Although antidepressant trials typically use weekly ratings to examine changes in symptoms over six to 12 weeks, antidepressant treatments may improve symptoms more quickly. Thus, rating scales must be adapted to capture changes over shorter intervals. We examined the use of the 17-item Hamilton Depression Rating Scale (HDRS) to evaluate more rapid changes. Data were examined from 58 patients with major depressive disorder or bipolar disorder enrolled in double-blind, placebo-controlled, crossover studies who received a single infusion of ketamine (0.5 mg/kg) or placebo over 40 min then crossed over to the other condition. HDRS subscales, a single HDRS Depressed mood item, and a visual analogue scale were used at baseline, after a brief interval (230 min), and one week post-infusion. Effect sizes for the ketamine-placebo difference were moderate (d > 0.50), but one and two-item HDRS subscales had the smallest effects. Response rates on active drug were lowest for the complete HDRS (43%); the remaining scales had higher response rates to active drug, but the shortest subscales had higher response rates to placebo. Correlations between the changes from baseline to 230 min post-ketamine across scores were similar for most subscales (r = 0.82-0.97), but correlations using the single items were lower (r < 0.74). Overall, effect sizes for drug-placebo differences and correlations between changes were lower for one- and two-item measures. Response rates were lower with the full HDRS scale. The data suggest that, to best identify rapid antidepressant effects, a scale should have more than two items, but fewer items than a full scale.
Trial registration: ClinicalTrials.gov NCT00088699.
Keywords: Antidepressant; Bipolar disorder; Depression; HDRS; Ketamine; Ratings.
Published by Elsevier Ltd.