title: 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 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.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: Elizabeth.Ballard@nih.gov.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ballard
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: luckenbd@mail.nih.gov.
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: erica.richards@nih.gov.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: tessa.walls@nih.gov.
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Walls
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: brutschn@mail.nih.gov.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Brutsché
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: amelir@mail.nih.gov.
authors.forename: Rezvan
authors.initials: R
authors.lastname: Ameli
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: mark.niciu@nih.gov.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: VandeVoort.Jennifer@mayo.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vande Voort
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: zaratec@mail.nih.gov.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D003024:Clozapine / Q000627:therapeutic use; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D005260:Female; D006801:Humans; D007649:Ketamine; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic; D059020:Suicidal Ideation; D013997:Time Factors; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine; D003024:Clozapine
keywords: Assessment; Depression; Ketamine; Psychometrics; Suicidal ideation