Safety Implications of Low-Dose Amitriptyline in Neuropathic Pain

Background: Treatment guidelines in neuropathic pain list amitriptyline as a first-line option. Modest evidence on efficacy and safety concerns possibly shape the rationale behind dosing recommendations. An observational study was carried out to understand the usefulness of safety monitoring for this established medicine. Methods: Twenty-six (26) subjects were categorized into 2 groups: 13 patients under pain management receiving 10 mg amitriptyline daily for less than 12 months, and 13 patients under psychiatric care receiving a daily dose of 25–75 mg for over 12 months. Dose-related reference ranges were calculated and blood levels were assessed for the case examples presented. Adverse events and ECGs were collated. QT intervals were corrected using Bazett’s and Fridericia’s formulae. Side-effect frequencies were evaluated both within the research groups, and in the broader perspective of spontaneous ADR reporting through EudraVigilance. Results: The applicability of dose-related reference ranges, considering confounding factors such as drug interactions and metabolizer status, is discussed. Patients in both groups reported on average three side-effects, with drowsiness being reported more significantly in the 10 mg group and possibly attenuating with time; an observation not replicated for dry mouth. ADR reports with non-granulated information limit the usefulness of the data retrieved. Comparison of QT corrected with Bazett’s and Fridericia’s formulae suggests that Bazett’s may overestimate the number of patients on amitriptyline with QTc prolongation. Conclusions: This research supports the adoption of evolving research observations to understand the implications of dosing recommendations and safety assessments in attempt of delivering individualized treatment with minimal risk