Patient preferences for ketamine-based antidepressant treatments in treatment-resistant depression: Results from a clinical trial and panel

Abstract

BackgroundNovel ketamine-based pharmacotherapies can reduce depressive symptoms among patients with treatment-resistant depression (TRD), but associated short-term symptoms and potential adverse events raise complex benefit-risk questions. MethodsA web-based discrete-choice experiment was administered to 161 esketamine-treated TRD subjects participating in the SUSTAIN-2 and SUSTAIN-3 clinical-trials; and to 301 online panel participants. Participants evaluated hypothetical depression treatments defined by varying levels of improvement in depression symptoms; time to response; transient post-dose issues (dissociation, dizziness, monitoring requirements, and driving restrictions); and potential long-term risks of ulcerative cystitis and cognitive impairment previously reported from ketamine abuse. ResultsThe clinical-trial and panel respondents had similar preferences. On average, the 54 % of clinical-trial and 64 % of panel respondents who accepted benefit-risk tradeoffs placed the highest value on improving depression symptoms (relative importance = 10) and the least importance on avoiding transient post-dose issues (relative importance <3). Clinical-trial respondents were willing to accept risks of permanent cognitive impairment up to 4.7 % [95 % CI: 3.5 % – >5.0 %] or ulcerative cystitis higher than the survey’s maximum 5 % level to improve their depression symptoms from MADRS-40 (severe) equivalent to MADRS-20 (moderate) equivalent; panel respondents accepted somewhat lower risks (P>.05). ConclusionsMost patients and panelists indicated a willingness to accept significant ulcerative cystitis or cognitive risks to realize improvements in depression, with few differences between samples. Avoiding transient post-dose issues with esketamine was of relatively little concern to most participants.