Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine

The purpose of this study is to compare valproic acid (VPA) and dihydroergotamine (DHE) alone
and sequentially in the treatment of pediatric migraines.

Inpatient pediatric migraine patients (based on International Classification of Headache
Disorders, ICHD-II criteria) or those admitted to the University of Kentucky emergency
department will receive standard of care acute headache management as per AAP/AAN guidelines.
Those who fail to respond will be considered for further eligibility. Informed consent/assent
will be obtained from the patients, parents or legal guardian.

Baseline labs will be collected prior to the start of the study.

1. Complete Blood Count (CBC)

2. Comprehensive Metabolic Panel (CMP)

3. Prothrombin Time/Activated Partial Thromboplastin Time/International Normalized Ratio
(PT/APTT/INR)

4. Magnesium and phosphorous

Patients will initially be randomized into two groups (VPA or DHE) and treated for 24 hours.
Those patients whose migraines resolve will end the study at 24 hours. Patients who are
refractory to treatment will switch interventions and continue treatment for an additional 24
hours.

Intervention 1: VPA Intervention 2: DHE

Patients in Group 1 will be treated with VPA for 24 hours. They will be given an initial dose
of IV VPA at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum
levels of VPA will be checked at 4 and 24 hours; depending on drug levels they may also be
checked at 8 and 12 hours. The target serum concentration is 100 (+/-10) ug/mL.

Patients in Group 2 will be treated with DHE for 24 hours. Dosing will be weight-based with
no single dose >1mg and total 24 hour dose <3mg.

0 hour: 0.5 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.0
x (wt in kg) x (0.014) =Xmg

Patients will be assessed for migraine severity at baseline, 4, 8, 12, and 24 hours.

1. pain (using the standard 0-10 point VAS pain scale)

2. presence or absence of photophobia

3. presence or absence of phonophobia

4. presence or absence of nausea

The endpoint criterion is successful migraine resolution (improvement in VAS and resolution
of photophobia, phonophobia, and nausea). Patients meeting this criterion will not continue
forward in the study.

At 24 hours, those patients that are refractory to treatment will cross over to the alternate
intervention, i.e. patients receiving VPA first will then get DHE, and patients receiving DHE
first will then get VPA. Outcomes will be measured for the next 24 hour period as described
above.

Inclusion Criteria:

- acute migraine as per ICHD-II criteria

- pediatric (age 10-18)

Exclusion Criteria:

For Valproic Acid (VPA)

- Pregnancy

- Liver disease (Acute or Chronic)

- Urea Cycle Disorder

- Mitochondrial Disease

For Dihydroergotamine (DHE)

- Pregnancy

- Peripheral vascular disease, coronary heart disease

- History of cerebrovascular event

- Severe or poorly controlled hypertension

- Impaired liver or renal function

- Triptan given in last 24 hours

- Hemiplegic migraine