This research study shows that Amitriptyline 4% and ketamine 2% (AmiKet) provides a rational drug combination to conquer the neuropathic pain. It has several positive effects which makes it highly recommended for targeting the peripheral compartment in addition to central sites of action. 

Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option.

This report summarizes both published and unpublished results of clinical trials with cmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favorable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet.

Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. 

Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.