Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events.

BACKGROUND: Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. METHODS: A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. RESULTS: The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05-1.49]; aHR time-varying 8.74 [5.21-14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22-2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26-3.63]). The relative incidence (RI) for all events was 2.13 [1.76-2.58] in the SCCS, for cardiac (RI: 1.67 [1.23-2.27]) and for cerebral events (RI: 3.20, [2.30-4.45]). CONCLUSION: The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.

Risk of Stroke and Myocardial Infarction Among Initiators of Triptans.

Importance: Triptans are contraindicated in patients with ischemic heart disease or previous myocardial infarction, and caution is advised when prescribing these drugs to patients with vascular risk factors. However, controlled observational studies have either shown no association or an apparent lower risk, possibly owing to a channeling of triptans to individuals at low risk of cardiovascular outcomes, and it remains unclear whether avoiding triptan treatment for these patients is meaningful. Objective: To establish whether an association between triptans and ischemic events could be demonstrated using a self-controlled design because this type of design is robust to the previously mentioned type of confounding. Design, Setting, and Participants: All people in nationwide Danish registries who were initiating triptans and all the ischemic events that they experienced were identified. A case-crossover design was used to estimate odds ratios (OR) for associations between first-ever triptan use and ischemic outcomes, comparing triptan exposure in the 2-week period up to the event with four 2-week reference periods. Data were obtained for the period January 1995 to August 2022. Included from the population of Denmark were individuals redeeming a prescription for any triptan and experiencing at least 1 of 3 predefined ischemic outcomes. No one was excluded. Exposure: Initiation of any triptan. Main Outcomes and Measures: Acute myocardial infarction, ischemic stroke, or nonspecified stroke. Results: Identified were a total of 429 612 individuals (median [IQR] age, 38 [28-48] years; 325 687 female [75.8%]) who redeemed a first prescription for a triptan in the study period. Of these patients, 11 (0.003%) had a myocardial infarction with the first triptan prescription in either a focal or referent window (odds ratio [OR], 3.3; 95% CI, 1.0-10.9), 18 (0.004%) had ischemic stroke (OR, 3.2; 95% CI, 1.3-8.1), and 35 (0.008%) had ischemic/nonspecified stroke (OR, 3.0; 95% CI, 1.5-5.9). Case patients had a median age of approximately 60 years and had a high-risk cardiovascular profile. Conclusions and Relevance: Results of this case-crossover study suggest that triptan initiation was associated with higher risk of ischemic stroke and myocardial infarction. For the individual patient with low background cardiovascular risk, the risk of an ischemic event after triptan initiation was very low.

Evidence-based symptomatic treatment of migraine.

Symptomatic treatment of migraine includes patient education, mainly to avoid medication overuse and known trigger factors, as well as pharmaceutical and nonpharmaceutical interventions. Disease-specific and mechanism-based agents include ergotamine and dihydroergotamine targeting the adrenergic, dopaminergic, and serotoninergic systems followed by triptans, specific agonists for 5-HT1B/1D/1F receptors, the latest being more favorable in terms of safety and documentation of efficacy. Recently, antagonists of calcitonin gene-related peptide (gepants) and selective agonists of the 5-HT1F receptor (ditans) have been added, with promising efficacy and safety. Triptans stay as the first option treatment when attacks are moderate to severe, followed by nonspecific agents, including aspirin and paracetamol/acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs, ibuprofen and naproxen share the best documentation) for mild-to-moderate migraine attacks. Combinations with caffeine are effective as well, but barbiturates and opioids alone or in combinations should be avoided. Simple analgesics and NSAIDs attenuate cephalic pain via prostaglandin mediated mechanisms and may induce peptic, renal and hepatic adverse effects. Neuromodulation techniques include single-pulse transcranial magnetic stimulation (s-TMS), external trigeminal nerve stimulation (e-TNS), remote electrical neuromodulation (REN) and noninvasive vagus nerve stimulation (nVNS). All share good documentation and safety profile and are worthy of alternative treatment options along with physical therapy when medicines are contradicted or not well tolerated or unwanted by the patients.

[New therapeutic era for migraine attacks with recently approved monoclonal antibodies, ditans and gepants]. / Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant). Furthermore, eptinezumab, which has been approved for the preventive treatment of migraine in adults, has also been used for migraine attacks. This manuscript reviews the efficacy and safety results of the new drugs for migraines that will soon be on the market.

