Headache & Migraine

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

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

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

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

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

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

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Use of a remote electrical neuromodulation device every other day helped patients significantly reduce the number of migraine days compared with a placebo device, according to recent research published in the journal Headache.

The prospective, randomized, double-blind, placebo-controlled, multicenter trial showed that remote electrical neuromodulation (REN) with Nerivio (Theranica Bio-Electronics Ltd.; Bridgewater, N.J.) found a mean reduction/decrease in the number of migraine days by an average of 4.0 days per month, according to Stewart J. Tepper MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., and colleagues.*

“The statistically significant results were maintained in separate subanalyses of the chronic and episodic subsamples, as well as in the separate subanalyses of participants who used and did not use migraine prophylaxis,” Dr. Tepper and colleagues wrote.

A nonpharmacological alternative

Researchers randomized 248 participants into active and placebo groups, with 95 participants in the active group and 84 participants in the placebo group meeting the criteria for a modified intention-to-treat (mITT) analysis. Most of the participants in the ITT dataset were women (85.9%) with an average age of 41.7 years, and a baseline average of 12.2 migraine days and 15.6 headache days. Overall, 52.4% of participants in the ITT dataset had chronic migraine, 25.0% had migraine with aura, and 41.1% were taking preventative medication.

Dr. Tepper and colleagues followed participants for 4 weeks at baseline for observation followed by 8 weeks of participants using the REN device every other day for 45 minutes, or a placebo device that “produces electrical pulses of the same maximum intensity (34 mA) and overall energy, but with different pulse durations and much lower frequencies compared with the active device.” Participants completed a daily diary where they recorded their symptoms.

Researchers assessed the mean change in number of migraine days per month as a primary outcome, and evaluated participants who experienced episodic and chronic migraines separately in subgroup analyses. Secondary outcome measures included mean change in number of moderate or severe headache days, 50% reduction in mean number of headache days compared with baseline, Headache Impact Test short form (HIT-6) and Migraine Specific Quality of Life Questionnaire (MSQ) Role Function Domain total score mean change at 12 weeks compared with week 1, and reduction in mean number of days taking acute headache or migraine medication.

Participants receiving REN treatment had a significant reduction in mean migraine days per month compared with the placebo group (4.0 days vs. 1.3 days; 95% confidence interval, –3.9 days to –1.5 days; P < .001). In subgroup analyses, a significant reduction in migraine days was seen in participants receiving REN treatment with episodic migraine (3.2 days vs. 1.0 days; P = .003) and chronic migraine (4.7 days vs. 1.6 days; P = .001) compared with placebo.

Dr. Tepper and colleagues found a significant reduction in moderate and/or severe headache days among participants receiving REN treatment compared with placebo (3.8 days vs. 2.2 days; P = .005), a significant reduction in headache days overall compared with placebo (4.5 days vs. 1.8 days; P < .001), a significant percentage of patients who experienced 50% reduction in moderate and/or severe headache days compared with placebo (51.6% vs. 35.7%; P = .033), and a significant reduction in acute medication days compared with placebo (3.5 days vs. 1.4 days; P = .001). Dr. Tepper and colleagues found no serious device-related adverse events in either group.

The researchers noted that REN therapy is a “much-needed nonpharmacological alternative” to other preventive and acute treatments for migraine. “Given the previously well-established clinical efficacy and high safety profile in acute treatment of migraine, REN can cover the entire treatment spectrum of migraine, including both acute and preventive treatments,” they said.

‘A good place to start’

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles; past president of the International Headache Society; and editor-in-chief of Neurology Reviews, said the study was well designed, but acknowledged the 8-week follow-up time for participants as one potential area where he would have wanted to see more data.

As a medical device cleared for use by the Food and Drug Administration for acute treatment of migraine, the REM device also appears to be effective as a migraine preventative based on the results of the study with “virtually no adverse events,” he noted.

“I think this is a great treatment. I think it’s a good place to start,” Dr. Rapoport said. Given the low adverse event rate, he said he would be willing to offer the device to patients as a first option for preventing migraine and either switch to another preventative option or add an additional medication in combination based on how the patient responds. However, at the moment, he noted that this device is not covered by insurance.

Now that a REN device has been shown to work in the acute setting and as a preventative, Dr. Rapoport said he is interested in seeing other devices that have been cleared by the FDA as migraine treatments evaluated in migraine prevention. “I think we need more patients tried on the devices so we get an idea of which ones work acutely, which ones work preventively,” he said.

The authors reported personal and institutional relationships in the form of advisory board positions, consultancies, grants, research principal investigator roles, royalties, speakers bureau positions, and stockholders for a variety of pharmaceutical companies, agencies, and other organizations. Several authors disclosed ties with Theranica, the manufacturer of the REN device used in the study. Dr. Rapoport is editor-in-chief of Neurology Reviews and a consultant for Theranica, but was not involved in studies associated with the REN device.

Correction, 2/10/23: An earlier version of this article misstated the reduction in number of migraine days.

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH.