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Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot
Mamoonah Chaudhry1, Marco Alessandrini1, Jacobus Rademan1,2
1Department of Immunology & the Institute for Cellular & Molecular Medicine, South African Medical Research Council Extramural Unit for Stem Cell Research & Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Aim:
Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.
Method:
To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.
Results:
Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.
Conclusion:
Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.
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