Lu AG0922
Lu AG09222 is an investigational humanized monoclonal antibody which targets pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP is located in sensory nerve fibers and infusion of PACAP induces a migraine.[210]Guo S, Jansen-Olesen I, Olesen J, et al. Role of PACAP in migraine: an alternative to CGRP? Neurobiol Dis. 2023 Jan;176:105946.
https://www.sciencedirect.com/science/article/pii/S0969996122003382?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/36481434?tool=bestpractice.com
In a phase 2, double-blind randomized controlled trial, a single infusion of Lu AG09222 reduced migraine frequency by an additional 2 days over the subsequent 4 weeks, compared with placebo. Adverse events were more common in the LU AG09222 group and included nasopharyngitis and fatigue.[211]Ashina M, Phul R, Khodaie M, et al. A monoclonal antibody to PACAP for migraine prevention. N Engl J Med. 2024 Sep 5;391(9):800-9.
http://www.ncbi.nlm.nih.gov/pubmed/39231342?tool=bestpractice.com
Melatonin
Pineal gland irregularity has been suggested as a cause of migraine, and its hormone, melatonin, has been found to be low in patients with migraine. Abnormal melatonin secretion may be a marker of a more general neurologic disorder, or may affect calcitonin gene-related peptide (CGRP) regulation. There is some evidence that melatonin is effective for migraine prevention, with few adverse effects, but high-quality studies are required.[212]Puliappadamb HM, Maiti R, Mishra A, et al. Efficacy and safety of melatonin as prophylaxis for migraine in adults: a meta-analysis. J Oral Facial Pain Headache. 2022 Summer;36(3-4):207-19.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10586587
http://www.ncbi.nlm.nih.gov/pubmed/36445912?tool=bestpractice.com
Larger clinical trials are needed to determine the efficacy of melatonin.
Greater occipital nerve block or ablation
Systematic reviews have concluded that greater occipital nerve block significantly reduces pain intensity, migraine frequency, and analgesic use in patients with migraine compared with placebo.[213]Velásquez-Rimachi V, Chachaima-Mar J, Cárdenas-Baltazar EC, et al. Greater occipital nerve block for chronic migraine patients: A meta-analysis. Acta Neurol Scand. 2022 Aug;146(2):101-14.
http://www.ncbi.nlm.nih.gov/pubmed/35726455?tool=bestpractice.com
[214]Barad M, Ailani J, Hakim SM, et al. Percutaneous interventional strategies for migraine prevention: a systematic review and practice guideline. Pain Med. 2022 Jan 3;23(1):164-88.
https://academic.oup.com/painmedicine/article/23/1/164/6348178?login=false
http://www.ncbi.nlm.nih.gov/pubmed/34382092?tool=bestpractice.com
Levetiracetam
There is some evidence from randomized controlled trials that the anticonvulsant levetiracetam is associated with decreased migraine frequency and severity, compared with placebo.[215]Yen PH, Kuan YC, Tam KW, et al. Efficacy of levetiracetam for migraine prophylaxis: a systematic review and meta-analysis. J Formos Med Assoc. 2021 Jan;120(1 pt 3):755-64.
