Wednesday, December 28, 2005

Riluzole: Incipient Anxiolytic?

I've written about riluzole before (1 2), because of preliminary evidence that it might be effective for treatment of depression and obsessive-compulsive disorder.  Riluzole is a presynaptic glutamate release inhibitor, approved by the US Food and Drug Administration for the treatment of amyotrophic lateral sclerosis.  It is marketed by Aventis under the brand name, Rilutek.  

Now comes another preliminary study that shows a possible benefit for generalized anxiety disorder.  The study also indicated the drug could have an antipanic effect.  
Open-Label Trial of Riluzole in Generalized Anxiety Disorder
Sanjay J. Mathew, M.D., Jonathan M. Amiel, B.S., Jeremy D. Coplan, M.D., Heidi A. Fitterling, B.A., Harold A. Sackeim, Ph.D., and Jack M. Gorman, M.D.

OBJECTIVE: There is a need to identify novel pharmacotherapies for anxiety disorders. The authors examined the safety and efficacy of riluzole, an antiglutamatergic agent, in adult outpatients with generalized anxiety disorder. METHOD: In an 8-week, open-label, fixed-dose study, 18 medically healthy patients with DSM-IV generalized anxiety disorder received treatment with riluzole (100 mg/day) following a 2-week drug-free period. The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) score at endpoint. RESULTS: Twelve of the 15 patients who completed the trial responded positively to riluzole. At 8 weeks, eight of the 15 patients had HAM-A score indicating remission of their anxiety. The median time to response was 2.5 weeks. CONCLUSIONS: Riluzole appears to be an effective, well-tolerated, and rapidly acting anxiolytic medication for some patients with generalized anxiety disorder. Larger, placebo-controlled studies are indicated.
Although the study was not designed to assess the effectiveness of riluzole for panic attacks, a subgroup of patients with comorbid panic disorder did exhibit improvement in panic symptoms.  

The study mentioned here is highly limited, both because of the small number of patients, and because of the open-label design.  The placebo response rate for anxiety disorders tends to be pretty high, so you really need a large, double-blind study to draw any firm conclusions.  

This raises an interesting question.  Since there now are a few preliminary studies with encouraging findings, what is the delay in coming out with a larger, definitive study?  

According to ePocrates, the average wholesale cost of Rilutek is $815.82 for sixty pills, a one-month supply.   That's  a little steep.  The price might by justified if the drug is useful only for ALS, because of the small number of patients.  Aventis has to recoup their investment, and that is hard to do when the number of patients is small.   But if the drug really is effective for common conditions such as depression, panic disorder, and generalized anxiety disorder, it would be hard to justify the cost.

Thus the conundrum: I suspect that the high cost is dampening enthusiasm for more research.  But unless more research is done, it will not be possible to justify prescribing the drug to larger numbers of patients.

Personally, I think it would be good for Aventis to take the plunge and fund more research, even if it does mean that they would then be under pressure to reduce the cost of Rilutek.  After all, if Soj is correct, anxiety disorders are going to become much more common in 2006.