TITLE: Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.El tratamiento de los ataques de migraña se aconseja en todos los pacientes, utilizando antiinflamatorios no esteroideos cuando el dolor es leve y triptanes cuando la intensidad del dolor es moderada-grave. Sin embargo, la efectividad de estos fármacos es modesta, un porcentaje elevado de pacientes presenta efectos secundarios y los triptanes están contraindicados en las personas con antecedentes de ictus, cardiopatía isquémica o hipertensión mal controlada. Por tanto, es imprescindible disponer de nuevas alternativas terapéuticas. En los últimos años han ido apareciendo nuevos fármacos para los ataques de migraña, entre los que destacan los ditanes (lasmiditán) y los gepantes (ubrogepant y rimegepant). Por otro lado, el eptinezumab, que ha sido aprobado para el tratamiento preventivo de la migraña en adultos, se ha utilizado también para los ataques de migraña. En este manuscrito se revisan los resultados de eficacia y seguridad de los nuevos fármacos para los ataques de migraña que se comercializarán próximamente.

A fatal case of aspiration due to consumption of the hallucinogenic tryptamine derivative dipropyltryptamine (DPT).

BACKGROUND AND AIM: This case involves a 20-year-old man with prior hallucinogen-use experience, who sniffed an unknown amount of dipropyltryptamine in an apartment. Dipropyltryptamine, a hallucinogenic compound belonging to the tryptamine class is recognized for inducing effects similar to dimethyltryptamine (DMT) but with a longer duration. Ten to fifteen minutes later he experienced visual hallucinations, followed by increasing apathy. Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. Despite emergency medical resuscitation on site, transport to hospital 2.5 hours post consumption and extracorporeal life support he died 21 hours later. Relevant toxicological and morphological findings are presented. METHODS: A serum sample was collected four hours post consumption. Autopsy was performed six days after death. Antemortem serum, as well as postmortem cardiac blood and urine were analyzed for alcohol and psychoactive drugs by systematic toxicological analyses employing gas chromatography-mass spectrometry (Maurer/Pfleger/Weber library among others), liquid chromatography-ion trap mass spectrometry (LC-MSn, Toxtyper™), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Dipropyltryptamine was quantified by LC-MS/MS after solid-phase extraction. RESULTS: Autopsy revealed a state after deep aspiration of gastric contents with consecutive brain edema due to oxygen deprivation. Dipropyltryptamine concentrations were approximately 210 ng/ml, 110 ng/ml and 180 ng/ml in antemortem serum, postmortem cardiac blood and urine, respectively. To the best of our knowledge, these are the first reported concentrations of dipropyltryptamine in a fatal case. CONCLUSION: Unlike typical tryptamine overdose reports, this case did not present with agitation, hyperthermia, or tachycardia. Despite the individual's prior experience with tryptamines and the generally low toxicity associated with this class of hallucinogens, death in this case was an indirect consequence of the nasal consumption of a high dose of dipropyltryptamine.

Association Between Migraine and Ischemic Cardio-Cerebrovascular Disease (CCVD) and Effects of Triptans and Ergotamine on the Risk of Ischemic CCVD in Patients with Migraine in the Korean NHIS-HEALS Cohort.

BACKGROUND AND OBJECTIVES: Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs. METHODS: Participants from the Korean NHIS-HEALS cohort database were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared. RESULTS: Among 62,272 patients diagnosed with migraine or HA, men with migraine or HA numbered 14,747 and 8935, respectively, while the numbers of women were 27,836 and 10,754, respectively. The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4728/38,590 (12.25%) in females and 3158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01-1.39) and 1.39 (1.28-1.50), respectively, in males, and 1.22 (1.09-1.37) and 1.53 (1.42-1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73-0.999) in males and 0.80 (0.72-0.88) in females. CONCLUSIONS: Migraine increased the risk of ischemic CCVDs in both sexes, and migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than migraineurs who did not take those medications, especially in women.

What do patients' efficacy and tolerability ratings of acute migraine medication tell us? Cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Most migraine patients need an effective acute medication. Real-world data can provide important information on the performance of acute migraine medication in clinical practice. METHODS: We used data from the German Migraine and Headache Society Headache Registry, where patients rate efficacy and tolerability of and satisfaction with each of their acute headache medications. RESULTS: A total of 1756 adult migraine patients (females: 85%, age: 39.5 ± 12.8 years, headache days per month: 13.5 ± 8.1) were included. Of these, 93% used acute medication, most frequently triptans (59.3%) and/or non-opioid analgesics (56.4%), and 58.5% rated efficacy as good or very good. This was more frequent for triptans (75.4%) than for non-opioid analgesics (43.6%, p < 0.001). Among non-opioid analgesics, naproxen was rated most effective (61.9% very good or good, p < 0.001 compared to ibuprofen, acetylsalicylic acid and paracetamol). Patient-rated efficacy significantly declined with higher headache frequencies (p < 0.001), and this effect remained significant after omitting patients overusing acute medication. CONCLUSION: In the present population recruited at specialized headache centers, patients rated triptans as more effective than non-opioid analgesics, naproxen as more effective than ibuprofen, and acute medication efficacy decreased with increasing headache frequency.Trial registration: The German Migraine and Headache Society Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Utilization patterns, cardiovascular risk, and concomitant serotoninergic medications among triptan users between 2008 and 2018: A gender analysis in one Italian region, Tuscany.

