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

• Published in: Neurology, psychiatry, and brain research Vol. 37; pp. 67 - 78
• Main Authors: Fairchild, Angelyn O., Katz, Eva G., Reed, Shelby D., Johnson, F. Reed, DiBernardo, Allitia, Hough, David, Sing, Jaskaran, Levitan, Bennett
• Format: Journal Article
• Language: English
• Published: Elsevier GmbH 01.09.2020
• Subjects: Benefit-risk; Conjoint analysis; Depression; Ketamine; Patient outcome assessment; Patient preferences; Patient preferences; Patient outcome assessment; Benefit-risk; Depression; Ketamine; Conjoint analysis
• ISSN: 0941-9500
• DOI: 10.1016/j.npbr.2020.05.003

•In a discrete-choice experiment, most respondents made tradeoffs between improving depressive symptoms, time to response, and potential risks.•Most patients and panelists accepted potential risks of ulcerative cystitis or cognitive impairment to realize improvements in depression.•Respondents with treatment-resistant depression from online panels and clinical trials of esketamine had similar preferences.•Avoiding transient post-dose issues with esketamine was of relatively little concern to most respondents. Novel 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. A 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. The 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). Most 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.