Dihydroergotamine Infusion for Pediatric Refractory Headache

A Retrospective Chart Review

Rasha Srouji DNP RN, CPNP, CNRN; Sara R. Schenkel MPH; Peter Forbes MA; Jennifer E. Cahill PhD, RN


Headache. 2021;61(5):777-789. 

In This Article

Abstract and Introduction


Background: Headaches are a common symptom in children. Children with refractory headaches may be admitted for inpatient treatment with intravenous dihydroergotamine mesylate (DHE). However, very few studies have characterized these patients and their treatment outcomes using validated, self-reported, pain scales.

Objective: The objective of this study was to describe demographic and clinical characteristics of children admitted for DHE infusion, determine DHE treatment outcomes by means of numeric pain scale ratings, and explore associations between treatment outcomes and clinical characteristics.

Methods: Retrospective chart review was completed in patients ages 5–21 admitted for DHE infusion from January 2013 to July 2018 at a large, pediatric academic medical center and community-based satellite center. All primary headache types were included.

Results: A total of 200 unique admissions for DHE were available for analysis. Overall, patients were predominantly White (87.5%, 175/200) and female (80.0%, 160/200) with an average age of 15.4 years (SD 2.3). Common comorbidities included obesity (42.0%, 81/193), anxiety (41.0%, 82/200), and depression (20.0%, 40/200). The mean length of stay was 2.4 days (SD 1.10; range 1–8 days). Most headaches (65.0%, 130/200) met the International Classification of Headache Disorders, 3rd edition criteria for migraine, followed by new daily persistent headache (25.5%, 51/200). Mean DHE maximum dose was 5.3 (SD 2.17; range 0.5–14.5 mg) with most patients requiring 3.5–6.5 mg. DHE was typically terminated at six doses (range 1–15). The most frequently reported adverse event was nausea (5.5%, 11/200). There was no difference in pain severity at admission across headache types, with an average baseline pain score of 8.1 (SD 1.6). Posttreatment reduction in pain score was statistically significant (range: −3.2 to −4.9; each p < 0.001) across all headache types. Overall, 84.0% (168/200) of the patients had some improvement in pain. More than half of the patients (53.5%, 107/200) showed at least moderate improvement (≥50.0% reduction in pain score), and 18.0% (36/200) had full headache resolution. Limited patients (16.0%, 32/200) experienced no improvement in pain.

Conclusions Treatment with DHE resulted in at least some improvement for most patients regardless of headache type or number of doses. Clinical trials stratified by headache type and comorbid factors could help clarify treatment algorithms to optimize patient outcomes.


Headaches are the most common referral to neurology practices worldwide.[1] The prevalence of pediatric primary headaches is reported to be as high as 58.4%[2] with up to 25% developing chronic recurrent headaches.[3] Previous research supports that the prevalence and clinical presentation of primary headaches vary according to patient characteristics such as age, sex, associated diagnoses, and comorbid conditions. In children, clinical presentations differ and often lack the classic features that define most adult headache syndromes.[4]

Sex differences in headache are more prominent after 12 years of age (puberty) with girls having a higher prevalence than boys (27.4% vs. 20.0%)[5] and reporting more functional disability.[6] Primary headaches in children are commonly associated with other psychiatric and medical comorbidities, including depression, anxiety,[7] obesity,[8] and other chronic pain syndromes,[7] which can influence occurrence, transformation, maintenance, and treatment of headaches in this patient population. It is fundamental to adequately identify comorbidities to establish the correct diagnosis and the most effective treatment strategy.

Primary headache treatment is usually managed in an outpatient setting once an appropriate diagnosis is established. There are some patients, however, who fail to respond to outpatient treatment or have lingering disability/symptom severity and for whom inpatient admission and escalation of therapy may be more appropriate.[9] Admission rates for all pediatric headache types have steadily increased by as much as 300% (2020 in 2003 vs. 8087 in 2013).[10] From 2003 to 2009, there were 11,696 hospitalizations for pediatric migraine, the most common primary headache disorder in childhood and adolescence.[11]

One of the most common medications used for refractory migraine is intravenous (IV) dihydroergotamine (DHE), which typically requires at least a 2-day admission.[9] DHE is an ergot alkaloid synthetized from ergotamine tartrate. Its therapeutic influence is assumed to result from binding serotonin (5-hydroxytryptamine) receptors type 1D and 1B, causing vasoconstriction of vessels and inhibition of the trigeminal release of inflammatory peptides.[12,13] Given the potential side effects from its vasoconstrictive properties, DHE is seldom given as frontline therapy.[14]

Despite the persistence of DHE as a headache treatment (initial FDA approval in 1946), only a limited number of studies have examined the characteristics of, and outcomes for, children prescribed this medication.[15] The repeated IV DHE dose protocol first introduced by Raskin in 1986 has shown some efficacy with migraine headache specifically.[16] Linder (1994) reported an 80% response rate in children who received DHE for migraine with minimal adverse effects.[17] Another study by Kabbouche et al. noted a response rate of 77% in children with status migrainosus.[18] Given the limited availability of second-line headache therapies for children, the decision to admit and initiate DHE is largely driven by the provider, rather than protocol, and may be tried for other refractory headache types per provider discretion. Understanding this broader utilization of DHE may help inform a base of evidence to create better clinical algorithms to direct its use.

There are even fewer data delineating which patients benefit more from inpatient treatment versus the convenience of outpatient infusion centers. These knowledge gaps are important given the current trend of expanding therapies traditionally provisioned in the inpatient setting to more ambulatory-based care centers. As with most diagnoses, it is essential to match the intensity of service to the severity of illness. Yet there are lingering questions about optimal treatment setting and outcomes of children prescribed DHE that challenge the high cost of inpatient care.[9]

Therefore, the purpose of this exploratory, retrospective chart review was twofold:

  1. To describe the demographic and clinical characteristics of pediatric patients with refractory headache admitted for treatment with IV DHE at a large pediatric academic medical center and an affiliated satellite center.

  2. To determine DHE treatment outcomes stratified by headache types, by means of numeric pain scale ratings, and explore associations between treatment settings, outcomes, and clinical characteristics.

The study focused specifically on acute therapy with DHE during the hospital stay and was a preliminary evaluation of the effectiveness of inpatient therapy of headaches. The results will further facilitate the feasibility of expanding our acute service to an outpatient infusion center. Our institution admits patients for IV DHE across all refractory headache types. We hypothesized that DHE treatment outcomes (change in pain) would differ across headache types but not clinical settings.