OBJECTIVE: To describe the pattern of triptan use by gender in Tuscany, Italy, focusing on special user populations in which evidence on triptan safety is still not conclusive. BACKGROUND: Growing evidence supports the role of gender differences in migraine pathophysiology and treatment. However, gender impact on triptan real-word utilization has been poorly investigated. METHODS: A retrospective, descriptive, cohort study was performed using the population-based Administrative Healthcare Database of Tuscany region (Italy). Subjects registered in the database on the January 1 of each year between 2008 and 2018 were identified. New users (NU) of triptans (ATC:N02CC*) were patients with one or more triptan dispensation during the year of interest and none in the past. Age, cardiovascular comorbidities representing an absolute or a possible contraindication to triptan utilization, concomitant serotonergic medications, and pattern of triptan use during 1-year follow-up were described by gender. RESULTS: A total of 86,109 patients who received one or more triptan dispensing were identified. Of 64,672 NU (men = 17,039; women = 47,633), 10.2% (6823/64,672) were aged >65 years, who were mostly women (n = 4613). Among NU, men and women with absolute cardiovascular contraindications were 4.3% (740/17,039) and 2.1% (1022/47,633), respectively, while those concomitantly taking serotonergic medications were 17.2% (267/1549) and 21.9% (949/4330), respectively (949/4330). Regular users (two or more dispensing with ≥3 months between first and last observed dispensing) accounted for 26.4% of women (12,597/47,633) and 19.11% of men (3250/17,039); frequent users (≥15 dosage units/month during ≥3 consecutive months) were overall 0.1% (94/64,672) and 62.0% (58/94) of them concomitantly received serotonergic medications. CONCLUSION: Considering gender differences in triptan use highlighted here, large scale observational studies are warranted to better define what populations are safe to use triptans and whether it is appropriate to tighten or relax certain recommendations on triptan use. In the meantime, any suspected adverse drug reaction observed in the special user populations highlighted in this study should be promptly reported.

Onset of Transient Sadness Following the Concomitant Use of a Triptan and Selective Serotonin Reuptake Inhibitor/Serotonin Norepinephrine Reuptake Inhibitors Therapy: A Case Report.

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2-3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome.

Sumatriptan prevents central sensitization specifically in the trigeminal dermatome in humans.

BACKGROUND: The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain. METHODS: Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing. RESULTS: After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome. CONCLUSIONS: Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain. SIGNIFICANCE: Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.

Alopecia signals associated with calcitonin gene-related peptide inhibitors in the treatment or prophylaxis of migraine: A pharmacovigilance study.

STUDY OBJECTIVE: Although rarely observed in clinical trials, alopecia has been reported in migraine patients treated with calcitonin gene-related peptide (CGRP) inhibitors during the postmarketing period. This study sought to assess whether CGRP inhibitors are associated with disproportionate alopecia reporting relative to other drugs including those indicated for migraine treatment or prophylaxis in a real-world setting. DESIGN: Retrospective disproportionality analysis. DATA SOURCE: Spontaneous adverse events reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) through the fourth quarter of 2021. MEASUREMENTS AND MAIN RESULTS: Thirteen Medical Dictionary for Regulatory Activities preferred terms were used to define alopecia cases in FAERS. Disproportionality was measured by calculating proportional reporting ratios (PRR) and 95% confidence intervals (CI). A PRR >2.0 with a lower 95% CI >1.0 and ≥3 cases was considered a positive signal. During the study period, CGRP inhibitors were reported as suspect products in 55,994 adverse events including 1827 (3.26%) alopecia cases. Compared with all other drugs across FAERS, alopecia signals were detected for the collective CGRP inhibitor class (PRR 4.06; 95% CI 3.88-4.25) and fremanezumab (PRR 5.42; 95% CI 4.66-6.29), erenumab (PRR 4.29; 95% CI 4.05-4.54), galcanezumab (PRR 4.11; 95% CI 3.78-4.48), and eptinezumab (PRR 2.06; 95% CI 1.25-3.40) individually. CGRP inhibitors were consistently associated with alopecia signals relative to triptans (PRR 12.46; 95% CI 10.22-15.18) and celecoxib (PRR 3.50; 95% CI 3.19-3.83), but not in comparison with anticonvulsants, onabotulinumtoxinA, or beta-blockers across analyses. Within the CGRP inhibitor class, an alopecia signal was observed for biologics relative to drugs (PRR 6.11; 95% CI 3.79-9.87). CONCLUSION: Significant alopecia signals were identified for CGRP inhibitors relative to all other drugs and certain comparator migraine therapies based on adverse events reported to FAERS, with CGRP-targeting biologics primarily driving disproportionate reporting. Future observational data will be necessary to better characterize the potential association between real-world use of CGRP inhibitors and incident alopecia in patients with migraine.

