Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant

This study (n=60) of randomized, placebo-controlled, crossover clinical trials appraises suicidal ideation (SI) with ketamine infusion in persons with treatment-resistant depression (TRD). The results indicated improvement in suicidal thoughts after ketamine infusion and the measures are sensitive to these changes.

Abstract

“Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days. Assessments were compared using correlational analyses and effect sizes at 230 min and three days after ketamine infusion. Linear mixed models evaluated change in ideation across all time points. The HAM-D and MADRS suicide items demonstrated correlations of r > .80 with the first five items of the SSI (SSI5). On linear mixed models, an effect for ketamine was found for the HAM-D, MADRS, BDI items, and SSI5 (p < .001), but not for the full SSI (p = .88), which suggests a limited ability to assess change over time in patients with low levels of suicidal thoughts. Taken together, the results suggest that repeated suicidal assessments over minutes to days appear to detect improvement in suicidal thoughts after ketamine infusion compared to placebo. The MADRS suicide item, BDI suicide item, and SSI5 may be particularly sensitive to rapid changes in suicidal thoughts.“

Authors: Elizabeth D. Ballard, David A. Luckenbaugh, Erica M. Richards, Tessa L. Walls, Nancy E. Brutsché, Rezvan Ameli, Mark J. Niciu, Jennifer L. Vande Voort & Carlos A. Zarate Jr.