Divalproex, Valproate, & Developing Treatment Options for Cluster Headache Prophylaxis: Clinical Practice Considerations

Regarding the preventive treatment of CH, there are few placebo-controlled studies, meaning most treatment recommendations by physicians are limited to results from open observational studies. Additionally, existing effective therapies are believed to be underused because of our underdiagnosis of CH syndrome. Numerous treatment methods are available for different CH attack stages, making them difficult to manage. Some treatment options include inhalation of 100% oxygen or subcutaneous/intranasal administration of sumatriptan for acute cluster attacks and bridging therapy with oral prednisolone until oral prophylactic therapy is effective. Finally, drugs for the preventive treatment of CH include verapamil, lithium, divalproex sodium (Depakote), gabapentin, and topiramate. Patients suffering from CH should first be encouraged to change potentially harmful lifestyle activities, including smoking or alcohol consumption, especially during cluster periods, to minimize CH episodes as much as possible before initiating acute or prophylactic drug treatment. Cluster headaches (CH) are categorized under trigeminal autonomic headaches. CH is generally treated through acute drug therapy and preventive medicine. These excruciating, unilateral headaches are usually accompanied by conjunctival injections and lacrimation, which involve bursts of moderate to severe burning, piercing, or throbbing pain and occur acutely, episodically, or chronically. Increasing controversy continues to challenge research on CH, especially prophylactic treatment, related to the intensities of CH pain and increased ethical concerns surrounding placebo treatments, making the design of randomized controlled trials difficult. Fortunately, as new technologies and genetic studies emerge, researchers better understand the etiology of CH, allowing for more specific targeted therapies. Therefore, this review discusses divalproex, valproate, and other traditional and novel prophylactic treatment options for CH, comparing their safety profiles, pharmacodynamics, pharmacokinetics, and limitations.