Potential Channeling Bias in the Evaluation of Cardiovascular Risk: The Importance of Comparator Selection in Observational Research.

BACKGROUND: Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and adverse event risks. It can affect the validity of observational study results, and potentially impact data interpretation, regulatory decision making, and patient medication access. OBJECTIVE: The aim of this study was to assess the impact of comparator selection bias using two real-world case studies evaluating an increased rate of acute myocardial infarction (AMI). METHODS: Data from the Truven Health Analytics MarketScan® electronic medical claims database were used to conduct two retrospective observational cohort studies, utilizing a cohort new-user design, comparing AMI risk between testosterone replacement therapy (TRT) and phosphodiesterase-5 inhibitors (PDE5is) in men treated for hypogonadism, and triptans versus other prescribed acute treatments for migraine in adults. All patients were enrolled continuously in a health plan (no enrollment gap > 31 consecutive days) for ≥ 1 year before index. Baseline period was defined as 365 days prior to index. Exposure was defined by prescription and outcome of interest was defined as occurrence of AMI. Using Cox proportional hazard models, primary analysis for the TRT cohort compared AMI risk between propensity score (PS)-matched TRT-treated and untreated patients; secondary analysis evaluated risk between PS-matched TRT-treated and PDE5i-treated patients. For the triptan cohort, primary analysis compared AMI/ischemic stroke risk between PS-matched triptan-treated and opiate-treated patients; secondary analysis evaluated risk between PS-matched triptan-treated and nonsteroidal anti-inflammatory drug (NSAID)-treated patients and PS-matched non-prescription-treated migraine patients and general patients. RESULTS: No significant association between TRT and AMI was observed among TRT-treated (N = 198,528, mean age 52.4 ± 11.4 years) versus PDE5i-treated men (N = 198,528, mean age 52.3 ± 11.5 years) overall (adjusted hazard ratio [aHR] 1.01; 95% CI 0.95-1.07; p = 0.80). Among patients with prior cardiovascular disease (CVD), risk of AMI was significantly increased for TRT-treated versus PDE5i-treated patients (aHR 1.13; 95% CI 1.03-1.25). The triptan study included three comparisons (triptans [N = 436,642] vs prescription NSAIDs [N = 334,152], opiates [N = 55,234], and untreated migraine [N = 1,168,212]), and a positive control (untreated vs general non-migraine patients [N = 11,735,009]). Analyses of MI risk in migraine patients prescribed triptans versus NSAIDs/opiates had mixed results: the point estimate ranged from 0.33 to 0.84 depending on chosen study window. CONCLUSIONS: Cardiovascular outcomes were not worse in hypogonadism patients with TRT versus PDE5i; however, a potential association with AMI was found in patients with prior CVD receiving TRT versus PDE5i. Findings pointed to a pseudo-protective effect of triptans versus untreated migraine patients or those potentially older and less healthy patients exposed to prescription NSAIDs or opiates. Triptan users should not be compared with those using other anti-migraine prescriptions when evaluating cardiovascular outcomes in migraine patients. Presence of high cardiovascular risks may contribute to channeling bias-healthier subjects being selected to receive treatment-highlighting the importance of choosing comparators wisely in observational studies.

Clinical characteristics of medication-overuse headache according to the class of acute medication: A cross-sectional multicenter study.

