Migraine ICYMI

Key clinical point: Higher body mass index (BMI) was positively associated with an increased risk for medication-overuse headache (MOH) in patients with migraine.

Major finding: Higher BMI was positively associated with a higher risk for MOH (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.11; P = .031), with the risk being significantly higher in patients with migraine who had a BMI ≥ 28.0 kg/m² vs those with BMI of 18.5-23.9 kg/m² (aOR 1.81; 95% CI 1.04-3.17; P = .037).

Study details: This secondary analysis of the Survey of Fibromyalgia Comorbidity with Headache study included 2251 patients with migraine, of whom 195 (8.7%) had concomitant MOH.

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

Source: Liu H, Zhao H, Liu K, et al. Association between body mass index and medication-overuse headache among individuals with migraine: A cross-sectional study. Obes Facts. 2024 (Apr 3). doi: 10.1159/000538528 Source

Key clinical point: Higher body mass index (BMI) was positively associated with an increased risk for medication-overuse headache (MOH) in patients with migraine.

Major finding: Higher BMI was positively associated with a higher risk for MOH (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.11; P = .031), with the risk being significantly higher in patients with migraine who had a BMI ≥ 28.0 kg/m² vs those with BMI of 18.5-23.9 kg/m² (aOR 1.81; 95% CI 1.04-3.17; P = .037).

Study details: This secondary analysis of the Survey of Fibromyalgia Comorbidity with Headache study included 2251 patients with migraine, of whom 195 (8.7%) had concomitant MOH.

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

Source: Liu H, Zhao H, Liu K, et al. Association between body mass index and medication-overuse headache among individuals with migraine: A cross-sectional study. Obes Facts. 2024 (Apr 3). doi: 10.1159/000538528 Source

Key clinical point: Higher body mass index (BMI) was positively associated with an increased risk for medication-overuse headache (MOH) in patients with migraine.

Major finding: Higher BMI was positively associated with a higher risk for MOH (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.11; P = .031), with the risk being significantly higher in patients with migraine who had a BMI ≥ 28.0 kg/m² vs those with BMI of 18.5-23.9 kg/m² (aOR 1.81; 95% CI 1.04-3.17; P = .037).

Study details: This secondary analysis of the Survey of Fibromyalgia Comorbidity with Headache study included 2251 patients with migraine, of whom 195 (8.7%) had concomitant MOH.

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

Source: Liu H, Zhao H, Liu K, et al. Association between body mass index and medication-overuse headache among individuals with migraine: A cross-sectional study. Obes Facts. 2024 (Apr 3). doi: 10.1159/000538528 Source

Key clinical point: A higher dietary phytochemical index (DPI) score is associated with lower migraine frequency and improved migraine-related disability in patients with migraine.

Major finding: Patients with migraine in the third vs first tertile of the DPI showed a significant reduction in migraine frequency (incidence rate ratio 0.84; P_trend= .009) and an improvement in migraine-related disability (β −2.48; P_trend = .046). However, no significant association was seen between DPI and headache duration (P_trend = .439), headache severity (P_trend = .239), depression (P_trend = .480), anxiety (P_trend = .655), and stress (P_trend = .876).

Study details: This cross-sectional study evaluated the association between DPI and the clinical and psychological characteristics of migraine headaches in 262 patients with migraine (age 20-50 years).

Disclosures: This study was supported by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflicts of interest.

Source: Amani Tirani S, Balali A, Kazemi M, et al. The predictive role of the dietary phytochemical index in relation to the clinical and psychological traits of migraine headaches. Sci Rep. 2024;14:6886 (Mar 22). doi: 10.1038/s41598-024-57536-7 Source

Key clinical point: A higher dietary phytochemical index (DPI) score is associated with lower migraine frequency and improved migraine-related disability in patients with migraine.

Major finding: Patients with migraine in the third vs first tertile of the DPI showed a significant reduction in migraine frequency (incidence rate ratio 0.84; P_trend= .009) and an improvement in migraine-related disability (β −2.48; P_trend = .046). However, no significant association was seen between DPI and headache duration (P_trend = .439), headache severity (P_trend = .239), depression (P_trend = .480), anxiety (P_trend = .655), and stress (P_trend = .876).

