A NOVEL EXTENDED-RELEASE TRIAL OF KETAMINE ORAL TABLET FOR REFRACTORY NEUROPATHIC PAIN IN DIABETIC NEUROPATHY: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Abstract

Background: Painful diabetic neuropathy is a common and disabling complication of diabetes mellitus, often resulting in persistent neuropathic pain that is difficult to control with standard pharmacological therapies. A substantial proportion of patients continue to experience significant symptoms despite optimized treatment, highlighting the need for novel therapeutic strategies with alternative mechanisms of action and improved tolerability for long-term use.

Objective: To evaluate the safety, tolerability, and efficacy of a novel extended-release oral ketamine formulation in reducing neuropathic pain intensity among patients with refractory diabetic neuropathy.

Methods: A randomized, placebo-controlled trial was conducted in an urban healthcare setting over four months. Adults with confirmed diabetic neuropathy and persistent pain despite standard therapy were randomly assigned to receive either extended-release oral ketamine or placebo in addition to stable background treatment. Pain intensity, neuropathic pain characteristics, and quality of life were assessed at baseline and during follow-up using validated instruments. Safety and tolerability were evaluated through adverse event monitoring and clinical assessments. Between-group comparisons were performed using appropriate parametric statistical tests.

Results: Sixty participants were randomized, with a high study completion rate. The ketamine group demonstrated a significantly greater reduction in mean pain scores compared with placebo, alongside marked improvements in neuropathic pain characteristics and quality-of-life measures. Pain reduction was progressive and sustained throughout the study period. The intervention was generally well tolerated, with mostly mild and transient adverse events and no serious safety concerns observed.

Conclusion: Extended-release oral ketamine was associated with meaningful analgesic benefit and acceptable tolerability in patients with refractory diabetic neuropathic pain. These findings suggested that pharmacokinetically optimized ketamine may represent a valuable adjunctive option for this challenging clinical population.