Coenzyme Q10 for migraine prophylaxis.
Coenzyme Q10 is a naturally occurring hydrophobic substance that is involved in electron transfer across the mitochondrial membrane from the NADH dehydrogenase complex and the succinate-Q reductase complex to cytochrome c (Cephalalgia 2002;22:137-41). As such, coenzyme Q10 is essential for cellular energy metabolism.
The coenzyme was first isolated in 1957 from bovine heart mitochondria by Frederick L. Crane, Ph.D., of the University of Wisconsin Enzyme Institute in Madison. A year later, its chemical structure was identified by researchers at Merck Laboratories. In 1978, British scientist Peter D. Mitchell, Ph.D., won the Nobel Prize in chemistry for his work demonstrating the role of coenzyme Q10 in mitochondrial energy transfer.
During the ensuing decades, researchers have investigated potential therapeutic applications for coenzyme Q10 in congestive heart failure, cancer, and neurologic disorders. It has also been studied extensively for use in mitochondrial cytopathies such as Kearns-Sayre syndrome.
The rationale for its use in migraine derives from findings on magnetic resonance spectroscopy and DNA analysis suggesting that mitochondrial dysfunction and inadequate energy production in the brain may be involved in the pathogenesis of migraine.
In an open-label study, 26 women and 6 men with International Headache Society-defined episodic migraine with or without aura were treated with 150 mg of coenzyme Q10 each day for 3 months. Patients began keeping a headache diary 1 month before starting treatment and continued throughout, recording duration of headache, severity, and associated symptoms such as nausea.
The study's primary outcome measure was the percentage of patients who achieved a greater than 50% reduction in the number of days with migraine. A total of 61.3% of patients met that outcome measure by 3 months, and 93.5% had at least a 25% reduction (Cephalalgia 2002;22:137-41).
During the month prior to initiation of treatment, the average number of days with headache was 7.34; this decreased to 2.95 days during the last 2 months of treatment, which is a statistically significant difference.
Attack frequency decreased significantly, from 4.85 during the month prior to treatment to 2.81 during the final 60 days of the study.
Headache intensity did not decrease, and there was no difference in response between patients with and without aura. No adverse events were seen in the study.
Coenzyme Q10 also was evaluated in a double-blind trial that included 42 patients with or without aura. All patients received placebo for 1 month; if they experienced a migraine during that time, they then were randomized to receive placebo or a liquid formulation of coenzyme Q10, 100 mg three times per day, for 3 months. This dose was chosen because it was used previously in a study of patients with Parkinson's disease (Neurology 1998;50:793-5). The primary outcome measure was change from baseline in attack frequency after the 3 months of treatment.
The number of attacks per month was 4.4 at baseline in both the treatment and placebo groups. This number decreased by 0.09 in the placebo group and by 1.19 in the active treatment group, a difference that is statistically significant. There also was a significant continuous decrease in attack frequency between months 1 and 4 in the treatment group (Neurology 2005;64:713-5).
Severity, duration, and acute medication use did not differ between the groups. One patient in the treatment group experienced a cutaneous allergic reaction, but no other adverse events were seen.
The investigators noted that there typically is a lag before significant improvement is seen with coenzyme Q10. "It is conceivable that a clinical effect due to improved mitochondrial function might build up more slowly than one mediated by receptor blockade (for example, [beta]-blockers)," they said.
They also said that the placebo response they found, 14%, was low and reflected the exclusion of four patients who had no headaches during the month-long placebo phase of the study and who might have been placebo responders.
The study was sponsored by MSE Pharmaceuticals, Bad Homburg, Germany, the manufacturer of the liquid formulation of coenzyme Q10 used.
Dr. Alan M. Rapoport, founder and director of the New England Center for Headache, Stamford, Conn., has tried coenzyme Q10 in about 100 migraine patients.
"After the double-blind study was published, I began using it in many of my patients to see if it decreased or prevented migraines. But I tend to not be very scientific with over-the-counter medications, using two or three of them together and possibly in combination with a preventive medication," he said in an interview.
This, of course, makes it difficult to know precisely what is working if the patient does improve.
"I'm just glad they're better," he said. "My feeling is that it does work in some patients to reduce the frequency of headaches, and it doesn't seem to have any side effects," said Dr. Rapoport, who is also a clinical professor of neurology at Columbia University, New York.
His experience has suggested that coenzyme Q10 seems to be most useful in younger patients--those in their teens, 20s, and 30s--and in those who do not have daily, very severe headaches.
He would like to see a larger trial, also double blind and placebo controlled, but for now, he said, he is "cautiously optimistic."
* The dietary supplement coenzyme Q10 is being studied for use in migraine prophylaxis, based on the hypothesis that mitochondrial dysfunction may be involved in the pathogenesis of the disorder.
* A small double-blind trial found significant benefits in reducing the number and frequency of headaches.
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|Title Annotation:||care and treatment|
|Publication:||Clinical Psychiatry News|
|Date:||Mar 1, 2006|
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