Intravenous Treatment of Headache at Outpatient Infusion Centers

Headaches are a common condition affecting an estimated 1 billion people worldwide,¹ and they can be debilitating, especially migraines and cluster headaches. In the United States alone, the American Migraine Foundation estimates that over 39 million people suffer from headache conditions.¹ When over-the-counter pain medications and prescription treatments fail to provide adequate relief, providers have increasingly turned to intravenous (IV) infusion therapy as a treatment option. This shift is due in part to the growing use of biologic treatments for migraine as well as therapies that target calcitonin gene-related peptide (CGRP).

Headache pathophysiology is complex and multifactorial, involving neuroinflammatory cascades, vasodilation, and central sensitization. These mechanisms result in a constellation of symptoms that significantly impact patients’ quality of life. The bioavailability of medications administered directly to the bloodstream offers rapid relief and a more effective response with potential for long-term efficacy. Importantly, infusion protocols can be individualized based on headache subtype, patient history, and response to previous treatments. For patients with chronic daily headache, status migrainosus, cluster headaches, or refractory migraine, IV infusion therapy may provide sustained relief and reduce attack frequency.

Current Infusion Therapy Options

Infusion therapy can be safely administered in a range of settings including hospital emergency departments (EDs), hospital-based infusion units, ambulatory infusion centers, outpatient headache centers, and, in rare cases, even at home administered with visiting nurses. Outpatient centers represent a cost-effective alternative to ED visits, where care is often focused on ruling out secondary causes of headache such as subarachnoid hemorrhage, neoplasm, meningitis, or traumatic brain injury. ED visits typically involve extensive diagnostic workups including but not limited to neuroimaging (ie, CT, MRI, angiography) and lumbar puncture, which can delay treatment and incur significant healthcare costs.^2,3,4,5 Most academic settings offer infusion therapy for refractory headaches because these treatments are essential for patients who are unresponsive to standard medications, but outpatient infusion centers have proven vital in establishing an open-access care model. In some cases, same-day access to infusion therapy—with flexible drug options to break the migraine cycle—has become a cornerstone of effective care delivery.

Despite increasing clinical use of IV therapy for headache management outside hospital settings, there is a notable lack of literature specifically examining the safety, efficacy, and implementation of outpatient IV treatments for primary headache disorders. Most available research stems from emergency or inpatient settings. Outpatient infusion therapy remains underrepresented in scientific publications, with available studies often being retrospective with small sample sizes or part of broader treatment protocols that do not isolate the effects of IV therapy administered outside hospitals. Randomized controlled trials and large-scale prospective studies in this area remain scarce.

The lack of high-quality data presents challenges for evidence-based decision making in outpatient headache medicine. It also hinders the development of standardized protocols, insurance policy guidelines, and best practice recommendations tailored to outpatient infusion use.

Infusion Medications for the Intravenous Treatment of Headache

More than 20 IV medications are used in acute and prophylactic headache treatment.² These include IV valproate sodium, magnesium sulfate, lidocaine, dihydroergotamine (DHE), prochlorperazine, dexamethasone, eptinezumab (Vyepti; Lundbeck, Deerfield, IL), levetiracetam, ketamine, chlorpromazine, metoclopramide, droperidol, methylprednisolone, ketorolac, ondansetron, and diphenhydramine (Table). Providers may use a combination of these medications depending on a patient’s specific needs and prior treatment responses. For patients undergoing CGRP-targeting therapy, administration every 90 days has demonstrated efficacy in preventing migraine onset.

Many institutions have also developed their own “migraine cocktails” for refractory migraines. These typically involve 3 to 4 medications with formulations varying by institution as well as provider. As there is no standardized migraine cocktail, each plan is tailored to the patient’s individual needs. Medication combinations are often modified to address factors such as allergies, age, time constraints for infusion, potential side effects, drug interactions, sedation concerns, and the patient’s ability to drive postinfusion. Additionally, staff education on recognizing and responding to patient reactions such as rashes, nausea, mood changes, and cardiac irregularities is critical for safe and effective infusion treatment.

When prescribing infusion therapy, several factors must be considered. For example, infusion run time is important; too many medications can result in infusion times of several hours, which may be uncomfortable for patients and potentially costly to the practice. Past adverse reactions to medications should also be considered; using one medication to counteract the side effects of another may not be ideal or comfortable. It’s also essential to consider the required frequency of infusions; certain medications (eg, steroids, ketorolac) can be harmful if administered too frequently. Infusions should not be a frequent treatment, especially when medications carry the risk of serious side effects.

