Diabetes is a serious public health issue, and is projected to be the seventh leading cause of death worldwide by 2030. In the sub-Saharan African region, it is estimated that nearly 1 in 10 people suffer from diabetes, according to the World Health Organization Global Report on Diabetes (WHO, 2016). In the United States, we see similar statistics. The CDC reported in 2014 that nearly 1 in every 11 people in the U.S. are diagnosed with diabetes, accounting for nearly 29.1 million people (Centers for Disease Control and Prevention, 2014 National Diabetes Statistics Report).
Complications can arise in those with diabetes and therefore, proper medication therapy is crucial.
Diabetic Peripheral Neuropathy (DPN) is the most common complication of diabetes and occurs in up to half of diabetic patients, according to a recent study in Pharmacogenomics (Chaudhry et al., April 2017).
The most common symptoms of diabetic neuropathy are increased pain sensitivity, numbness and spontaneous pain in the limbs. Patients frequently describe the pain as burning and shooting.
Amitriptyline: The Drug of Choice for DPN in Developing Countries
Since there are currently no treatments available to completely restore nerve function, drug therapy is often aimed at managing the pain. Antidepressants in particular, specifically amitriptyline, are often used to treat DPN.
This Pharmacogenomics study investigated the use of amitriptyline for DPN in a South African population. Amitriptyline is used to treat the DPN pain due to its numbing effect on the nerves. It is regarded as the drug of choice to for painful peripheral neuropathy in this population given its cost effectiveness.
Genetics Influence How You’ll React to Medications
Common side effects of amitriptyline include blurred vision, drowsiness, constipation, urinary retention and dryness of mouth/eyes. More serious side effects include build-up of metabolic toxins in the heart or the nervous system.
Genetics play a major role in how the body metabolizes medications. Amitriptyline is mainly metabolized in the liver and cleared by the kidneys. How one’s body metabolizes this medication in encoded by two specific genes and one of these genes is responsible for adverse drug reactions (ADRs).
In the case of amitriptyline, patients who are “slow metabolizers” will experience adverse reactions. Patients who are “fast metabolizers” do not experience these adverse reactions. However, since these fast metabolizers clear the drug from their bodies so quickly, they are at risk for not benefiting from treatment.
Study Calls for Pharmacogenetic Screening in Amitriptyline Therapy
The study concluded that pharmacogenetic testing might be useful for tailoring treatment and thereby improving amitriptyline effectiveness. Chaudhry et al. noted that if a patient is a non-responder to amitriptyline, or experiences severe side effects, pre-emptive genetic screening can be performed so an alternative medication may be considered, or the dose adjusted appropriately.
“Our findings…support the use of pharmacogenetic testing in the context of amitriptyline therapy for the management of diabetic pain,” the authors stated, adding that PGx testing can be “valuable to guide drug choice and dosage and thereby improve treatment outcomes in patients with DPN.”