Pharmacogenetic Testing

Many patients with Grade III dysautonomia require multiple medications for treatment.

They often come after having failed or reacted poorly to a long list of medications in the past. I have come to rely very much on pharmacogenetic testing to inform on why a patient may not have tolerated a medication well and how to best select medications as they launch into what is likely to be polypharmacy.

This testing can be performed very rapidly by the Mayo Clinic. See the laboratory section in the addendum for a typical lab requisition. Once results are returned, a pharmacogenomic/Drug Matrix can be assembled and this gives some guidance on which medications to avoid, which to attenuate dosage, which to push further dosage, and which might be used strategically to enhance or inhibit the degradation of another medication.

drug-matrix

Example of a Pharmacogenetic/Drug Matrix showing the results of this patient’s CYP and Serotonin Receptor and Transporter profile. Based on these results, this patient should not have any detectable issues with fludrocortisone, guanfacine, Lyrica or Wellbutrin. Midodrine and ondansetron are expected to be rapidly metabolized by CYP2D6 which is heterozygous for a copy of gene known to have rapid metabolism. This does not mean they will not be useful for this patient but they likely will require higher and more frequent doses than usual. This bore out to be true for this patient that found midodrine at 10mg four times daily gave the most benefit. This matrix also informs that Concerta might be the better choice over Adderall should that class of drug be considered. This patient did not respond well to Prozac and these findings inform why that is so. Not only is Prozac rapidly metabolized but both the serotonin transporter and A2/C2 receptor are not favorable for SSRI use. The same would be true of the other SSRIs present. This made Wellbutrin the obvious choice. Wellbutrin has the added benefit of inhibiting CYP2D6 allowing midodrine, and if needed, metoprolol, more favorable metabolism.

 

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