Headache worsening after treatment with IV dihydroergotamine (DHE) does not predict poor headache outcome in the medium term among patients with chronic migraine, according to research published March 1 in Neurology. Headache exacerbation thus is not a sufficient reason to stop treatment. Instead, neurologists should focus on controlling nausea, which is the most important modifiable factor in achieving a good headache outcome, according to the researchers.

Neurologists have used IV DHE to treat patients with migraine for decades. After receiving this therapy, some patients have transient headache worsening, and this development may be interpreted as a reason to stop the infusions. Michael Eller, MD, Assistant Clinical Professor of Neurology at the University of California, San Francisco (UCSF), and colleagues performed a retrospective chart review to determine whether transient headache worsening after IV DHE infusion predicts medium-term headache outcome in patients with chronic migraine.

The investigators included all patients with chronic migraine admitted by the UCSF Headache Service between January 1, 2008, and December 31, 2012, in their analysis. All patients received IV DHE according to a standard protocol, which included 1-mg doses administered over five days to a typical target dose of 11.25 mg. In addition, patients were premedicated with ondansetron, domperidone, or both. Participants with medication overuse (approximately 30% of the population) also received IV aspirin before receiving IV DHE.

Dr. Eller and colleagues retrospectively analyzed the prospectively collected inpatient headache diaries, progress notes, and discharge summaries. Physicians did not routinely ask patients whether they had headache exacerbation. The researchers defined DHE worsening as headache (typically, exacerbation of the underlying phenotype) or nausea increase within 30 minutes of the infusion. The treating clinician assessed and recorded medium-term headache outcome at follow-up approximately six weeks after discharge.

During the study period, 274 patients with chronic migraine had inpatient treatment with DHE. Mean age was 44, and 77% of the population was female. In all, 153 patients had been receiving migraine preventives. Headache outcome information was available for 214 patients, and patients with missing outcome data did not differ from the others in terms of age, sex, or likelihood of having nausea or medication overuse. Approximately 78% of patients with follow-up data had medium-term headache benefit following IV DHE.

Forty-one participants (19%) had headache worsening with DHE infusions. Of these patients, 66% had medium-term headache benefit, compared with 82% of patients who did not have headache exacerbation. A univariate analysis indicated that headache exacerbation with DHE infusion was associated with reduced odds of medium-term headache benefit. Multivariate logistic regression analysis adjusted for nausea, leg cramping, medication overuse, sex, and age, however, indicated that headache exacerbation with DHE was not an independent predictor of medium-term headache benefit.

Nausea was the modifiable risk factor with the greatest effect on headache outcome. In an adjusted model, nausea was significantly associated with headache exacerbation with DHE infusion. Nausea also was an independent predictor of decreased likelihood of medium-term headache benefit in the fully adjusted model, as was medication overuse. Older age was strongly associated with increased odds of headache benefit.

The results suggest that adequate nausea control might help prevent headache exacerbation, said the authors. “Clinicians in all settings should focus their efforts on aggressive nausea control during a course of IV DHE for chronic migraine,” they added. Younger patients with chronic migraine were less likely to benefit from an inpatient course of IV DHE, and this finding “highlights an even greater need for nausea control in that population.”

The study’s retrospective design was a limitation, said Dr. Eller. Some exacerbations of headache may have gone unreported, and future studies should systematically query patients for this symptom, he added.

Data Improve the Understanding of DHE

The investigation by Dr. Eller and colleagues improves our current understanding of the effects of DHE, said Andrew Charles, MD, Director of the Headache Research and Treatment Program at the University of California, Los Angeles, in an accompanying editorial. The careful documentation and systematic reporting of patient experience, although retrospective, can be valuable in characterizing common patient-management issues, he added.

In population studies, persistent frequent nausea has been associated with increased risk of progression from episodic migraine to chronic migraine. “Whether or not treatment of nausea as a ‘modifiable risk factor’ actually changes the clinical course of migraine remains unclear,” said Dr. Charles. “What is clear, however, is that nausea is a frequently disabling component of migraine that warrants aggressive therapy.” Various therapeutic options exist, but no evidence clearly supports one option over the others. “This study underscores the importance of optimizing therapy of migraine-related nausea, and of coming to a better understanding of the role of nausea and its treatment in the short- and long-term outcomes of patients with migraine,” Dr. Charles concluded.

—Erik Greb

Headache Worsening After IV DHE May Not Predict Outcome of Chronic Migraine