Robertson, Carrie E.

Abstract Objectives/Background Treatment of migraine in the setting of either renal or hepatic disease can be daunting for clinicians. Not only does the method of metabolism have to be considered, but also the method of elimination/excretion of the parent drug and any active or toxic metabolites. Furthermore, it is difficult to think about liver or kidney disease in isolation, as liver disease can sometimes contribute to impaired renal function and renal disease can sometimes impair hepatic metabolism, through the cytochrome P450 system. Methods A detailed search for terms related to liver disease, renal disease, and migraine management was performed in PubMed, Ovid Medline, Embase, and the Cochrane Library.For each medication, product labels were retrieved and reviewed using the US FDA website, with additional review of IBM Micromedex, LiverTox, and the Renal Drug Handbook. Results This manuscript provides an overview of migraine drug metabolism and how it can be affected by liver and renal impairment. It reviews the standard terminology recommended by the US Food and Drug Administration for the different stages of hepatic and renal failure. The available evidence regarding the use of abortive and preventative medicines in the setting of organ failure is discussed in detail, including more recent therapies such as lasmiditan, gepants, and calcitonin gene‐related peptide antibodies. Conclusions For acute therapy, the use of NSAIDS should be limited, as these carry risk for both severe hepatic and renal disease. Triptans can be selectively used, often with dose guideline adjustments. Ubrogepant may be used in severe hepatic disease with dose adjustment and lasmiditan can be used in end stage renal disease. Though non‐medicine strategies may be the most reasonable initial approach, many preventative medications can be used in the setting of hepatic and renal disease, often with dose adjustment. This review provides tables of guidelines, including reduced dosing recommendations, for the use of abortive and preventative migraine medications in hepatic and renal failure.

Abstract OBJECTIVE Using individual pharmacogenomic phenotypes to investigate the factors affecting the efficacy and tolerability of verapamil for migraine prevention. BACKGROUND Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the minimum effective and maximum tolerable verapamil doses for migraine prevention were assessed. RESULTS The mean minimum effective and maximum tolerable doses for the 33 patients in final analysis were 178.2(20–320) mg and 227.9(20–480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.

Abstract Objective To provide an overview of the current available literature on peripheral nerve blocks for the management of migraine and other headache disorders in adults. Background Peripheral nerve blocks have been commonly performed in the headache practice for migraine, cluster headache, occipital neuralgia, and other headache disorders, despite a paucity of evidence supporting their use historically. In the past decade, there has been an effort to explore the efficacy and safety of peripheral nerve blocks for the management of headache, with the greatest interest centered around greater occipital blocks. Design We performed a search in PubMed using key words including “occipital nerve blocks,” “peripheral nerve blocks,” “occipital nerve,” “migraine,” “cluster headache,” and “neuralgia.” We reviewed the randomized controlled trials (RCTs), observational studies, and case series, and summarized the anatomy, techniques, and the evidence for the use of peripheral nerve blocks in different headache disorders, with particular focus on available RCTs. Case reports were included for a detail review of adverse events. Results Of 12 RCTs examining the use of greater occipital nerve blocks for migraine, all but one demonstrate efficacy with reduction in headache frequency, intensity, and/or duration compared to placebo. Studies have not demonstrated a difference in clinical outcomes with the use of corticosteroids for nerve blocks compared to blocks with local anesthetic in the treatment of migraine. There are two RCTs supporting the use of greater occipital blockade for cluster headache, both showing benefit of suboccipitally injected corticosteroid. One RCT suggests benefit of greater occipital nerve blocks for cervicogenic headache. Observational studies and case series/reports show that greater occipital nerve block may be effective in prolonged migraine aura, status migrainosus, post‐dural puncture headache, and occipital neuralgia. Overall, peripheral nerve blocks are well tolerated. Serious side effects are rare but have been reported, including acute cerebellar syndrome and infection. Conclusions Peripheral nerve blocks, especially occipital nerve blocks, are a viable treatment option for migraine and may be helpful in cluster headache as a transitional therapy or rescue therapy. Additional prospective studies are needed to investigate the efficacy and safety of occipital nerve blocks for long‐term migraine prevention, as well as for other headache disorders, such as occipital neuralgia.