Provocative induction of psychogenic nonepileptic seizures: Noninferiority of an induction technique without versus with placebo

Abstract

We aim to demonstrate, in a sufficiently powered and standardized study, that the success rate of inducing psychogenic nonepileptic seizures (PNES) without placebo (saline infusion) is noninferior to induction with placebo. The clinical data of 170 consecutive patients with suspected PNES who underwent induction with placebo from January 21, 2009 to March 31, 2013 were pair-matched with 170 consecutive patients with suspected PNES who underwent the same induction technique but without addition of placebo from April 1, 2013 to February 7, 2018 at the same center. The success rates of induction were 79.4% (135/170) without placebo and 73.5% (125/170) with placebo. The difference of these two proportions was 5.9%, with two-sided 95% confidence interval ranging from −3.6% to 15.2%, indicating a non–statistically significant difference. The lower bound of the 95% confidence interval (−3.6%) was above the noninferiority margin (δ = −5%), hence inferring noninferiority of induction without versus with placebo. The greater cumulative induction experiences of the clinician performer (influencing the manner/presentation of induction) may supplant the potential advantage from addition of placebo (the means utilized). Among experienced performers, provocative induction without placebo should be the preferred diagnostic approach, given more ethically acceptable transparency and the noninferior success rate when compared to the same induction technique with placebo.