Study details: This cross-sectional study evaluated the association between DPI and the clinical and psychological characteristics of migraine headaches in 262 patients with migraine (age 20-50 years).

Disclosures: This study was supported by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflicts of interest.

Source: Amani Tirani S, Balali A, Kazemi M, et al. The predictive role of the dietary phytochemical index in relation to the clinical and psychological traits of migraine headaches. Sci Rep. 2024;14:6886 (Mar 22). doi: 10.1038/s41598-024-57536-7 Source

Key clinical point: A higher dietary phytochemical index (DPI) score is associated with lower migraine frequency and improved migraine-related disability in patients with migraine.

Major finding: Patients with migraine in the third vs first tertile of the DPI showed a significant reduction in migraine frequency (incidence rate ratio 0.84; P_trend= .009) and an improvement in migraine-related disability (β −2.48; P_trend = .046). However, no significant association was seen between DPI and headache duration (P_trend = .439), headache severity (P_trend = .239), depression (P_trend = .480), anxiety (P_trend = .655), and stress (P_trend = .876).

Study details: This cross-sectional study evaluated the association between DPI and the clinical and psychological characteristics of migraine headaches in 262 patients with migraine (age 20-50 years).

Disclosures: This study was supported by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflicts of interest.

Source: Amani Tirani S, Balali A, Kazemi M, et al. The predictive role of the dietary phytochemical index in relation to the clinical and psychological traits of migraine headaches. Sci Rep. 2024;14:6886 (Mar 22). doi: 10.1038/s41598-024-57536-7 Source

Key clinical point: Atopic dermatitis (AD) is significantly associated with a higher risk for headache disorders or migraine.

Major finding: Patients with AD had a significantly higher risk for headache disorder (odds ratio [OR] 1.46; 95% CI 1.36-1.56) or migraine (OR 1.32; 95% CI 1.18-1.47; both P < .001). This finding was consistent across the different subgroup analyses.

Study details: The data come from a meta-analysis of 10 observational studies that evaluated the risk for headache disorders in 12,717,747 patients with AD, of which six studies evaluated migraine risk in 11,090,412 patients with AD.

Disclosures: This study was supported by the project of training talent for Zhejiang province young and middle-aged clinical traditional Chinese medicine experts and Hangzhou Municipal Health and Family Planning Commission Science and Technology Project, China. The authors declared no conflicts of interest.

Source: Yang W, Dai H, Xu X-F, et al. Association of atopic dermatitis and headache disorder: A systematic review and meta-analyses. Front Neurol. 2024;15:1383832. doi: 10.3389/fneur.2024.1383832 Source

Key clinical point: Atopic dermatitis (AD) is significantly associated with a higher risk for headache disorders or migraine.

Major finding: Patients with AD had a significantly higher risk for headache disorder (odds ratio [OR] 1.46; 95% CI 1.36-1.56) or migraine (OR 1.32; 95% CI 1.18-1.47; both P < .001). This finding was consistent across the different subgroup analyses.

Study details: The data come from a meta-analysis of 10 observational studies that evaluated the risk for headache disorders in 12,717,747 patients with AD, of which six studies evaluated migraine risk in 11,090,412 patients with AD.

Disclosures: This study was supported by the project of training talent for Zhejiang province young and middle-aged clinical traditional Chinese medicine experts and Hangzhou Municipal Health and Family Planning Commission Science and Technology Project, China. The authors declared no conflicts of interest.

Source: Yang W, Dai H, Xu X-F, et al. Association of atopic dermatitis and headache disorder: A systematic review and meta-analyses. Front Neurol. 2024;15:1383832. doi: 10.3389/fneur.2024.1383832 Source

Key clinical point: Atopic dermatitis (AD) is significantly associated with a higher risk for headache disorders or migraine.