https://pdf.sciencedirectassets.com/276220/1-s2.0-S0929664620X00167/1-s2.0-S0929664620303946/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEL3%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJHMEUCIA4t6gXfvKViR7sRUkACrG9NSMZkg76hnv9fCmwOkUvHAiEA0cRbAAB3zeaRgcfzLFqIpPz5asVe7IgaOOwD0vdkovsqvAUI9v%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARAFGgwwNTkwMDM1NDY4NjUiDFkR%2FtQA4%2BDaJGS0miqQBSWaolFBKI2edv1r072DRqaTyPR8u%2FxVo9kH12UF3cprCgD4PW%2FGvGg3%2FpL3CCHRbdMy2hGHgMeyJeBjXk%2FjIKvO1VPV2rDNFE6IwxJ1%2Bj%2F%2Bat7Fds9OXFZ%2FmsKEv%2Fkmqm9wR%2BDs1J%2FoDW6kzXFlze%2B2lfYJeGoKblr5ZZz7At%2BLYseDvc8ituGinaqtbwx1zl%2BJzovARhetGZZ4SbhExslfrJC7tHbf%2Bd%2BdDsqSsXv351i0Pfp6XFva47uJjAvVr5bQooWlX2LLri27dDxcLrbz85hiOULbVrD6iDNQDjj%2FVaQ8i0PnaO2hXpdMEE72Dej5pBRXDQrZgJtTxRmzizuXRLu15ckPzMVjW7eU%2FgmEgt4QEMgaXbffV0Fvd3CyUsLxxyt6VSm%2BAQ0QkErMvli6plcwe9R%2FOcnca6hyHUj1VkKEy2genRDzoXxZgMyfY1DTOX5RCU5DP2xotajpVWNQZGFM%2B3IjE5KopnhvVqw%2FlDr5E5exLDWAA%2FNphPI12ePkxzmSFAVJYDGf57Ahkt8%2BY4wHkl3vqhzNcpqy%2B8FmaKpW7CUiaYInv%2BYiexHXVL2CHijuFRCL8H4Wq1DPpB80CgmJZx7YlcOgQm1MALFeYIXgBcnuEYJR%2BN1YXQp0LXDYSb4dxj9t7lqUoo%2BC2KczvG9sACi%2FXNLFEuwghhpl3CmR8SqE8acIC8PeetYylEnBEFtMIWxY9QH7uY%2F9lxN6mRwMWDW5vi%2F1SwWUYB8k6wq%2Bf2SJO99xom0wI0kmRIEG2yeO7xV%2FH3EL2lXEbqHPvcNKT%2F3vqZ2udkCPNM77pnW%2FJo95YX4m8wQS8CcUUKpw77Qmlios5AkTUr8z5rA0pZEogUAr7zXvnXUZGxpQMPDGnb4GOrEBjcyq%2F3sGRPb9F6JH94Fn3hhejP1O%2FZRRxFXMXPir%2FIYP1X37e4n9MOeUvbvLFLKAA7%2F9qsy7cv%2FagkfxOSL1lCS1ua7fN678z1iehNoKWQ69xQEVuDxeHUJUNhknZIxm1Gd20DcDRfwB1g3Wro58I06nocy5UPEqJ%2F%2B1z%2BEGnNaR3bXZgUJ0gbw%2Bm7w8e9fnxvdbrGqrheQ3ZsshOilJv2HHXIBl6BbwAkHc%2FRA06NEB&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250304T213931Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTY33BHI6YZ%2F20250304%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=9c70499f6c37f2a1d36dadc2dfe42e328ebabd6365ea1fdff69028b6ebe6a101&hash=435c17027bdeb655869a4b37df65e35ce01912f8397aaa9ddcf59afae94c6b72&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0929664620303946&tid=spdf-e9ba1766-068a-4d96-b5f3-be7bbb07e7fa&sid=d24844b727e8a54e0359b2f769f2b22b01dagxrqb&type=client&tsoh=d3d3LnNjaWVuY2VkaXJlY3QuY29t&rh=d3d3LnNjaWVuY2VkaXJlY3QuY29t&ua=0c085d530d555f510454&rr=91b486d3ede08e80&cc=in
http://www.ncbi.nlm.nih.gov/pubmed/32861551?tool=bestpractice.com
Zonisamide
One randomized controlled trial has compared the efficacy of anticonvulsant zonisamide with topiramate for migraine prophylaxis. Zonisamide was as effective as topiramate for reducing headache frequency, severity, disability, and need for acute medication.[216]Mohammadianinejad SE, Abbasi V, Sajedi SA, et al. Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial. Clin Neuropharmacol. 2011 Jul-Aug;34(4):174-7.
http://www.ncbi.nlm.nih.gov/pubmed/21738025?tool=bestpractice.com