2023.13235

Key clinical point: The clinical characteristics of menstrual migraine (MM) quantitatively differ from those of non-MM, with its symptoms being more severe and inadequately captured by the current diagnostic criteria, necessitating formulation of new criteria for MM diagnosis.

Major finding: The prevalence rates of MM and non-MM were 16.6% and 45.9%, respectively. The MM vs non-MM group was more likely to have more frequent (odds ratio [OR] 7.21), longer duration (OR 2.32), and more severe (OR 1.17) migraine attacks; less frequent nonmigraine headaches (OR 0.31); better treatment outcomes with triptans (OR 1.66); better improvement in migraine attacks during late pregnancy (OR 5.10); and a faster reappearance of migraine attacks postpartum (OR 3.19; all P < .001).

Study details: This case-control study included 12,618 patients with migraine (3434 men and 9184 women).

Disclosures: This study was funded by the Candys Foundation and others. S Brunak and OB Pedersen declared receiving grants, research funds, personal fees, or compensation as a managing board member from or holding stocks in various organizations. The other authors disclosed no conflicts of interest.

Source: Chalmer MA et al. Population-based characterization of menstrual migraine and proposed diagnostic criteria. JAMA Netw Open. 2023;6:e2313235 (May 15). doi: 10.1001/jamanetworkopen.2023.13235

Key clinical point: The clinical characteristics of menstrual migraine (MM) quantitatively differ from those of non-MM, with its symptoms being more severe and inadequately captured by the current diagnostic criteria, necessitating formulation of new criteria for MM diagnosis.

Major finding: The prevalence rates of MM and non-MM were 16.6% and 45.9%, respectively. The MM vs non-MM group was more likely to have more frequent (odds ratio [OR] 7.21), longer duration (OR 2.32), and more severe (OR 1.17) migraine attacks; less frequent nonmigraine headaches (OR 0.31); better treatment outcomes with triptans (OR 1.66); better improvement in migraine attacks during late pregnancy (OR 5.10); and a faster reappearance of migraine attacks postpartum (OR 3.19; all P < .001).

Study details: This case-control study included 12,618 patients with migraine (3434 men and 9184 women).

Disclosures: This study was funded by the Candys Foundation and others. S Brunak and OB Pedersen declared receiving grants, research funds, personal fees, or compensation as a managing board member from or holding stocks in various organizations. The other authors disclosed no conflicts of interest.

Source: Chalmer MA et al. Population-based characterization of menstrual migraine and proposed diagnostic criteria. JAMA Netw Open. 2023;6:e2313235 (May 15). doi: 10.1001/jamanetworkopen.2023.13235

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600