Safety and Efficacy of Mirtazapine Compared to Sertraline in Hemodialysis Patients with Major Depressive Disorder: A Randomized Controlled Clinical Trial

Background: This study aimed to compare the efficacy and tolerability of mirtazapine and sertraline in moderately depressed patients undergoing chronic hemodialysis therapy. Methods: In this double-blind clinical study, 54 hemodialysis patients diagnosed with moderate to severe depression, scoring greater than 18 on the Beck Depression Inventory, version II (BDI-II), were randomly assigned to receive 12 weeks of treatment with either mirtazapine (15mg/day) plus placebo or sertraline (50 mg/day) plus placebo. Efficacy outcomes were assessed by evaluating changes in baseline BDI-II scores, as well as rates of response and remission at weeks 2, 4, 8, and 12 of treatment. The impact of the antidepressant treatment on the patient’s health-related quality of life was also assessed at the end of the treatment phase, with ratings ranging from 0 (the worst impact) to 10 (the best impact). Safety and tolerability of the study medications were monitored using an antidepressant side effect checklist and through spontaneous participant reports. Both efficacy and tolerability analyses were conducted on the intent-to-treat sample. The p-values less than 0.01 based on Bonferroni's multiple-testing correction method were considered statistically significant. Results: The mixed models for repeated measures analysis revealed a significant time effect on depression symptoms (p < 0.001), indicating improvement in both treatment groups over the study period. However, the treatment effect was not significant (p = 0.160), suggesting no overall difference in depressive symptoms between groups. The interaction between time and treatment was significant (p = 0.020), indicating varying changes in depressive symptoms over time between treatment groups. At week two, patients receiving mirtazapine had a lower mean BDI-II score than those receiving sertraline (15.62±5.24 versus 18.92±5.03), but the difference between the groups was not statistically significant (p-value = 0.022). Subsequent assessments at weeks 4, 8, and 12 showed comparable mean BDI-II scores between both treatment groups. Furthermore, at all assessment points, the rate of responders (≥50% reduction in BDI-II total score from baseline) and the rate of remitters (BDI-II total score of <10) were similar between the treatment groups. However, mirtazapine- treated patients scored higher in assessing the overall impact of the treatment on their quality of life compared to the sertraline-treated group (7.40±1.18 versus 6.51±1.15 p-value = 0.007). Regarding safety and tolerability, although there were differences in the pattern of adverse effects between the treatment groups, the proportion of patients experiencing at least one adverse effect and the rate of dropouts were similar between the two groups, indicating comparable tolerability for both medications. Conclusion: Our results suggest that the efficacy and tolerability of mirtazapine are equivalent to those of sertraline in treating moderate depression in hemodialysis patients. However, mirtazapine appears to have a more favorable effect on patients' health-related quality of life compared to sertraline. Trial Registration: The trial was registered at the Iranian Registry of Clinical Trials (https://www. irct.ir/trial/66756, identifier code: IRCT20120215009014N445). Registration date: 2022-11-09.