Thinking Out of the Pillbox: The Relevance to Topiceuticals in the Treatment ofNeuropathic Pain

Topiceuticals can be defined as specialized pharmaceutical formulations containing topically applied drugs. Topiceutical analgesics need to be differentiated from transdermal formulations of analgesics. The latter formulations are specially designed for the active pharmaceutical ingredient to penetrate all skin structures and to generate measurable plasma levels of the formulated analgesic, such as in fentanyl plasters and topical NSAIDs. Its mechanism of actions is thus based on the systemic drug-effects and the formulations act merely as controlled release reservoirs. Topiceutical analgesics however are characterized by local analgesic effects in the absence of systemic effects, such as lidocaine and capsaicin plasters. Lidocaine and capsaicin plasters however have a number of drawbacks based on low convenience of use and local side-effects, reducing patient compliance. Topiceutical analgesics based on compounded creams should not cause such compliance issues and might become valuable new treatments for neuropathic pain. Topical compounded creams deserve a place in the modern armamentarium of the pain physician, once certain key issues such as optimal formulation and concentration are solved. We will discuss some key issues related to Topiceuticals and also present an individualized procedure to quickly differentiate responders from non-responders to topical creams. This procedure might also be helpful to evaluate efficacy and safety in a more practical way compared to full powered randomized placebo controlled trials and might expedite phase II (dose-finding) development.