Difference of Cerebrospinal Fluid Biomarkers and Neuropsychiatric Symptoms Profiles among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient.

The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-ß42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer's Coordinating Center's Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-ß42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer's disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-ß at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aß-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aß-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer's patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.

A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine.

Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.

Unveiling the age-related dynamics in Sjögren's syndrome: Insights from heart rate variability and autonomic function.

BACKGROUND: Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. METHODS: From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. RESULTS: Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p = .022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p = .041). Age-stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p = .005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p < .001), and significantly lower VAG activity (4.70 ± 1.26, p = .007) compared to healthy controls. Furthermore, the Standard Deviation of Normal-to-Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p = .007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R-wave validity (93.50 ± 4.79, p < .05) than other groups, suggesting more severe autonomic imbalance. The R-R interval variation (RRIV) was also significantly higher in this dual-positive group (696.10 ± 975.41, p < .05). Additionally, the ESSPRI for dryness was markedly higher in the dual-positive group (8.10 ± 1.45, p < .05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual-positive biopsy and autoantibody status. CONCLUSION: This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age-stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age-specific management approaches in pSS patient care.

Update on gepants for the treatment of chronic migraine.

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.

Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.

BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.

Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.

The immediate effects of lavender-based essential oil inhalation on subsequent polysomnography in people with poor sleep quality.

BACKGROUND: Although aromatherapy is considered an adjuvant therapy to promote sleep quality, few objective sleep testing instruments can confirm the effects of aromatherapy on sleep physiology. The purpose of this study was to confirm and compare the immediate effects of a single lavender essential oil (SLEO) group to a complex lavender essential oil (CLEO) group by objective polysomnography (PSG) recordings. METHODS: Participants were randomly divided into the SLEO group and CLEO group in this single-blind trial to explore the sleep effect of essential oil aroma. All the participants completed the sleep-related questionnaires and underwent two consecutive nights of PSG recordings, who had one night without aromatherapy and one night with one of the two aromas randomly assigned to them. RESULTS: Total of 53 participants were recruited for this study, 25 participants were in the SLEO group, and 28 were in the CLEO group. Baseline characteristics and sleep-related questionnaires were similar in both groups. Both SLEO and CLEO extended the total sleep time (TST) (Δ = 43.42 and 23.75 minutes, respectively) and sleep period time (SPT) (Δ = 38.86 and 24.07 minutes, respectively). The SLEO group further improved sleep efficiency and increased the amounts of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and decreased spontaneous arousals. However, there was no significant difference in PSG parameters between the SLEO and CLEO groups. CONCLUSION: Both SLEO and CLEO extended TST and SPT, with no significant differences between these two groups. These results warrant practical applications and merit future studies (Clinical trial registration: ClinicalTrials.gov : NCT03933553).

Renal and survival benefits of seventeen prescribed Chinese herbal medicines against oxidative-inflammatory stress in systemic lupus erythematosus patients with chronic kidney disease: a real-world longitudinal study.

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000-2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia. Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE. Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25-0.79, p = 0.006), all-cause mortality (0.56; 0.43-0.75, p < 0.0001), non-cardiovascular mortality (0.56; 0.42-0.75, p < 0.0001), and hospitalization (0.72; 0.52-0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19-0.95, p = 0.004) for ESRD, 1.22 years (0.63-1.82, p < 0.0001) for all-cause mortality, and 1.21 years (0.62-1.80, p < 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan. Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition.

Associations Between Sarcopenia, Heart Failure and Myocardial Infarction in Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Objectives: To evaluate associations between sarcopenia, type of autoimmune disease and risk of heart failure (HF) and myocardial infarction (MI) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: In this population-based, cross-sectional study, discharge data from the 2005-2014 US Nationwide Inpatient Sample (NIS) of hospitalized patients with SLE or RA were extracted and analyzed. Univariate and multivariable regression analyses were conducted to determine associations between sarcopenia, type of autoimmune disease and risk of HF/MI. Results: After exclusions, 781,199 hospitalized patients diagnosed with SLE or RA were included. Among the study cohort, 127,812 (16.4%) were hospitalized with HF, and 12,781 (1.6%) were hospitalized with MI. Sarcopenia was found in only 0.1% of HF/MI patients. Logistic regression analyses revealed that sarcopenia was not significantly associated with presence of either HF or MI. Patients with RA had significantly lower odds of HF than SLE patients (aOR = 0.77, 95%CI: 0.76, 0.79) or MI (aOR = 0.86, 95%CI: 0.82, 0.91). Conclusion: In the US, among hospitalized adults diagnosed with SLE or RA, patients with RA are significantly less likely to have HF or MI than those with SLE. Whether sarcopenia leads to increased HF or MI remains inconclusive. Further studies are warranted to investigate the pathophysiology underlying discrepancies between RA and SLE regarding risk for MI or HF.

Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.

The effect of bright light therapy in migraine patients with sleep disturbance: A prospective, observational cohort study protocol.

Background: Migraine is a common disabling disorder, and its substantial burden is associated with a considerable negative impact on the patients' quality of life. Moreover, aging patients with migraine have more cognitive complaints. Additionally, the elderly are more likely to have sleep disturbances, which may also predict the risk of incident dementia. Migraines are reported to be closely associated with sleep and circadian rhythms. Sleep disturbance is a well-known trigger for migraine episodes; moreover, shift work or jet lag reportedly triggers some migraines. The hypothalamus is thought to be the migraine generator; sleep and circadian activity rhythm are also controlled by the hypothalamus. Evidence suggests an influence of both sleep and circadian system on migraine. Previously, light therapy has been show to stabilize sleep architecture and further improve insomnia related to circadian rhythm disorders. However, the beneficial effect of light therapy on migraine with sleep disturbance has not yet been determined. We aim to explore the effects of light therapy for migraine combined with sleep disturbance. Methods and analysis: This project is a 2-year, randomized, double-blind, placebo-controlled clinical trial. The study design includes a 4-week monitoring period (baseline and pretest), a 4-week treatment period, and a posttest. The study participants will undergo assessments on headache frequency and severity and subjective and objective (wrist actigraphy and polysomnography) sleep disturbances, and quality of life and a series of blood tests for serum biomarkers. Discussion: This study will establish evidence-based alternative medicine for the preventive effect of bright light therapy in migraine patients with sleep disturbances. Moreover, our data will be useful to comprehend the biochemical mechanism of light therapy in migraine prevention.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04890691.

The effects of acupuncture and related techniques on patients with rheumatoid arthritis: A systematic review and meta-analysis.

BACKGROUND: One new type of acupuncture and related techniques (ACNRT) is increasingly used by rheumatoid arthritis (RA) patients to control their disease and improve their quality of life. However, the efficacy of using ACNRT in combination with western medicine (WM) for this purpose remains unknown. METHODS: Randomized controlled trials of ACNRT and WM treatments for RA from January 1, 2000, to January 31, 2021, were searched for in the databases PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials, as well as in three Chinese databases: China National Knowledge Infrastructure, Wanfang Data, and Airiti Library. The primary outcomes consisted of inflammatory markers including C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor. The secondary outcomes were clinical characteristics including pain visual analog scale (VAS) score, Disease Activity Score (DAS-28), swollen joints count (SJC), tender joints count (TJC), morning stiffness, and the results of a health assessment questionnaire. The three types of ACNRT used in the focal trials were acupuncture, moxibustion, and electro-acupuncture. Two qualified researchers extracted data from these trials' results and independently assessed their risk of bias. Statistical analyses were performed using Comprehensive Meta-Analysis V3 software. RESULTS: A total of 12 RCTs with 874 patients met the inclusion criteria. As compared with the patients who received WM treatment alone, those who were given integrated ACNRT/WM treatment showed greater reductions in CRP (weighted mean difference [WMD]: -6.299; 95% CI: -9.082 to -3.517), ESR (WMD: -6.563; 95% CI: -8.604 to -4.522), VAS (WMD: -1.089; 95% CI: -1.575 to -0.602), DAS-28 (WMD: -0.633; 95% CI: -1.006 to -0.259), SJC (WMD: -1.921; 95% CI: -3.635 to -0.207), and TJC (WMD: -1.491; 95% CI: -2.941 to -0.042). CONCLUSION: This meta-analysis of RA provides reliable evidence in favor of ACNRT plus WM. However, longer term, high-quality, repeatable, multicenter randomized controlled trials with larger sample sizes are needed.

Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis.

Importance: New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant). Objective: To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches. Data Sources: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020. Study Selection: Double-blind randomized clinical trials examining current available migraine-specific acute treatments were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a random-effects model. Main Outcomes and Measures: The primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events. Results: A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin gene-related peptide antagonists. Conclusions and Relevance: For pain freedom or pain relief at 2 hours after the dose, lasmiditan, rimegepant, and ubrogepant were associated with higher ORs compared with placebo but lower ORs compared with most triptans. However, the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.