Major finding: Patients with AD had a significantly higher risk for headache disorder (odds ratio [OR] 1.46; 95% CI 1.36-1.56) or migraine (OR 1.32; 95% CI 1.18-1.47; both P < .001). This finding was consistent across the different subgroup analyses.

Study details: The data come from a meta-analysis of 10 observational studies that evaluated the risk for headache disorders in 12,717,747 patients with AD, of which six studies evaluated migraine risk in 11,090,412 patients with AD.

Disclosures: This study was supported by the project of training talent for Zhejiang province young and middle-aged clinical traditional Chinese medicine experts and Hangzhou Municipal Health and Family Planning Commission Science and Technology Project, China. The authors declared no conflicts of interest.

Source: Yang W, Dai H, Xu X-F, et al. Association of atopic dermatitis and headache disorder: A systematic review and meta-analyses. Front Neurol. 2024;15:1383832. doi: 10.3389/fneur.2024.1383832 Source

Key clinical point: Patients with chronic kidney disease (CKD), particularly older adults and women, had a modestly reduced risk of developing migraine over a 16-year follow-up period.

Major finding: During the 16-year follow-up, patients with vs without CKD had an 11% lower risk for migraine (adjusted hazard ratio [aHR] 0.89; P = .006), with the risk being prominently lower among older adults (age ≥ 70 years; aHR 0.69; P < .001) and women (aHR 0.84; P = .006).

Study details: This nationwide, 16-year longitudinal follow-up study included 15,443 participants with CKD, of whom 349 (2.26%) had migraine, and 61,772 participants without CKD, of whom 1901 (3.08%) had migraine.

Disclosures: This study was supported by Bracco Imaging Korea and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Kwon MJ, Kim J-K, Kim M-J, et al. Associations between chronic kidney disease and migraine incidence: Findings from a Korean longitudinal big data study. J Pers Med. 2024;14(4):356 (Mar 28).  doi: 10.3390/jpm14040356 Source

Key clinical point: Patients with chronic kidney disease (CKD), particularly older adults and women, had a modestly reduced risk of developing migraine over a 16-year follow-up period.

Major finding: During the 16-year follow-up, patients with vs without CKD had an 11% lower risk for migraine (adjusted hazard ratio [aHR] 0.89; P = .006), with the risk being prominently lower among older adults (age ≥ 70 years; aHR 0.69; P < .001) and women (aHR 0.84; P = .006).

Study details: This nationwide, 16-year longitudinal follow-up study included 15,443 participants with CKD, of whom 349 (2.26%) had migraine, and 61,772 participants without CKD, of whom 1901 (3.08%) had migraine.

Disclosures: This study was supported by Bracco Imaging Korea and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Kwon MJ, Kim J-K, Kim M-J, et al. Associations between chronic kidney disease and migraine incidence: Findings from a Korean longitudinal big data study. J Pers Med. 2024;14(4):356 (Mar 28).  doi: 10.3390/jpm14040356 Source

Key clinical point: Patients with chronic kidney disease (CKD), particularly older adults and women, had a modestly reduced risk of developing migraine over a 16-year follow-up period.

Major finding: During the 16-year follow-up, patients with vs without CKD had an 11% lower risk for migraine (adjusted hazard ratio [aHR] 0.89; P = .006), with the risk being prominently lower among older adults (age ≥ 70 years; aHR 0.69; P < .001) and women (aHR 0.84; P = .006).

Study details: This nationwide, 16-year longitudinal follow-up study included 15,443 participants with CKD, of whom 349 (2.26%) had migraine, and 61,772 participants without CKD, of whom 1901 (3.08%) had migraine.

Disclosures: This study was supported by Bracco Imaging Korea and the National Research Foundation of Korea. The authors declared no conflicts of interest.

Source: Kwon MJ, Kim J-K, Kim M-J, et al. Associations between chronic kidney disease and migraine incidence: Findings from a Korean longitudinal big data study. J Pers Med. 2024;14(4):356 (Mar 28).  doi: 10.3390/jpm14040356 Source

Key clinical point: In patients with migraine, any oral prophylactic therapy significantly improved sleep quality, but anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) had significantly better effects than other oral prophylactic therapies.

