Migraine ICYMI

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781

Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

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

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

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

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

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

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

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

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

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

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

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

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

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

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

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

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

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

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

For adolescents with migraine or other recurring types of headaches, planning and structuring a transition from pediatric to adult health services is recommended for a potential of better outcomes, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.

“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.

Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”

Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.

“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
 

TRAQ questionnaire is helpful

The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.

“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.

Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.

Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.

“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.

With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.

Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.

In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.

“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.

The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
 

Poor transition linked to poor outcomes

A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.

“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.

This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.

“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.

Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.

For adolescents with migraine or other recurring types of headaches, planning and structuring a transition from pediatric to adult health services is recommended for a potential of better outcomes, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.

“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.

Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”

Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.

“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
 

TRAQ questionnaire is helpful

The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.

“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.

Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.

Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.

“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.

With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.

Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.

In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.

“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.

The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
 

Poor transition linked to poor outcomes

A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.

“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.

This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.

“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.

Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.

For adolescents with migraine or other recurring types of headaches, planning and structuring a transition from pediatric to adult health services is recommended for a potential of better outcomes, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.

“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.

Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”

Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.

“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
 

TRAQ questionnaire is helpful

The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.

“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.

Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.

Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.

“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.

With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.

Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.

In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.

“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.

The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
 

Poor transition linked to poor outcomes

A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.

“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.

This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.

“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.

Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.

Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
 
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
 
How do you switch a patient from a triptan to a gepant? 
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the

triptan is not working well for them or they have significant adverse events, I will move
on.
 
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin. 
 
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
 
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
 
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of

patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
 
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.

Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),

which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
 
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
 
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
 
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.

Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor. 

The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
 
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.

Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
 
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
 
How do you switch a patient from a triptan to a gepant? 
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the

triptan is not working well for them or they have significant adverse events, I will move
on.
 
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin. 
 
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
 
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
 
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of

patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
 
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.

Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),

which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
 
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
 
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
 
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.

Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor. 

The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
 
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.

Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
 
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
 
How do you switch a patient from a triptan to a gepant? 
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the

triptan is not working well for them or they have significant adverse events, I will move
on.
 
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin. 
 
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
 
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
 
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of

patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
 
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.

Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),

which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
 
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
 
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
 
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.

Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor. 

The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
 
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.