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Botulinum Toxin Type A More Effective and Safer Than Divalproex Sodium for Migraine Prevention: Presented at EFNS

By Chris Berrie

GLASGOW, UK -- September 8, 2006 -- Botulinum toxin type A (BoNTA; Botox) is significantly more effective than, and shows a superior safety and tolerability profile to, divalproex sodium (DVPX; Depakote) for prophylactic treatment of patients with migraine, according to a prospective, randomised, single-centre, evaluator-masked, single-treatment study.

DVPX is approved in the USA for migraine prophylaxis and its primary metabolite, valproic acid, is the recommended first-line agent for migraine prophylaxis in Europe. Botulinum toxin is a novel therapeutic that appears to have a purely peripheral mechanism of action as an inhibitor of neurotransmitter release.

Investigator Jack Schim, MD, codirector, Headache Centre of Southern California, Neurology Center, Oceanside, California, United States, presented the findings of a comparative study of the 2 drugs for prophylactic migraine treatment here on September 4^th at the 10^th Congress of the European Federation of Neurological Societies (EFNS)

They enrolled 60 patients 18 to 65 years of age who had never been treated with either DVPX or BoNTA, and who had 2 to 8 migraine episodes per month and fewer than 15 headache days per month for at least 1 year prior to enrolment. Patient use of migraine prophylaxis and other medication had to be stable for at least 4 weeks.

Exclusion criteria were any medical condition that could potentially cause risks during exposure to DVPX or BoNTA, pregnant or nursing women, and history of complicated migraine (eg, migrainous infarction, hemiplegic migraine, ophthalmoplegic migraine, or basilar migraine) or of acute headache medication overuse (> 15 days per month) or abuse.

The study consisted of a 3-month screening period before randomisation and 3 months of treatment with either DVPX or BoNTA.

The dose of oral DVPX at week 1 was 250 mg twice daily increased to 500 mg thereafter, and increased to 750 mg or decreased to 250 mg at the investigators' discretion. BoNTA injections consisted of a 105- to 260-U dose using a follow-the-pain protocol, administered in the frontal/glabellar, occipitalis, temporalis, trapezius, semispinalis, and splenius capitis areas.

Sixty percent of the DVPX and 100% of the BoNTA patients completed the study (P < .0001).

Patients had a mean age of 41 years and 6.7% were male. There were no significant differences between the treatment groups for baseline and demographic characteristics.

The cohort as a whole had a mean of 4.2 migraine headaches per month, with a mean duration of 34.3 hours per migraine. Severity of headache pain was moderate in 53.3% and severe in 46.7%.

Total scores on the Migraine Disability Assessment Scale (MIDAS) at baseline were 21.6 for the DVPX group and 21.4 for the BoNTA group, indicating severe disability (P = .488). At day 90, the mean change from baseline was -0.27 for DVPX and -8.05 for BoNTA, a significant different in favour of BoNTS (P = .038).

At baseline, the mean number of headaches per 3-month interval were not significantly different between DVPX and BoNTA (14.3 vs 13.8, respectively; P = .440), but at day 90 DVPX showed fewer patients who had a 50% or greater reduction from baseline (10.0% vs 33.3%; P = .0287).

Mean reductions in headache pain as determined with the MIDAS score was significantly greater with BoNTA than with DVPX at all time points (P less than or equal to .04). Migraine Impact Questionnaire (MIQ) scores at day 30 showed fewer DVPX patients compared with BoNTA patients who were satisfied with their treatment's ability to reduce headache frequency (16.7% vs 56.7%;P = .01) and severity (13.3% vs 46.7%; P = .03). At day 60 MIQ scores showed that DVPX patients were less satisfied than BoNTA patients in terms of their treatment's ability to prevent migraine episodes (23.3% vs 46.7%; P = .0006).

Responses to the Patient Satisfaction Questionnaire (PSQ) at day 90 indicated that 80% or more of the patients in each group were satisfied with their treatments (P = .33), although significantly fewer DVPX patients said they would like to continue their study medication compared with the BoNTA group (47.8% vs 83.3%; P = .003).

Safety and tolerability evaluation showed a trend towards more adverse events that were possibly related to DVPX treatment compared with BoNTA (21 vs 9; P = .142). In the DVPX group, these included gastrointestinal (GI)-related events (GI upset, constipation, vomiting), fatigue, weight gain, tremor, depression, insomnia, and dizziness, while in the BoNTA group they included muscle weakness, minor swallowing trouble, neck stiffness, and injection site induration.

Dr. Schim stressed that the nonsystemic nature and preferable dosing regimen of this BoNTA regimen showed that, "In the real world, what this can also be boiled down to is patient preference, where [BoNTA] does not require them to take something every day and to have to deal with the systemic side effects, which is desirable."

This study was sponsored by Allergan.


[Presentation title: Botulinum Toxin Type A Compared With Divalproex Sodium for the Prophylactic Treatment of Migraine: a Randomised, Evaluator-Masked Trial. Abstract P2291]

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