Major finding: The Pittsburgh Sleep Quality Index (PSQI) score significantly reduced from 6.84 at baseline to 5.581 at 3 months with any oral prophylactic therapy and from 8.913 at baseline to 6.491 at 3 months with anti-CGRP mAbs. Among oral therapies, calcium channel blockers (P = .042) and antidepressants (P = .049) showed higher efficacy in reducing PSQI scores.

Study details: This multicenter prospective study included 214 patients with migraine, with or without aura, who received any oral prophylactic therapy (n = 143) or anti-CGRP mAb (n = 71).

Disclosures: This study was partially supported by Fondazione Giorgini, Italy. Mauro Silvestrini declared receiving financial support from the Giorgini Foundation. The other authors declared no conflicts of interest.

Source: Viticchi G, Di Stefano V, Altamura C, et al. Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study. Sleep Med. 2024;117:87-94 (Mar 17). doi: 10.1016/j.sleep.2024.03.026 Source

Key clinical point: In patients with migraine, any oral prophylactic therapy significantly improved sleep quality, but anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) had significantly better effects than other oral prophylactic therapies.

Major finding: The Pittsburgh Sleep Quality Index (PSQI) score significantly reduced from 6.84 at baseline to 5.581 at 3 months with any oral prophylactic therapy and from 8.913 at baseline to 6.491 at 3 months with anti-CGRP mAbs. Among oral therapies, calcium channel blockers (P = .042) and antidepressants (P = .049) showed higher efficacy in reducing PSQI scores.

Study details: This multicenter prospective study included 214 patients with migraine, with or without aura, who received any oral prophylactic therapy (n = 143) or anti-CGRP mAb (n = 71).

Disclosures: This study was partially supported by Fondazione Giorgini, Italy. Mauro Silvestrini declared receiving financial support from the Giorgini Foundation. The other authors declared no conflicts of interest.

Source: Viticchi G, Di Stefano V, Altamura C, et al. Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study. Sleep Med. 2024;117:87-94 (Mar 17). doi: 10.1016/j.sleep.2024.03.026 Source

Key clinical point: In patients with migraine, any oral prophylactic therapy significantly improved sleep quality, but anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) had significantly better effects than other oral prophylactic therapies.

Major finding: The Pittsburgh Sleep Quality Index (PSQI) score significantly reduced from 6.84 at baseline to 5.581 at 3 months with any oral prophylactic therapy and from 8.913 at baseline to 6.491 at 3 months with anti-CGRP mAbs. Among oral therapies, calcium channel blockers (P = .042) and antidepressants (P = .049) showed higher efficacy in reducing PSQI scores.

Study details: This multicenter prospective study included 214 patients with migraine, with or without aura, who received any oral prophylactic therapy (n = 143) or anti-CGRP mAb (n = 71).

Disclosures: This study was partially supported by Fondazione Giorgini, Italy. Mauro Silvestrini declared receiving financial support from the Giorgini Foundation. The other authors declared no conflicts of interest.

Source: Viticchi G, Di Stefano V, Altamura C, et al. Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study. Sleep Med. 2024;117:87-94 (Mar 17). doi: 10.1016/j.sleep.2024.03.026 Source

Key clinical point: Early initiation of erenumab demonstrated better long-term efficacy, tolerability, and patient adherence than non-specific oral migraine preventive medications (OMPM) in patients with episodic migraine (EM) and one or two previous preventive treatment failures.

Major finding: At month 12, significantly more patients in the erenumab vs OMPM group completed the initially assigned treatment and also achieved a ≥50% reduction in monthly migraine days (odds ratio 6.48; P < .001). A smaller proportion of patients in the erenumab group vs the OMPM group switched medications (2.2% vs 34.6%) and discontinued treatment due to adverse events (2.9% vs 23.3%).

Study details: Findings are from the APPRAISE trial that included 621 patients with EM (age ≥ 18 years) who had previously failed 1 or 2 preventive treatments and were randomly assigned to receive erenumab (n = 413) and OMPM (n = 208).

