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Effect of CGRP mAb rollout on prescription patterns of other migraine preventive therapies
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
BMI and migraine risk in adolescents: What’s the link?
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
Anti-CGRP antibodies improve depressive symptoms in migraine
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
Real-world evidence on efficacy of anti-CGRP mAbs in elderly patients with migraine
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
Ketogenic diets improve symptoms and fatigue in chronic and high-frequency episodic migraine
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
Headache after drinking red wine? This could be why
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Robert Louis Stevenson famously said, “Wine is bottled poetry.” And I think it works quite well. I’ve had wines that are simple, elegant, and unpretentious like Emily Dickinson, and passionate and mysterious like Pablo Neruda. And I’ve had wines that are more analogous to the limerick you might read scrawled on a rest-stop bathroom wall. Those ones give me headaches.
Headaches are common, and headaches after drinking alcohol are particularly common. An interesting epidemiologic phenomenon, not yet adequately explained, is why red wine is associated with more headache than other forms of alcohol. There have been many studies fingering many suspects, from sulfites to tannins to various phenolic compounds, but none have really provided a concrete explanation for what might be going on.
A new hypothesis came to the fore on Nov. 20 in the journal Scientific Reports:
To understand the idea, first a reminder of what happens when you drink alcohol, physiologically.
Alcohol is metabolized by the enzyme alcohol dehydrogenase in the gut and then in the liver. That turns it into acetaldehyde, a toxic metabolite. In most of us, aldehyde dehydrogenase (ALDH) quickly metabolizes acetaldehyde to the inert acetate, which can be safely excreted.
I say “most of us” because some populations, particularly those with East Asian ancestry, have a mutation in the ALDH gene which can lead to accumulation of toxic acetaldehyde with alcohol consumption – leading to facial flushing, nausea, and headache.
We can also inhibit the enzyme medically. That’s what the drug disulfiram, also known as Antabuse, does. It doesn’t prevent you from wanting to drink; it makes the consequences of drinking incredibly aversive.
The researchers focused in on the aldehyde dehydrogenase enzyme and conducted a screening study. Are there any compounds in red wine that naturally inhibit ALDH?
The results pointed squarely at quercetin, and particularly its metabolite quercetin glucuronide, which, at 20 micromolar concentrations, inhibited about 80% of ALDH activity.
Quercetin is a flavonoid – a compound that gives color to a variety of vegetables and fruits, including grapes. In a test tube, it is an antioxidant, which is enough evidence to spawn a small quercetin-as-supplement industry, but there is no convincing evidence that it is medically useful. The authors then examined the concentration of quercetin glucuronide to achieve various inhibitions of ALDH, as you can see in this graph here.
By about 10 micromolar, we see a decent amount of inhibition. Disulfiram is about 10 times more potent than that, but then again, you don’t drink three glasses of disulfiram with Thanksgiving dinner.
This is where this study stops. But it obviously tells us very little about what might be happening in the human body. For that, we need to ask the question: Can we get our quercetin levels to 10 micromolar? Is that remotely achievable?
Let’s start with how much quercetin there is in red wine. Like all things wine, it varies, but this study examining Australian wines found mean concentrations of 11 mg/L. The highest value I saw was close to 50 mg/L.
So let’s do some math. To make the numbers easy, let’s say you drank a liter of Australian wine, taking in 50 mg of quercetin glucuronide.
How much of that gets into your bloodstream? Some studies suggest a bioavailability of less than 1%, which basically means none and should probably put the quercetin hypothesis to bed. But there is some variation here too; it seems to depend on the form of quercetin you ingest.
Let’s say all 50 mg gets into your bloodstream. What blood concentration would that lead to? Well, I’ll keep the stoichiometry in the graphics and just say that if we assume that the volume of distribution of the compound is restricted to plasma alone, then you could achieve similar concentrations to what was done in petri dishes during this study.
Of course, if quercetin is really the culprit behind red wine headache, I have some questions: Why aren’t the Amazon reviews of quercetin supplements chock full of warnings not to take them with alcohol? And other foods have way higher quercetin concentration than wine, but you don’t hear people warning not to take your red onions with alcohol, or your capers, or lingonberries.
There’s some more work to be done here – most importantly, some human studies. Let’s give people wine with different amounts of quercetin and see what happens. Sign me up. Seriously.
As for Thanksgiving, it’s worth noting that cranberries have a lot of quercetin in them. So between the cranberry sauce, the Beaujolais, and your uncle ranting about the contrails again, the probability of headache is pretty darn high. Stay safe out there, and Happy Thanksgiving.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Adolescents with migraine need smooth handoff to adult care
, 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.
, 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.
, 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.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Switching Patients From a Triptan to a Gepant for Acute Migraine Care and Effective Preventives
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.
Avoid adding to minority stress when treating headache in LGBTQIA+ patients
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Artificial intelligence presents opportunities, challenges in neurologic practice
PHOENIX –
and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX –
and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX –
and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
AT AANEM 2023