Further Drug Research

Dr. McGuire, UC Irvine, sent the following communication:

Endo Pharmaceuticals is still analyzing the Pagoclone IIb results and my co-investigators and I will seek publication of the data once fully analyzed. As you know, we did publish the Phase II study in the Journal of Clinical Psychopharmacology earlier this year. Also, my colleagues and I at UC Irvine will be starting a trial of asenapine for stuttering in the coming months. We have other compounds for stuttering in our pipeline development as well. Fortunately, multiple studies investigating dopamine antagonists in stuttering (e.g. haloperidol, risperidone, olanzapine) have yielded positive efficacy. Newer generation dopamine blocking agents such as asenapine and others have fewer side-effects than their predecessors and we are very excited to begin this new chapter in stuttering pharmacotherapy research.
Again, I want to thank the author of this blog for providing this forum for discussion.

We look forward to the publication of the phase IIb pagoclone trials. It is also good to hear that exploratory research is being conducted to identify other drugs that may improve fluency. We realize that therapeutic drug testing is a long and tedious process. This testing may be even more difficult in the case of stuttering because the mind plays an important role in determining outcomes which makes separating genuine effects from placebo effects challenging.

Asenapine is a member of the class of atypical antipsychotics and, as such, acts directly to block dopamine activity. It is claimed that users of asenapine have less weight gain and a reduced risk of developing diabetes, so this drug may be marginally better than Zyprexa or Abilify in that regard. However,much like with the other atypical antipsychotics, anecdotal reports indicate that some users taking this drug feel "zoned out," "zombie-like," and "groggy."
One problem with virtually all neurotransmitter drugs is that they lack selectivity with regard to the areas of the brain that they affect. Dopamine antagonists not only inhibit dopaminergic activity in the motor neuron section of the brain (which is good for improving fluency) but also in other areas of the brain which may lead to other unwanted or adverse effects. At this point in time, no obvious mechanisms for targeting a specific brain area are apparent, but this would be an interesting area for further research.

It might also be interesting to administer multiple drugs at the same time. For example, a weaker dose of an atypical antipsychotic coupled with a dose of gabapentin or pregabalin would have the effect of depressing the dopaminergic system while enhancing GABAergic activity. A potential advantage of multiple drug therapy might be that the negative aspects of a stronger dosage of a single drug may be avoided. Of course, the possibility of adverse drug interactions would need to be taken into account when using multiple drugs.

In a shortly upcoming post, we will put forth some speculations on the neurobiological basis of the mind as it affects stuttering.