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Randomized Controlled Trial
. 2024 Oct:340:116105.
doi: 10.1016/j.psychres.2024.116105. Epub 2024 Aug 3.

Enrichment using speech latencies improves treatment effect size in a clinical trial of bipolar depression

Joshua S Siegel  1 , Alex S Cohen  2 , Steven T Szabo  3 , Sasagu Tomioka  3 , Mark Opler  4 , Brian Kirkpatrick  5 , Seth Hopkins  3
Affiliations
Randomized Controlled Trial

Enrichment using speech latencies improves treatment effect size in a clinical trial of bipolar depression

Joshua S Siegel et al. Psychiatry Res. 2024 Oct.

Abstract

Clinical trials in depression lack objective measures. Speech latencies are an objective measure of psychomotor slowing with face validity and empirical support. 'Turn latency' is the response time between speakers. Retrospective analysis was carried-out on the utility of turn latencies as an enrichment tool in a clinical trial of bipolar I depression. Speech data was obtained from 274 participants during 1,352 Montgomery-Åsberg Depression Rating Scale (MADRS) recordings in a randomized, placebo controlled, 6-week clinical trial of SEP-4199 (200 mg or 400 mg). Post-randomization turn latencies were compared between patients with moderate to severe depression and patients whose depression had remitted. A cutoff was determined and applied to turn latencies pre-randomization to classify individuals into two groups: Speech Latencies Slow (SL-Slow) and Speech Latencies Normal (SL-Normal). At week 6, SL-Slow (N = 172) showed significant separation in MADRS scores between placebo and treatment arms. SL-Normal (N = 102) showed larger MADRS improvements and no significant separation between placebo and treatment arms. Excluding SL-Normal increased primary outcome effect size by 52 % and 100 % for the treatment arms. Turn latencies are an objective measure available from standard clinical assessments and may assess the severity of symptoms more accurately and screen out placebo responders.

Keywords: Biomarker; Depression; Digital phenotyping; Enrichment; Interview; Language; Latency; Psychomotor; Speech.

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Conflict of interest statement

Declaration of competing interest This project reflects a collaboration by Sumitomo Pharma America, Inc, Quantic Innovation, WCG Inc., Louisiana State University, and the Psychiatric Research Institute at the University of Arkansas for Medical Sciences. Potential conflicts of interest between private and academic interests were formally reviewed and mitigated by an LSU review board. Potential conflicts of interest were addressed by transparent declaration of potentially competing interests, and by publishing these results such that the scientific community might be able to critically review, replicate and extend them. S.M, S.T.S, S.T., A.O., K.S.K, D.P. and S.H. are employees of Sumitomo Pharma America Inc. M.O. is a full-time employee and shareholder in WCG. In the past three years, A.S.C has received honoraria/support from Indivior and Boehringer Ingelheim. A.S.C., B.K., and M.O. have stock or related interests in Quantic Innovation which develops and validates digital health measurements. B.K receives licensing royalties from ProPhase for use of the Brief Negative Symptom Scale (BNSS) by for-profit groups; these fees are donated to the Brain and Behavior Research Foundation. In the last three years he has also received honoraria and travel support from ProPhase for training pharmaceutical company raters on the BNSS; consulting fees and/or travel support from Lundbeck, Acadia, ProPhase, Otsuka, and Minerva Neurosciences; fees from anonymized investors through Guideposts and Decision Resources Group; and an honorarium from Otsuka for preparation of educational materials.

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