Boadie W. Dunlop
The six-item Hamilton Depression Rating Scale, or HAM-D6, was a better measure of core depressive symptoms than the 17-item HAM-D17, according to results of a post hoc analysis of a randomized controlled trial published in BMC Psychiatry.
“This study provides more evidence that a depression rating scale such as the HAM-D6 that focuses on core symptoms of major depression has greater sensitivity for detecting differences between treatments than does the traditional longer rating scale, the HAM-D17, which includes several peripheral symptoms (eg, weight change, loss of libido, sleep changes) which may be related to medication side effects or other psychiatric or medical problems,” Boadie W. Dunlop, MD, MS, of the department of psychiatry and behavioral sciences at Emory University School of Medicine, told Healio Psychiatry. “By using the HAM-D6 to focus on change in the core depressive symptoms (eg, depressed mood, guilt, anhedonia/motivation, psychomotor retardation, psychic anxiety and low energy) instead of the entire HAM-D17, a statistically significant benefit of using pharmacogenomic testing to inform antidepressant medication selection was detected.”
According to Dunlop and colleagues, the HAM-D is the most widely used outcome measure in major depressive disorder clinical trials. However, researchers raised concerns over the past 4 decades about HAM-D17’s ability to accurately to assess change in and severity of depression symptoms. Thus, a more focused version of the scale — HAM-D6 — came to be a widely used subscale.
Prior to the present study, it was unknown whether HAM-D6 showed greater sensitivity when comparing two active MDD treatment arms. To address this research gap, Dunlop and colleagues used data from 1,541 patients in the intent-to-treat cohort of the Genomics Used to Improve DEpression Decisions (GUIDED) trial — a randomized controlled trial in which both raters and patients were blinded and combinatorial pharmacogenomics-guided care was compared with treatment as usual in patients with MDD. They used the HAM-D6 and HAM-D17 scales to evaluate percent of symptom improvement, remission rate and response rate from baseline to week 8.
The researchers found that when the HAM-D6 was used as the continuous measure of symptom improvement, the guided-care arm demonstrated a statistically significant benefit over treatment as usual at week 8, but they did not find this outcome when using the HAM-D17, they noted. Guided-care response rates increased significantly compared with treatment as usual when evaluated with both scales, and remission rates were significantly greater for guided-care using both measures. Guided-care patients who at baseline were taking medications predicted to have gene-drug interactions exhibited further increased benefit over treatment as usual at week 8 for symptom improvement, remission and response using HAM-D6. Through week 24, all outcomes showed continued improvement, and the researchers used Mokken scale analysis to demonstrate the homogeneity and unidimensionality of HAM-D6 across treatment arms, but not of HAM-D17, they wrote.
“Most importantly, the greater sensitivity of the HAM-D6 has implications for personalized medicine approaches beyond pharmacogenomic testing,” Dunlop said. “In developing personalized medicine treatments, we need to be comparing two or more active treatments, not simply an active treatment vs. placebo. Because differences between active treatments are smaller than between active and placebo treatments, it is of great importance that clinical trials use outcome measures that are the most sensitive to detect treatment effects.” – by Joe Gramigna
Disclosures: Dunlop reports research support from Acadia, Assurex Health, Axsome, Janssen and Takeda, consulting work for Assurex Health and Aptinyx, as well as consulting work for Myriad Neuroscience, which sponsored the GUIDED trial. Please see the study for all other authors’ relevant financial disclosures.