Abstract
To the Editors,
We read with great interest the recent randomized controlled trial by Cao et al., 1 which evaluates the safety and efficacy of mirtazapine in functional dyspepsia (FD) patients who had poor outcomes with traditional treatments. We commend the authors for conducting this important study that highlights the potential of mirtazapine in reducing the overall severity of symptoms of dyspepsia. However, we would like to seek clarification on a few aspects of the study.
The single randomization design of the study raises concerns, as it remains unclear whether allocation concealment was ensured. Lack of proper concealment may introduce selection bias, potentially affecting the reliability of the findings. A double-blind design would have mitigated this risk and strengthened the internal validity of the study. Furthermore, the control group did not receive an active comparator or placebo; instead, mirtazapine was added to standard therapy. This design makes it difficult to isolate the independent effect of mirtazapine, as improvements observed in the intervention group could be influenced by placebo effects, expectancy bias, or synergistic interactions with standard treatments. A placebo-controlled or head-to-head comparator trial would have provided a more robust evaluation of mirtazapine’s efficacy.
The study does not specify the randomization method (e.g., computer-generated or block randomization). In addition, it provided baseline characteristics such as age and sex; however, other characteristics like symptom severity, anxiety levels, or comorbidities were not presented. If the groups were not well-matched at baseline, the observed effects could be attributed to pre-existing differences rather than the effect of mirtazapine.
Although the study used validated tools (e.g., Nepean Dyspepsia Index, Visceral Sensitivity Index) to assess outcomes, symptom relief and quality of life are inherently subjective measures. These outcomes may have been influenced by expectation bias, particularly if patients were aware of their treatment assignments. The mirtazapine group showed significant symptom improvement (p < 0.001), along with enhancements in quality of life and anxiety levels. However, the effect size and clinical relevance remain unclear, as the study did not report confidence intervals or relative risk reduction.
In addition, given the strong influence of psychological factors on FD, it remains unclear whether the efficacy of mirtazapine is due to its anxiolytic effects rather than a direct action on gastrointestinal function. While the study recorded adverse events, details were limited. Weight gain could be a concern, especially for patients with metabolic conditions. Follow-up data on whether weight gain persisted beyond the 8-week period is missing, making it difficult to assess potential risks associated with extended use.
Mirtazapine shows promise for FD treatment but should be used cautiously. The absence of long-term follow-up beyond 8 weeks raises concerns about the sustainability and safety of mirtazapine in FD management especially when used for an extended period. Future studies should ensure better blinding, placebo control, and longer follow-up to confirm findings and elucidate their clinical implications.