OBJECTIVE: To characterize the clinical features of patients with medication-overuse headache (MOH) according to the class of acute medications being overused. BACKGROUND: MOH is a common global health problem, severely disabling the majority of the patients affected. Although various medications can cause MOH, whether clinical features differ according to the overused medication type remains unclear. METHODS: We analyzed data from a multicenter cross-sectional study in neurology clinics in Korea from April 2020 to June 2021. RESULTS: Among 229 eligible patients, MOH was documented in patients who overused multiple drug classes (69/229, 30.1%; most frequent occurrence), triptans (50/229, 21.8%), non-opioid analgesics (48/229, 21.0%), and combination-analgesics (40/229, 17.4%). Patients who overused multiple drug classes reported more frequent use of acute medications (median [25th-75th percentiles]: 25.0 [15.0-30.0] vs. 17.5 [10.0-25.5] days/month, p = 0.029) and fewer crystal-clear days (0.0 [0.0-9.5] vs. 9.0 [0.0-10.0] days/month, p = 0.048) than those who overused triptans. Patients who overused multiple drug classes also reported shorter intervals from chronic daily headache to the onset of MOH than patients who overused combination-analgesics (0.6 [0.2-1.9] vs. 2.4 [0.7-5.4] years, p = 0.001) or non-opioid analgesics (1.5 [0.6-4.3] years, p = 0.004). Patients who overused multiple drug classes reported more emergency room visits (1.0 [0.0-1.0] visits/year) than those who overused combination-analgesics (0.0 [0.0-1.0], p = 0.024) or non-opioid analgesics (0.0 [0.0-1.0], p = 0.030). Patients who overused triptans reported fewer headache days (21.0 [20.0-30.0] vs. 30.0 [20.5-30.0] days/month, p = 0.008) and fewer severe headache days (7.0 [4.0-10.0] vs. 10.0 [5.0-15.0] days/month, p = 0.017) than those who overused non-opioid analgesics. CONCLUSIONS: Some clinical characteristics of MOH significantly differed according to the class of overused medications. The findings from this study may contribute to the understanding of the clinical characteristics and pathophysiology of MOH.

Safety evaluation of oral calcitonin-gene-related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) receptor antagonists have been suggested as novel treatments for acute migraine. This study aimed to use meta-analysis to compare the safety and tolerability of five existing oral CGRP receptor antagonists (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant) with that of a placebo or triptans against acute migraine. METHODS: Five prominent databases were searched to identify randomized controlled trials on this topic. The primary safety outcomes of interest were any adverse events (AEs) and treatment-related adverse events (TRAEs), and secondary outcomes were individual events, namely diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting. RESULTS: Fifteen studies met the eligibility criteria and were examined in detail. Although, compared to placebo, oral CGRP receptor antagonists significantly increased the incidence of any AEs (risk ratio [RR] = 1.15; 95% confidence interval [CI] = 1.07-1.23), there was no difference in the incidence of TRAEs (RR = 1.18; 95% CI = 1.00-1.38). Moreover, CGRP receptor antagonists were safer than triptans with respect to primary safety outcomes, such as any AEs (RR = 0.78; 95% CI = 0.63-0.98) and TRAEs (RR = 0.68; 95% CI = 0.58-0.79). CONCLUSION: Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine.

Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring.

Importance: Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy. Objective: To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring. Design, Setting, and Participants: This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021. Exposure: Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only. Main Outcomes and Measures: An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners' Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs. Results: The ADHD diagnosis sample comprised 10 167 children (mean [SD] maternal age, 30.2 [4.6] years; 5231 boys [51.5%]), and the ADHD symptoms sample comprised 4367 children (mean [SD] maternal age, 30.6 [4.4] years; 2191 boys [50.2%]). Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy (weighted HR, 1.16; 95% CI, 0.78-1.74) and compared with unexposed children whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94). There were no differences in ADHD symptom scores between exposed and unexposed children. Conclusions and Relevance: The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans.

Drug Safety in Episodic Migraine Management in Adults Part 1: Acute Treatments.

PURPOSE OF REVIEW: The aim of this review is to aid in choosing safe options when assessing potential risks of acute migraine treatments based on known mechanisms of action and anticipated safety concerns. RECENT FINDINGS: Part 1 highlights safety issues associated with commonly used medications to treat acute migraine attacks. Strategies to mitigate cardiovascular and gastrointestinal risks of nonsteroidal anti-inflammatory drugs, evaluation of cardiovascular risks of triptan and ergot alkaloids, and precautions with use of antiemetics and the novel drugs gepants and ditans are discussed to help practitioners in clinical decision-making. When available, we included recommendations from professional societies and data from pharmacovigilance systems. While guidelines on efficacy are available, one must also consider the possible risks and adverse effects of a drug when creating treatment plans.