CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.

Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.

CYP2D6*4 polymorphism, tramadol treatment and its clinical impact in patients with postherpetic neuralgia.

AIM: The aim of this study was to investigate the associations between the CYP2D6*4 polymorphism, interindividual differences in CYP2D6 activity and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. PATIENTS & METHODS: The study comprised 158 patients (including 78 nonresponders and 80 responders) with PHN who were undergoing analgesic treatment at the Pain Clinic in the Out Patient Department of the University College of Medical Sciences, Guru Teg Bahadur Hospital (New Delhi, India). The numerical rating scale scores were measured at the resting and movement stages; Neuropathic Pain Symptom Inventory scores were evaluated by the treating physician. WHO-brief questionnaire scores for quality of life and adverse drug effects during the time of study were recorded. All samples were analyzed for the CYP2D6*4 polymorphism using the PCR-restriction fragmentation length polymorphism method. RESULTS: The genotype distribution did not vary significantly among different age groups in nonresponders and responders. The CYP2D6*4 polymorphism was significantly associated with lower Neuropathic Pain Symptom Inventory (burning, squeezing stabbing and pressure) scores. The quality-of-life (sociological, psychological and environmental domains) scores correlated with CYP2D6*4 and showed significant results (p < 0.05) using a generalized linear model. No association was found between the physiological domain compared with the CYP2D6*4 allele (p > 0.05). In addition, the homozygous mutated CYP2D6*4 allele was not related to adverse effects of analgesic therapy. CONCLUSION: The CYP2D6*4 polymorphism may not be a predictor for treatment outcome of patients with PHN receiving tramadol. However, further investigation is required to confirm these findings in a larger sample size.