Mirtazapine for the treatment of irritable bowel syndrome: A systematic review

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and altered bowel habits, with types classified based on stool patterns: (1) Diarrhea-predominant IBS (IBS-D); (2) IBS with constipation (IBS-C); and (3) Mixed IBS. This condition affects approximately 10% of adults globally and is challenging to treat due to the lack of definitive structural or biochemical markers. Treatment options include dietary, pharmacological, and psychological therapies, yet patients often struggle with refractory symptoms impacting quality of life (QoL).

AIM

To review existing literature to evaluate Mirtazapine’s effectiveness in treating IBS, particularly in older patients.

METHODS

This review as registered in the PROSPERO database (CRD420251022721) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic review was conducted between February 2024 and March 2024, searching PubMed, EMBASE, and BMJ Case Reports from database inception to present. We included English-language randomized controlled trials (RCTs), prospective clinical studies, and case reports of adult IBS-D or IBS-C patients treated with Mirtazapine, reporting on symptom resolution, abdominal pain, insomnia, or related outcomes. Data extraction covered study design, sample size, dosage, duration, and outcomes. No meta-analysis was performed due to heterogeneity.

RESULTS

Of 77 identified references, five publications met inclusion criteria: (1) Three case reports; (2) One double-blind RCT (n = 67; Mirtazapine vs placebo); and (3) One prospective study (n = 116 with comorbid depression, 50 on Mirtazapine). The RCT demonstrated significant reductions in IBS symptoms severity score, diary-based symptoms (abdominal pain, urgency, frequency; all significant except bloating), and improved QoL and anxiety scores. Case reports (patients aged 35–66 years) reported normalization of stool frequency, weight gain, and relief of anxiety/depressive symptoms. The prospective study found baseline sleep disturbance correlated with improvements in pain and diarrhea.

CONCLUSION

Although evidence is limited, current data indicate Mirtazapine improves IBS-related symptoms and associated mental health issues, with rapid onset and good tolerability. The small number of studies and absence of large-scale RCTs warrant cautious interpretation. Further RCTs are essential to confirm Mirtazapine’s role in IBS treatment and define optimal patient profiles.

Keywords: Irritable bowel syndrome; Mirtazapine; Antidepressants; Quality of Life; Rome criteria

Core Tip: This study highlights the potential of mirtazapine in treating refractory irritable bowel syndrome (IBS), particularly diarrhea-predominant IBS with comorbid depression. By integrating a systematic review with a detailed case report, our findings demonstrate that mirtazapine, combined with Rifaximin, a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet, and probiotics, significantly improves patient outcomes. This work emphasizes the importance of thorough diagnostic evaluation in IBS and supports further randomized controlled trials to confirm mirtazapine's efficacy.