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Pagoclone - disappointing news

Dr Robin Lickley | 01.09.2010

Dr Robin Lickley of Queen Margaret University, Edinburgh gives an update on this drug which has been undergoing trials for stammering.

Though still extremely limited in use, there is now a history of medical treatments "for stammering" going back over 30 years. I put the words "for stammering" in quotes because there is no medical treatment specifically developed or approved to treat stammering - no wonder drug.

To produce an effective drug treatment, one should ideally know what exactly is being treated. There is evidence that stammering is associated with excessive amounts of the neurotransmitter dopamine in the brain. Drugs that have been reported as helping people who stammer include dopamine blockers, like Haloperidol, Olanzapine, Risperidone, Ziprasidone and Molindone, amongst others. These medications have been prescribed for psychosis or schizophrenia and bipolar disorder: None of them have been approved specifically for stammering. Side effects of these drugs can be significant.

Over the past five years, a different kind of drug has been in the stammering news. Pagoclone (a selective GABA-A partial antagonist) was originally developed to reduce social anxiety, though it has never made it to market for that purpose. Clearly, social anxiety has a major role in stammering and early trials treating anxiety also revealed an effect on fluency. Now, Pagoclone has become the first drug to be tested through the American Food and Drug Administration process as a treatment specifically for stammering. As a result, Pagoclone is currently the subject of the largest ever stammering-related clinical drug trial. Aside from the scientific detail, a major advantage of Pagoclone over most of the dopamine blocking medications is that it has relatively few side effects.

Dr Gerald MaguireDr Gerald Maguire, MD, Director of the Kirkup Center for the Medical Treatment of Stuttering at UC Irvine, California, is Principal Investigator on the clinical trial. Dr Maguire was able to report informally on the latest results of the trial at the US National Stuttering Association (NSA) conference in Cleveland, Ohio, in July 2010.

After promising findings at an earlier stage, the trial had moved to Phase IIb, an 8 month double-blind placebo-controlled trial with over 300 participants at about 40 sites in the USA.

The result? As Dr Maguire and Endo Pharmaceutical report, this study did not meet its pre-specified criteria for success. Significant and lasting gains in fluency, according to the trial's criteria, were not forthcoming. However there were some interesting trends, which will be subject to further analysis.

At the NSA conference, and on various internet sites since the announcement, there are impressive and passionate reports from individuals who have been on Pagoclone trials ('open label', i.e. they know they are on the real drug rather than a control), who report that their stammering recedes when on the drug and comes back when off. However, placebo effects can also be impressive.

During his talk at the conference, Dr Maguire linked nicely with recent findings in brain imaging and in genetics, suggesting that maybe at some time in the future, there will be sufficient scientific evidence to support the development of highly targeted medical intervention.

But, for now, the bottom line is that your doctor won't be prescribing the wonder drug for stammering in the near future.

Extended version of article in Autumn 2010 issue of 'Speaking Out', page 4