Placebo and nocebo responses in painful diabetic neuropathy: systematic review and meta-analysis (P9-6.002)

Abstract

<h3>Objective:</h3> The present study examined both the magnitude of placebo and nocebo responses and the factors contributing to placebo response in randomized, double-blind, placebo-controlled clinical trials of painful diabetic neuropathy (PDN) that: i) had parallel group design, ii) were conducted over the past twenty years, iii) were aimed at evaluating the efficacy of oral medications recommended for the treatment of neuropathic pain and, more specifically, PDN. <h3>Background:</h3> Systematic reviews over last decade support the hypothesis that a relevant part of patients’ response to PDN treatments may be due to nonspecific drug effects. <h3>Design/Methods:</h3> Electronic databases PubMed, Cochrane Controlled Trial Register, EMBASE, and Scopus were searched from January 2000 to December 2020, without any restriction of countries. The protocol was registered a priori on the international Prospective Register for Systematic Reviews (PROSPERO) under the ID CRD42021223379. <h3>Results:</h3> In the eligible 20 studies (2,302 patients in the placebo arms) the magnitude of placebo and nocebo responses was comparable to previous literature. The overall mean pooled placebo response was −1.56 change in pain intensity from baseline [95% CI: −1.54, −1.58], with a mean Cohens’ d effect size of 0.73, while the pooled placebo 50% Response Rate was 25.3% (from 21.7% to 29.0%). The overall percentage of patients with adverse events (AEs) in the placebo arms was 27.2% [95% CI: 25.4%, 28.9%], while the overall percentage of patients dropping out due to AEs was 5.1% [95% CI: 4.2%, 6.0%]. Regarding possible moderators, the year of study initiation confirmed to be significantly associated with placebo response, whereby more recent — and thus longer and bigger — trials showed higher placebo response −0.06 [95% CI: −0.10, −0.02, P=0.008]. Neither trail design nor demographic and baseline characteristics showed significant effects on placebo response. <h3>Conclusions:</h3> This knowledge would benefit clinical trials, clinical practice, and placebo research. <b>Disclosure:</b> Dr. Frisaldi has received publishing royalties from a publication relating to health care. Dr. Vollert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Casquar. Dr. Vollert has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Embody Orthopedics . Dr. Vollert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmaceuticals. Husam Al Sultani has nothing to disclose. Ms. Hafuth has nothing to disclose. Prof. Benedetti has nothing to disclose. Dr. Shaibani has nothing to disclose.