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

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 minutes 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.

Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials

“…Third, acutely suicidal patients were excluded from one of the clinical trials (before medication taper); the results might have differed if the analysis had included patients at imminent suicide risk or who had higher scores on the SSI5. Also, measuring rapid changes in suicidal ideation is a relatively new field; we chose to use the SSI5 because previous analyses by our group had shown increased sensitivity to change over the total SSI (Ballard et al, 2015), but further psychometric validation of scales used in ketamine research are needed. Fourth, the SHAPS does not clearly distinguish between motivational (anticipation) and consummatory (liking) components of anhedonia.…”

“…These items assess measures such as reduced wish to live, wish to die, reasons for living/dying, desire to make a suicide attempt, and passive suicidal thoughts. Because the full SSI was not administered to each participant, only the first five items (SSI5) were included in this analysis, in line with previous analyses suggesting that the use of the abbreviated versus total SSI in clinical trials of treatments such as ketamine may be able to capture rapid changes in symptoms over minutes to hours (Ballard et al, 2015). …”

Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder

“…In addition, the first 5 items of the SSI were included in the analysis, as these items were consistently administered to all participants and because previous analyses found that the SSI5 is particularly sensitive to rapid changes in suicidal thoughts after ketamine administration. 34 …”

Ketamine: A Potential Rapid-Acting Antisuicidal Agent?

“…Moreover, further analysis from the same datasets using a slightly broader definition of SI found ketamine to have significant effects on SI rating on all scales, with the exception of the total score of the SSI, but there were significant effects noted as measured by the abbreviated SSI5 scale. [35] Consistent with the previous reports showing large effects of a single ketamine infusion on SI, a recent study randomizing 30 patients with MDD to ketamine infusion plus escitalopram or saline infusion plus escitalopram at Beijing Chao-Yang Hospital, [36] found the subjects in the ketamine/escitalopram group had lower explicit measures of SI (as measured by Quick Inventory of Depressive Symptomatology [QIDS] SI item) compared to the placebo/escitalopram group from 1 to 72 hr following treatment, with Cohen’s d ranging from 1.05 to 2.24 during this time period. These participants were outpatients and, other than the concomitant initiation of escitalopram on the first treatment day, were free of other psychotropic medication.…”

“…Among patients receiving ketamine, the individual SI items of the MADRS, HDRS, and BDI have been shown to correlate with the abbreviated five-item SSI, but not with the full scale. [35] …”