Benefits of the Outpatient Infusion Center

Outpatient infusion centers offer an alternative to costly ER visits, where headache remains the fourth most common reason for patients to present.^1,2,4 These centers, staffed by providers who are experienced in headache care, deliver goal-directed treatment while avoiding lengthy triage times, unnecessary procedures (eg, imaging, EKGs, lab work), and reducing the potential for misdiagnosis through subspecialty expertise. They also help in avoiding inappropriate treatments such as narcotics and opioids, which can worsen headaches.² Outpatient centers typically have lower overhead than hospitals, and the bulk purchasing of medications such as magnesium sulfate, ketorolac, and DHE can help to reduce costs. Furthermore, these facilities enable the adjustment of staffing based on demand and can incorporate medications used to treat other conditions (eg, rheumatology, Alzheimer disease and dementia, demyelinating disorders, etc) into their offerings to maintain and in many cases increase profitability. Outpatient centers also offer low-cost, same-day headache cocktails that are covered by most insurance plans without prior authorization, making them a convenient and affordable option.

To further enhance financial performance, many private neurology groups with infusion centers have joined Group Purchasing Organizations (GPOs), a small number of which are neurology focused (eg, NeuroNet GPO).²¹ Membership in GPOs enables practices to secure more favorable pricing on pharmaceuticals and medical supplies through the collective bargaining power of member sites. In addition to cost savings, GPOs facilitate collaboration among member practices to evaluate national reimbursement trends and advocate for improved insurance coverage. This strategic approach improves access to affordable outpatient treatments while supporting the long-term sustainability and independence of private practices.

Additionally, access to treatment is essential for improving patient outcomes and reducing overall burden on the healthcare system. IV infusion therapy at an outpatient facility provides continuity of care, offering patients a reliable treatment option.⁴ This reliability, in turn, can increase patient compliance—patients can trust their treatment plan to prevent and manage migraines. Clinical oversight in outpatient infusion centers also plays a significant role in optimizing outcomes by allowing providers to monitor response, adjust therapy as needed, and provide ongoing support. Furthermore, in addition to avoiding the financial impact of missed diagnosis or misdiagnosis, the expertise available in a dedicated outpatient infusion center can improve the headache treatment experience for patients and their families. The misdiagnosis of headache disorders as stroke or anxiety can be particularly emotionally taxing. 

There is growing literature supporting IV infusion for headache treatment in pediatric and adolescent patients. Over the last several decades, the incidence rate of primary headache disorders among pediatric patients has grown to an estimated 7 million individuals in the United States.²² By extension, this figure suggests a significant increase in disability and reduced quality of life among the pediatric population. Studies suggest that IV treatment for refractory migraine can reduce symptoms and prevent unnecessary ER visits for pediatric patients. An approach that includes medications like DHE and magnesium sulfate has been shown to alleviate symptoms and reduce utilization of healthcare resources.⁵

Potential Challenges of Outpatient Infusion Centers

Outpatient infusion centers and infusion centers more broadly are not without their challenges. One of the most notable is the initial capital investment required to establish an infusion center.  This upfront expense varies based on the size and scope of services offered. This expense could deter some practices from pursuing this ancillary service. In addition to the capital costs, staffing requirements must be carefully considered. Many states impose strict provider-to-patient ratios which differ based on the class of medications being infused. In addition, ensuring appropriate referral patterns to the center is paramount to maintaining profitability. Financial stability of the infusion center is dependent on a consistent and reliable patient population. Another critical factor for the success of infusion centers is the need to operate within a “buy and bill” environment. This reimbursement model presents unique challenges which require oversight, expertise, and infrastructure to manage effectively. Lastly, it is essential for infusion center providers to possess a comprehensive understanding of payer authorization and reimbursement policies. Navigating these policies often involves proactive engagement and, at times, direct negotiation to secure appropriate reimbursement levels.

Conclusion

The economic impact of migraines in the United States is significant, with estimates placing the annual cost burden exceeding $36 billion in direct medical costs as well as indirect costs such as lost productivity, absenteeism, and presenteeism.²³ Given the high cost of migraines, infusion therapy offers a cost-effective solution by reducing the need for frequent ER visits, minimizing hospitalizations, and improving patient outcomes, ultimately helping to reduce the overall economic burden. For independent practices, outpatient infusion centers serve as an ancillary revenue stream, which can also expand to other indications, further enhancing practice independence and offering more options for headache clinicians and patients alike.⁴

IV infusion therapy offers numerous benefits for both patients and healthcare providers. With the ability to deliver fast, targeted treatment in a variety of settings, IV infusions provide an effective solution for managing refractory migraines and improving quality of life. By considering patient-specific factors and fostering a calm, supportive environment, healthcare providers can optimize outcomes, improve compliance, reduce healthcare spending, and enhance the clinical experience for both patients and clinicians.