Background: Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods: A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results: We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion: Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression. Genotyping for the two variants within the FKBP5 gene was performed using PCR-restriction fragment length polymorphism and Taqman real-time PCR in a cohort of 179 inpatients who were monitored for the first 3 weeks of antidepressant drug treatment. The early response to antidepressant drugs was assessed as percentage of decline in Hamilton depression score after 3 weeks, responders versus nonresponders were distinguished by a 50% decrease. The FKBP5 variants rs3800373 and rs1360780 were highly linked, and carriers of the FKBP5 variants had a trend towards a higher chance to respond (p = 0.04; odds ratio: 1.8; 95% CI: 0.98-3.3). When analyzing drug-specific subgroups, the effect was seen mainly in the subgroups of patients treated with antidepressant drug combinations or with venlafaxine. In this study, an effect of FKBP5 variants on antidepressant drug response was confirmed in an independent cohort of depressed patients; however, with an odds ratio of 1.8 the effect size was smaller than that described earlier.

ICHD-3 criteria for chronic migraine (CM) include a mixture of migraine and tension-type-like headaches and do not account for patients who have a high frequency of migraine but no other headaches. Patients from the Danish Headache Center and their relatives with ICHD-3 defined CM were compared with patients with high frequency episodic migraine (HFEM). Danish registries were used to compare the socioeconomic impact in these two groups. A Russian student population was used to determine the generalizability of the number of patients fulfilling CM and the proposed diagnostic criteria for CM. There was no difference in the demographic profile between the two groups in the Danish cohort. The number of lifelong or annual attacks (p > 0.3), comorbid diseases, or self-reported effect of triptans (p = 1) did not differ. HFEM patients purchased more triptans than CM patients (p = 0.01). CM patients received more early pension (p = 0.00135) but did not differ from HFEM patients with regard to sickness benefit (p = 0.207), cash assistance (p = 0.139), or rehabilitation benefit (p = 1). Patients with HFEM are comparable to CM patients with regard to chronicity and disability. We therefore suggest classifying CM as ≥ 8 migraine days per month (proposed CM), disregarding the need for ≥ 15 headache days per month. The proposed diagnostic criteria for CM approximately doubled the number of patients with CM in both the Danish and the Russian materials. Extending the definition of CM to include patients with HFEM will ensure that patients with significant disease burden and unmet treatment needs are identified and provided appropriate access to the range of treatment options and resources available to those with CM. Patients with migraine on eight or more days but not 15 days with headache a month are as disabled as patients with ICHD-3 defined CM. They should be included in revised diagnostic criteria for chronic migraine.

Background: The diagnosis of transient ischemic attacks is fraught with problems. The inter-observer agreement has repeatedly been shown to be low even in a neurological setting, and the specificity of the diagnosis is modest to low, reflected in a poor separation of transient ischemic attacks and mimics, particularly migraine with aura with its varied symptomatology. In other disease areas, explicit diagnostic criteria have improved sensitivity and specificity of diagnoses. We therefore present novel explicit diagnostic criteria for transient ischemic attacks tested for sensitivity and for specificity against migraine with aura. Methods: The proposed criteria were developed using the format of the international headache classification. We drew upon the existing literature about clinical characteristics and diagnosis of migraine with aura and transient ischemic attacks. We tested the criteria for sensitivity in a prospectively-collected material of 120 patients with transient ischemic attacks diagnosed before we developed the criteria using extensive semi-structured interview forms in the acute phase after admission. Eligible patients had focal brain or retinal ischemia with resolution of symptoms within 24 hours without presence of new infarction on magnetic resonance imaging with diffusion weighted imaging (n = 112) or computed tomography (n = 8). These criteria were also tested for specificity against a Danish (n = 1390) and a Russian (n = 152) material of patients with migraine with aura diagnosed according to the International Classification of Headache Disorders edition 3 (beta). Results: The sensitivity of the proposed criteria was 99% in patients with transient ischemic attacks. The specificity was 95% in the Danish material of patients with migraine with aura and 96% in the Russian material. Conclusions: Proposed explicit diagnostic criteria for transient ischemic attacks showed both high specificity and sensitivity. They are likely to improve the emergency room diagnosis of transient ischemic attacks. Further testing in unselected materials referred to transient ischemic attacks clinics was beyond the scope of the present study but is recommended for future study.

Background: In our previous study of workers, blood donors and medical students, students stood out with a higher 1-year prevalence of migraine (28%) and tension-type headache (TTH) (74%). General factors associated with headache were common for all groups except low physical activity. The hypothesis of this study was therefore that a number of psychosocial factors relating to the personal sphere would better explain the high prevalence of migraine and TTH in students. Methods: The study population consisted of 1042 students (719 females, 323 males, mean age 20.6, range 17–40). Headache diagnoses and associated factors were identified by direct professional semi-structured interview. We also interviewed about the following psychosocial factors: dissatisfaction with study, dissatisfaction with family life, dissatisfaction for personal reasons, bad financial situation, overwork, stress, not enough sleep, insomnia, depressed mood, anxiety, irritability, tendency towards conflicts and not being married. We report psychosocial factors associated with headache according to diagnosis and sex using univariate and multivariate logistic regression analyses. Results: Several factors were significantly associated with migraine and TTH in the univariate analysis. In the multivariate analysis, two psychosocial factors were statistically significantly associated with migraine in all students: irritability (OR 2.2, 95% CI 1.4–3.6) and overwork (OR 2.2, 95% CI 1.4–3.5). Insomnia (2.7, 95% CI 1.1–6.9) and depressed mood (OR 2.1, 95% CI 1.1–4.2) were associated with migraine only in females. Two psychosocial factors were associated with TTH: dissatisfaction with study in males (OR 2.0, 95% CI 1.0–3.8) and depressed mood in females (OR 1.8, 95% CI 1.0–3.5). Conclusion: Psychosocial factors from the personal sphere showed significant association with migraine and TTH in students. Such factors should therefore be major targets for preventive efforts to reduce the prevalence of primary headache disorders in students.

Rupture of a saccular intracranial aneurysm (SIA) causes thunderclap headache but it remains unclear whether headache in general and migraine in particular are more prevalent in patients with unruptured SIA. In a prospective case–control study 199 consecutive patients with SIA (103 females and 96 males, mean age: 43.2 years) received a semistructured face to face interview focusing on past headaches. All were admitted to hospital mostly because of rupture (177) or for unruptured aneurysm (22). In parallel we interviewed 194 blood donors (86 females, 108 males, mean age: 38.4 years). Diagnoses were made according to the International Headache Society criteria. Aneurysms were diagnosed by conventional cerebral angiography. During the year before rupture, 124 (62.3%) had one or more types of headache. These headaches included: migraine without aura (MO): 78 (39.2%), migraine with aura (MA): 2 (1%), probable migraine (PM): 4 (2%), tension-type headache (TTH): 39 (19.6%), cluster headache (CH): 2 (1%), posttraumatic headaches (PH): 2 (1%). 1-year prevalence of headaches in controls was 32.5% (63 patients out of 194), they included: TTH: 45 (23.1%), MO: 17(8.8%), PH: 1(0.5%). Only the prevalence of MO was significantly higher in patients with SIA (OR 6.7, 95% CI 3.8-11.9, p < 0.0001). Unruptured SIA cause a marked increase in the prevalence of migraine without aura but not in the prevalence of other types of headache.