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Several authors declared themselves as employees of or holding stocks in Novartis, and the other authors declared ties with various sources, including Novartis.

Source: Pozo-Rosich P, Dolezil D, Paemeleire K, et al. Early use of erenumab vs nonspecific oral migraine preventives: The APPRAISE randomized clinical trial. JAMA Neurol. 2024 (Mar 25). doi: 10.1001/jamaneurol.2024.0368 Source

Key clinical point: Early initiation of erenumab demonstrated better long-term efficacy, tolerability, and patient adherence than non-specific oral migraine preventive medications (OMPM) in patients with episodic migraine (EM) and one or two previous preventive treatment failures.

Major finding: At month 12, significantly more patients in the erenumab vs OMPM group completed the initially assigned treatment and also achieved a ≥50% reduction in monthly migraine days (odds ratio 6.48; P < .001). A smaller proportion of patients in the erenumab group vs the OMPM group switched medications (2.2% vs 34.6%) and discontinued treatment due to adverse events (2.9% vs 23.3%).

Study details: Findings are from the APPRAISE trial that included 621 patients with EM (age ≥ 18 years) who had previously failed 1 or 2 preventive treatments and were randomly assigned to receive erenumab (n = 413) and OMPM (n = 208).

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Several authors declared themselves as employees of or holding stocks in Novartis, and the other authors declared ties with various sources, including Novartis.

Source: Pozo-Rosich P, Dolezil D, Paemeleire K, et al. Early use of erenumab vs nonspecific oral migraine preventives: The APPRAISE randomized clinical trial. JAMA Neurol. 2024 (Mar 25). doi: 10.1001/jamaneurol.2024.0368 Source

Key clinical point: Early initiation of erenumab demonstrated better long-term efficacy, tolerability, and patient adherence than non-specific oral migraine preventive medications (OMPM) in patients with episodic migraine (EM) and one or two previous preventive treatment failures.

Major finding: At month 12, significantly more patients in the erenumab vs OMPM group completed the initially assigned treatment and also achieved a ≥50% reduction in monthly migraine days (odds ratio 6.48; P < .001). A smaller proportion of patients in the erenumab group vs the OMPM group switched medications (2.2% vs 34.6%) and discontinued treatment due to adverse events (2.9% vs 23.3%).

Study details: Findings are from the APPRAISE trial that included 621 patients with EM (age ≥ 18 years) who had previously failed 1 or 2 preventive treatments and were randomly assigned to receive erenumab (n = 413) and OMPM (n = 208).

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Several authors declared themselves as employees of or holding stocks in Novartis, and the other authors declared ties with various sources, including Novartis.

Source: Pozo-Rosich P, Dolezil D, Paemeleire K, et al. Early use of erenumab vs nonspecific oral migraine preventives: The APPRAISE randomized clinical trial. JAMA Neurol. 2024 (Mar 25). doi: 10.1001/jamaneurol.2024.0368 Source

Key clinical point: High-dose eicosapentaenoic acid (EPA) monotherapy for 12 weeks showed superior efficacy, safety, and tolerability in patients with episodic migraine (EM), emphasizing its potential as a promising prophylactic option for managing EM.

Major finding: At 12 weeks, EPA vs placebo significantly improved monthly migraine frequency (P = .001), frequency of acute headache medication usage (P = .035), and headache severity (P = .030). No serious adverse events (AE) were reported, and no patients discontinued treatment due to intolerable AE.

Study details: This 12-week randomized, double-blind, placebo-controlled clinical trial included 70 patients with EM who were randomly assigned to receive high-dose EPA (1800 mg/day; n = 70) or placebo (n = 70).

Disclosures: This study was supported by grants from Kuang Tien General Hospital, the Ministry of Science and Technology, the National Science and Technology Council (NSTC) in Taiwan, and others. The authors declared no conflicts of interest.

Source: Wang H-F, Liu W-C, Zailani H, et al. A 12-week randomized, double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine. Brain Behav Immun. 2024;18:459-467 (Mar 16). doi: 10.1016/j.bbi.2024.03.019 Source

Key clinical point: High-dose eicosapentaenoic acid (EPA) monotherapy for 12 weeks showed superior efficacy, safety, and tolerability in patients with episodic migraine (EM), emphasizing its potential as a promising prophylactic option for managing EM.

Major finding: At 12 weeks, EPA vs placebo significantly improved monthly migraine frequency (P = .001), frequency of acute headache medication usage (P = .035), and headache severity (P = .030). No serious adverse events (AE) were reported, and no patients discontinued treatment due to intolerable AE.

Study details: This 12-week randomized, double-blind, placebo-controlled clinical trial included 70 patients with EM who were randomly assigned to receive high-dose EPA (1800 mg/day; n = 70) or placebo (n = 70).

Disclosures: This study was supported by grants from Kuang Tien General Hospital, the Ministry of Science and Technology, the National Science and Technology Council (NSTC) in Taiwan, and others. The authors declared no conflicts of interest.

Source: Wang H-F, Liu W-C, Zailani H, et al. A 12-week randomized, double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine. Brain Behav Immun. 2024;18:459-467 (Mar 16). doi: 10.1016/j.bbi.2024.03.019 Source

Key clinical point: High-dose eicosapentaenoic acid (EPA) monotherapy for 12 weeks showed superior efficacy, safety, and tolerability in patients with episodic migraine (EM), emphasizing its potential as a promising prophylactic option for managing EM.

Major finding: At 12 weeks, EPA vs placebo significantly improved monthly migraine frequency (P = .001), frequency of acute headache medication usage (P = .035), and headache severity (P = .030). No serious adverse events (AE) were reported, and no patients discontinued treatment due to intolerable AE.

Study details: This 12-week randomized, double-blind, placebo-controlled clinical trial included 70 patients with EM who were randomly assigned to receive high-dose EPA (1800 mg/day; n = 70) or placebo (n = 70).

Disclosures: This study was supported by grants from Kuang Tien General Hospital, the Ministry of Science and Technology, the National Science and Technology Council (NSTC) in Taiwan, and others. The authors declared no conflicts of interest.

Source: Wang H-F, Liu W-C, Zailani H, et al. A 12-week randomized, double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine. Brain Behav Immun. 2024;18:459-467 (Mar 16). doi: 10.1016/j.bbi.2024.03.019 Source

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Vaporized cannabis containing tetrahydrocannabinol (THC) and cannabidiol (CBD) may provide rapid and sustained relief of acute migraine pain with no serious side effects, new research suggests. 

“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine. 

The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said. 

He presented the results at the 2024 annual meeting of the American Academy of Neurology. 
 

Sustained Pain Relief

Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking. 

The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.

Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.

The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.

Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.

The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.

The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. 

There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said. 

Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted. 

Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
 

Cautious Optimism

Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”

“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.

“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned. 

He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”

“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said. 

Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”

This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.

A version of this article appeared on Medscape.com.

DENVER — Vaporized cannabis containing tetrahydrocannabinol (THC) and cannabidiol (CBD) may provide rapid and sustained relief of acute migraine pain with no serious side effects, new research suggests. 

“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine. 

The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said. 

He presented the results at the 2024 annual meeting of the American Academy of Neurology. 
 

Sustained Pain Relief

Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking. 

The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.

Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.

The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.

Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.

The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.

The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. 

There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said. 

Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted. 

Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
 

Cautious Optimism

Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”

“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.

“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned. 

He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”

“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said. 

Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”

This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.

A version of this article appeared on Medscape.com.

DENVER — Vaporized cannabis containing tetrahydrocannabinol (THC) and cannabidiol (CBD) may provide rapid and sustained relief of acute migraine pain with no serious side effects, new research suggests. 

“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine. 

The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said. 

He presented the results at the 2024 annual meeting of the American Academy of Neurology. 
 

Sustained Pain Relief

Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking. 

The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.

Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.

The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.

Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.

The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.

The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. 

There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said. 

Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted. 

Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
 

Cautious Optimism

Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”

“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.

“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned. 

He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”

“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said. 

Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”

This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.