Valproic Acid Linked with Reduced Risk of Developing Head and Neck Cancer

Sodium valproate is a common mood stabilizer (Photo credit: Wikipedia)

I was surprised to read this press release this morning concerning valproic acid, an antiepileptic, mood stabilizing medication that has also been used traditionally in the management of neuropathic pain.

I am interesting in seeing the doses most commonly encountered and the relevant toxicities. As PCF-4 (PalliativeDrugs.org) notes, no single mode of action accounts for its anti-seizure activity. It is a:

• sodium and T-type calcium channel blocker
• an NMDA receptor-channel blocker (?helpful in hyperalgesia)
• alters GABA (distinctively selective for midbrain), dopamine and serotonin transmission

T-type calcium channels have been implicated in thalamic burst firing (absence seizures), neuropathic pain and possibly in regulating pain excitation thresholds in a 'T-rich' subset of peripheral nociceptors. 

Beneficial effects have been reports in cancer-related neuropathic pain in Europe and Australia, but mixed results in other pain scenarios. Onset of action can often be within 24 hours for neuropathic pain.

But I digress - on to the news of the day:

Excerpt of Press Release via Wiley:

"A new study indicates that a commonly used mood stabilizing drug may help prevent head and neck cancer. The study is published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

Valproic acid (VPA) is currently prescribed as an anti-seizure medication and mood stabilizer, but it is also being studied as an anticancer agent because it inhibits histone acetyl transferases, which help control gene expression by changing DNA structure.

Johann Christoph Brandes MD, PhD, of the Atlanta Veterans Affairs Medical Center and Emory University in Atlanta, led a team that assessed the anticancer effects of VPA in a study of 439,628 veterans, of whom 26,911 were taking the medication for bipolar disorder, post-traumatic stress disorder, migraines, and seizures.

Veterans who took VPA for at least one year had a 34 percent lower risk of developing head and neck cancer compared with those who did not take the medication. Higher doses and longer duration of VPA use seemed to provide additional benefits. No significant differences were observed for lung, bladder, colon, and prostate cancer incidences.

“A 34 percent risk reduction for the development of head and neck cancer with VPA use could result in the prevention of up to approximately 16,000 new cases and 3,000 to 4,000 annual deaths in the US alone,” said Dr. Brandes. “Head and neck cancer is an important global health crisis, and low cost and low toxicity prevention strategies like VPA use have a high potential impact on pain, suffering, costs, and mortality associated with this disease.”

Article: “Long-term use of valproic acid in United States Veterans associates with reduced risk of smoking related head-and neck cancer.” Hyunseok Kang, Theresa Gillespie, Michael Goodman, Seth Brodie, Mina Brandes, Maria Ribeiro, Suresh Ramalingam, Dong Shin, Fadlo Khuri, and Johann Christoph Brandes. CANCER; Published Online: March 24, 2014 (DOI: 10.1002/cncr.28479).

URL Upon Publication: http://doi.wiley.com/10.1002/cncr.28479

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