A total of seven RCTs involving 7266 patients were included. In general, the new drugs demonstrated better result in all the efficacy parameters. The adverse events were observed in treatment group compared to placebo. While in the indirect comparison, lasmiditan emerged to be superior in all the outcomes, except for sustained pain freedom 2-24 h (rimegepant was better). The adverse events were more with lasmiditan. All the newer drugs have shown significant improvement in the outcomes analyzed. Lasmiditan appears to be superior among the newer drugs in efficacy; however it has more adverse effects.All the newer drugs have shown significant improvement in the outcomes analyzed. Lasmiditan appears to be superior among the newer drugs in efficacy; however it has more adverse effects. Migraine is the most prevalent neurological disorder and the leading cause of disability in individuals under 50 years of age. Two types of migraine therapies have been defined acute therapy (abortive or symptomatic treatment), the purpose of which is to interrupt migraine attacks, and preventive treatment (prophylactic treatment), the purpose of which is to reduce the frequency and severity of migraine attacks. This paper reviews research advances in new agents for acute therapy of migraine. This review provides an overview of emerging new drugs for acute treatment of migraine based on clinical evidence and summarizes the milestones of different stages of clinical development. Two new formulations of sumatriptan, DFN-11 (3 mg doses of subcutaneous sumatriptan) and DFN-02 (a nasal spray of sumatriptan 10 mg and a permeation-enhancing excipient), have been developed, and both of them showed a fast-onset action with efficacy for acute treatment of migraine with fewer adverse events. New drug discovery p Disability from migraine has a profound impact on the world's economy. Research has been ongoing to identify biomarkers to aid in diagnosis and treatment. The aim of this study was to highlight the purported diagnostic and therapeutic migraine biomarkers and their role in precision medicine. A comprehensive literature search was conducted using PubMed, Google Scholar, and clinicaltrials.gov using keywords "migraine" OR "headache" combined with "biomarkers" OR "marker." Other keywords included "serum," "cerebral spinal fluid," "inflammatory," and "neuroimaging." After a review of 88 papers, we find the literature supports numerous biomarkers in the diagnosis of migraine. Therapeutic biomarkers, while not as extensively published, highlight calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP-38) as biomarkers with the most substantiated clinical relevance. Genetic markers mainly focusing on gene mutations with resultant biochemical alterations continue to be studied and show promise. Although there are several proposed biomarkers for migraine, continued research is needed to substantiate their role in clinical practice.Although there are several proposed biomarkers for migraine, continued research is needed to substantiate their role in clinical practice. Key structures for the pathophysiology of primary headache disorders such as migraine, cluster headache, and other trigeminal autonomic cephalalgias were identified by imaging in the past years. Available data on functional imaging in primary headache disorders are summarized in this review. We performed a MEDLINE search on December 27 , 2020 using the search terms "primary headache" AND "imaging" that returned 453 results in English, out of which 137 were labeled reviews. click here All articles were evaluated for content and relevance for this narrative review. The structure depicted most consistently using functional imaging in different states of primary headaches (without and with pain) was the posterior hypothalamus. Whole-brain imaging techniques such as resting-state functional resonance imaging showed a wide-ranging association of cortical and subcortical areas with human nociceptive processing in the pathophysiological mechanisms underlying the different TACs. Similarities of distinct groups of primary headache disorders, as well as their differences in brain activation across these disorders, were highlighted. The importance of neuroimaging research from clinical practice point of view remains the reliable and objective distinction of each individual pain syndrome from one another. This will help to make the correct clinical diagnosis and pave the way for better and effective treatment in the future. More research will be necessary to fulfill this unmet need.The importance of neuroimaging research from clinical practice point of view remains the reliable and objective distinction of each individual pain syndrome from one another. This will help to make the correct clinical diagnosis and pave the way for better and effective treatment in the future. More research will be necessary to fulfill this unmet need.Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. The aim of this study was to document epidemiological and economic burden due to headache globally and in India and suggest a public health approach to address headache disorders for India. We reviewed the available literature on burden due to headache, its management using a primary health care approach and health system barriers, with special emphasis on India. Globally, it has been estimated that prevalence of current headache disorder (symptomatic within last year) among adults is about 50%, around 30% report migraine and headache on 15 or more days every month affects 1.7-4% people. The Global Burden of Disease Study 2016 estimated that migraine caused 45·1 million (95% UI 29·0-62·8) and tension-type headache 7·2 million (95% UI 4·6-10·5) years of life lived with disability. Limited data available in India support such high burden. These studies also indicate high diagnostic and treatment gaps for headache disorders in India. Major challenges in addressing headache disorders effectively in India are low perceived severity, absence of burden data, lack of standard treatment protocols for headache disorders and primary care models for neurological disorders in developing country context. There needs to be a better appreciation of the burden and a public health approach among all stakeholders, if burden of headache disorders is to be addressed effectively in India.