Effects of Agomelatine on Sleep Quality, Anxiety, Depression, Appetite, and Fatigue During Hematopoietic Stem Cell Transplantation: A Triple-Blind, Placebo-Controlled Clinical Trial

Abstract

Background: Sleep disturbances, anxiety, depression, reduced appetite, and fatigue are common among patients undergoing hematopoietic stem cell transplantation (HSCT) and can adversely affect quality of life and recovery. Objectives: This study aimed to evaluate the effects of agomelatine on sleep quality, anxiety, depression, appetite, and fatigue in patients undergoing HSCT. Methods: In this clinical trial, 165 candidates were screened, and 90 patients undergoing HSCT were randomly assigned using block randomization to receive agomelatine 25 mg nightly or a matching placebo throughout hospitalization, which lasted approximately 1 month. Outcomes were assessed at admission, during the neutropenic phase, and at discharge using the Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale, Brief Fatigue Inventory, and Council on Nutrition Appetite Questionnaire. Analyses were performed using STATA version 17, with a significance threshold of P < 0.05. Results: Crude group comparisons showed favorable trends in global PSQI score and its components, anxiety, depression, and appetite with agomelatine relative to placebo; most differences were not statistically significant. Fatigue showed no significant overall between-group benefit, although scores changed over time. Group-by-time interactions were statistically significant. Mean changes in PSQI component scores were lower with agomelatine across the 3 assessment periods. In particular, the mean change in the PSQI sleep-medication component score was approximately 0.5 units lower with agomelatine than with placebo (β = -0.49; 95% CI, -0.90 to -0.09; P = 0.016). No statistically significant between-group difference in reported adverse events was observed. Conclusions: Agomelatine may have a supportive role during HSCT, particularly in relation to a lower PSQI sleep-medication component score. The negative crude coefficient for the global PSQI score also favored agomelatine, although this comparison was not statistically significant. Reported adverse events did not differ significantly between groups. Larger trials, including trials evaluating a higher dose, are required to confirm treatment effects on sleep and psychological outcomes.