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.
Amitriptyline; Analgesics, Non-Narcotic; Cytochrome P-450 CYP2D6; Diabetic Neuropathies; Genotype; Humans; Pilot Projects; Random Allocation; Treatment Outcome
CYP2D6; activity score; adverse drug reactions; amitriptyline; diabetic neuropathy
Chaudhry M, Alessandrini M, Rademan J, et al. Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study. Pharmacogenomics. 2017;18(5):433-443. doi:10.2217/pgs-2016-0185