Subgroups and Drug Testing Trials

The existence of subgroups among stutterers may lead to the appearance of reduced efficacies for any therapeutic treatment under test.  For example, some stutterers may respond to dopamine blockers such as atypical antipsychotic drugs while others may respond to dopamine agonists such as amphetamines.  Including both of these subgroups within a drug testing trial will lead to reported results that are less robust.

In other areas of medical research, attempts have been made to identify individuals for inclusion in drug trials based on some measurable characteristic.  For example, researchers have identified certain genetic traits among breast cancer victims on the basis of which these individuals may have a greater chance of success in the trials.

With regard to stuttering, the level of knowledge has not yet reached the stage whereby  subgroups can be identified on the basis of genetic analyses.  However, there may be other means for identifying subgroups.

For example, in selecting individuals for a trial of a dopamine antagonist such as an atypical antipsychotic, a pretrial might be conducted to choose individuals on the basis of their responses to a benzodiazepine (BZ).  BZs effectively block dopamine by indirect means, so that an individual whose fluency improves on a BZ might be in the same subgroup responsive to an atypical antipsychotic.  The effect of the BZ on fluency should be apparent within half an hour after administration.  On the other hand, an individual whose fluency either deteriorates on BZs or remains the same might be in the amphetamine responsive group (or in a potentially third subgroup responsive to neither treatment protocol).

We can additionally refine this selection approach by further screening for individuals who may be particularly responsive to placebos.  During the pretrial, a subject might be given a BZ on one day and a placebo on another.  An individual who responds positively to both the BZ and the placebo would be eliminated as a trial subject.

The approach outlined above is by no means perfect.  BZs affect the limbic system (involving emotions) more strongly than atypical antipsychotics.  Since the limbic system (via the ventral striatum) may affect fluency (see the “An Anxious Mind Affects Stuttering” posts), the drug trial group chosen by the above approach may still contain individuals (i.e., false positives) who are not responsive to dopamine antagonists.

The pretrial/trial approach may give a more accurate measure of the effect of a drug on a particular subgroup.